PHAGOCYTOSIS

Phagocytosis is the cellular process of Phagocytes and Protists of engulfing solid particles by the cell membrane to form an internal phagosome, which is a food vacuole, or pteroid. Phagocytosis is a specific form of endocytosis involving the vesicular internalization of solid particles, such as bacteria, and is therefore distinct from other forms of endocytosis such as pinocytosis, the vesicular internalization of various liquids. Phagocytosis is involved in the acquisition of nutrients for some cells, and in the immune system it is a major mechanism used to remove pathogens and cell debris. Bacteria, dead tissue cells, and small mineral particles are all examples of objects that may be phagocytosed.

The process is only homologous to eating at the level of single-celled organisms; in multicellular animals, the process has been adapted to eliminate debris and pathogens, as opposed to taking in fuel for cellular processes, except in the case of the Trichoplax

1. In immune system
Phagocytosis in mammalian immune cells is activated by attachment to Pathogen-associated molecular patterns (PAMPS), which leads to NF-κB activation. Opsonins such as C3b and antibodies can act as attachment sites and aid phagocytosis of pathogens.[1]
Engulfment of material is facilitated by the actin-myosin contractile system. The phagosome of ingested material is then fused with the lysosome, leading to degradation

Degradation can be oxygen-dependent or oxygen-independent.
• Oxygen-dependent degradation depends on NADPH and the production of reactive oxygen species. Hydrogen peroxide and myeloperoxidase activate a halogenating system which leads to the destruction of bacteria.
• Oxygen-independent degradation depends on the release of granules, containing proteolytic enzymes such as defensins, lysozyme and cationic proteins. Other antimicrobial peptides are present in these granules, including lactoferrin which sequesters iron to provide unfavourable growth conditions for bacteria.

It is possible for cells other than dedicated phagocytes (such as dendritic cells) to engage in phagocytosis.[2]

2. In Apoptosis
Following apoptosis, the dying cells need to be taken up into the surrounding tissues by macrophages in a process called Efferocytosis. One of the features of an apoptotic cell is the presentation of a variety of intracellular molecules on the cell surface, such as Calreticulin, Phosphatidylserine (From the inner layer of the plasma membrane), Annexin A1 and oxidised LDL. These molecules are recognised by receptors on the cell surface of the macrophage such as the Phosphatidylserine Receptor, or by soluble (free floating) receptors such as Thrombospondin 1, Gas-6 and MFG-E8, which then themselves bind to other receptors on the macrophage such as CD36 and Alpha-V Beta-3 Integrin.

2. In protists
In many protists, phagocytosis is used as a means of feeding, providing part or all of their nourishment. This is called phagotrophic nutrition, as distinguished from osmotrophic nutrition, which takes place by absorption.
• In some, such as amoeba, phagocytosis takes place by surrounding the target object with pseudopods, as in animal phagocytes. In humans, Entamoeba histolytica can phagocytose red blood cells.[3] This process is known as "erythrophagocystosis", and is considered the only reliable way to distinguish Entamoeba histolytica from noninvasive species such as Entamoeba dispar.[4]
• Ciliates also engage in phagocytosis.[5] In ciliates there is a specialized groove or chamber in the cell where phagocytosis takes place, called the cytostome or mouth.
The resulting phagosome may be merged with lysosomes containing digestive enzymes, forming a phagolysosome. The food particles will then be digested, and the released nutrients are diffused or transported into the cytosol for use in other metabolic processes.

Mixotrophy can involve phagotrophic nutrition and phototrophic nutrition.[6]

CELL (BIOLOGY)

often called the building bricks of life.[1] Some organisms, such as most bacteria, are unicellular (consist of a single cell). Other organisms, such as humans, are multicellular. (Humans have an estimated 100 trillion or 1014 cells; a typical cell size is 10 µm; a typical cell mass is 1 nanogram.) The largest known cell is an unfertilized ostrich egg cell.[2]

In 1835 before the final cell theory was developed, a Czech Jan Evangelista Purkyně observed small "granules" while looking at the plant tissue through a microscope. The cell theory, first developed in 1839 by Matthias Jakob Schleiden and Theodor Schwann, states that all organisms are composed of one or more cells. All cells come from preexisting cells. Vital functions of an organism occur within cells, and all cells contain the hereditary information necessary for regulating cell functions and for transmitting information to the next generation of cells.[3]
The word cell comes from the Latin cellula, meaning, a small room. The descriptive name for the smallest living biological structure was chosen by Robert Hooke in a book he published in 1665 when he compared the cork cells he saw through his microscope to the small rooms monks lived in.[4]

General Principles
Each cell is at least somewhat self-contained and self-maintaining: it can take in nutrients, convert these nutrients into energy, carry out specialized functions, and reproduce as necessary. Each cell stores its own set of instructions for carrying out each of these activities.

All cells have several different abilities:[5]
• Reproduction by cell division: (binary fission/mitosis or meiosis).
• Use of enzymes and other proteins coded for by DNA genes and made via messenger RNA intermediates and ribosomes.
• Metabolism, including taking in raw materials, building cell components, converting energy, molecules and releasing by-products. The functioning of a cell depends upon its ability to extract and use chemical energy stored in organic molecules. This energy is released and then used in metabolic pathways.
• Response to external and internal stimuli such as changes in temperature, pH or levels of nutrients.
• Cell contents are contained within a cell surface membrane that is made from a lipid bilayer with proteins embedded in it.
Some prokaryotic cells contain important internal membrane-bound compartments,[6] but eukaryotic cells have a specialized set of internal membrane compartments.

Anatomy of cells
There are two types of cells: eukaryotic and prokaryotic. Prokaryotic cells are usually independent, while eukaryotic cells are often found in multicellular organisms.

Prokaryotic cells
eukaryotes. There are two kinds of prokaryotes: bacteria and archaea; these share a similar overall structure.

A prokaryotic cell has three architectural regions:
• on the outside, flagella and pili project from the cell's surface. These are structures (not present in all prokaryotes) made of proteins that facilitate movement and communication between cells;
• enclosing the cell is the cell envelope - generally consisting of a cell wall covering a plasma membrane though some bacteria also have a further covering layer called a capsule. The envelope gives rigidity to the cell and separates the interior of the cell from its environment, serving as a protective filter. Though most prokaryotes have a cell wall, there are exceptions such as Mycoplasma (bacteria) and Thermoplasma (archaea)). The cell wall consists of peptidoglycan in bacteria, and acts as an additional barrier against exterior forces. It also prevents the cell from expanding and finally bursting (cytolysis) from osmotic pressure against a hypotonic environment. Some eukaryote cells (in plants and fungi) also have a cell wall;
• inside the cell is the cytoplasmic region that contains the cell genome (DNA) and ribosomes and various sorts of inclusions. A prokaryotic chromosome is usually a circular molecule (an exception is that of the bacterium Borrelia burgdorferi, which causes Lyme disease). Though not forming a nucleus, the DNA is condensed in a nucleoid. Prokaryotes can carry extrachromosomal DNA elements called plasmids, which are usually circular. Plasmids enable additional functions, such as antibiotic resistance.

Eukaryotic cells
Eukaryotic cells are about 10 times the size of a typical prokaryote and can be as much as 1000 times greater in volume. The major difference between prokaryotes and eukaryotes is that eukaryotic cells contain membrane-bound compartments in which specific metabolic activities take place. Most important among these is the presence of a cell nucleus, a membrane-delineated compartment that houses the eukaryotic cell's DNA. It is this nucleus that gives the eukaryote its name, which means "true nucleus." Other differences include:
• The plasma membrane resembles that of prokaryotes in function, with minor differences in the setup. Cell walls may or may not be present.
• The eukaryotic DNA is organized in one or more linear molecules, called chromosomes, which are associated with histone proteins. All chromosomal DNA is stored in the cell nucleus, separated from the cytoplasm by a membrane. Some eukaryotic organelles such as mitochondria also contain some DNA.
• Eukaryotes can move using cilia or flagella. The flagella are more complex than those of prokaryotes.

PHAGOCYTES

Phagocytes are the white blood cells that protect the body by ingesting (phagocytosing) harmful foreign particles, bacteria and dead or dying cells. They are essential for fighting infections, and for subsequent immunity.[1] Phagocytes are important throughout the animal kingdom,[2] and are highly developed in vertebrates.[3] One liter of human blood contains about six billion phagocytes.[4] Their name comes from the Greek phagein, 'to eat or devour', and kutos, 'hollow vessel'.[5] Phagocytes were first discovered in 1882 by Ilya Ilyich Mechnikov while he was studying starfish larvae.[6] Mechnikov was awarded the 1908 Nobel Prize in Physiology or Medicine for his discovery.[7] Phagocytes occur in many species; some amoebae behave like macrophages which suggests that phagocytes appeared early in the evolution of life.[8]

Phagocytes of humans and other animals are called professional or non-professional, depending on how effective they are at phagocytosis.[9] The professional phagocytes include cells called neutrophils, monocytes, macrophages, dendritic cells, and mast cells.[10] The main difference between professional and non-professional phagocytes is that the professional phagocytes have molecules called receptors on their surfaces that can detect harmful objects, such as bacteria, that are not normally found in the body.[11] Phagocytes are therefore crucial in fighting infections, as well as in maintaining healthy tissues by removing dead and dying cells that have reached the end of their life-span.[12]

During an infection, chemical signals attract phagocytes to places where the pathogen has invaded the body. These chemicals may come from bacteria, or from other phagocytes already present. The phagocytes move by a method called chemotaxis. When bacteria touch a phagocyte, they bind to the receptors on the phagocyte's surface and are consumed.[13] When a pathogen enters some phagocytes, this can trigger a chemical attack by the phagocytes that uses oxidants and nitric oxide to kill the pathogen.[14] After phagocytosis, macrophages and dendritic cells can also participate in antigen presentation: this is when the phagocyte moves parts of the ingested material back to its surface. This material is then displayed to other cells of the immune system. Some phagocytes then travel to the body's lymph nodes and display the material to white blood cells called lymphocytes. This process is important in building immunity.[15] However, many pathogens have evolved methods to counter attacks by phagocytes.[1]

History
The Russian zoologist Ilya Ilyich Mechnikov (1845–1916) first recognized that specialized cells were involved in defense against microbial infections. In 1882, he studied motile (freely moving) cells in the larvae of starfishes, believing they were important to the animals' immune defenses. To test his idea, he inserted small thorns from a tangerine tree into the larvae. After a few hours he noticed that the motile cells had surrounded the thorns.[16] Mechnikov traveled to Vienna and shared his ideas with Carl Friedrich Claus who suggested the name ‘‘phagocyte’’ (from the Greek words phagein, meaning 'to eat or devour', and kutos, meaning 'hollow vessel'[5]) for the cells that Mechnikov had observed.[17]
A year later, Mechnikov studied a fresh-water crustacean called Daphnia, a tiny transparent animal that can be examined directly under a microscope. He discovered that fungal spores that attacked the animal were destroyed by phagocytes. He went on to extend his observations to the white blood cells of mammals and discovered that the bacterium Bacillus anthracis could be engulfed and killed by phagocytes, a process that he called phagocytosis.[18] Mechnikov proposed that phagocytes were a primary defense against invading organisms.

In 1903, Amroth Wright discovered that phagocytosis was reinforced by specific antibodies which he called opsonins, from the Greek "opson", a dressing or relish.[19] Mechnikov was awarded (jointly with Paul Ehrlich) the 1908 Nobel Prize in Physiology or Medicine for his work on phagocytes and phagocytosis.[7]
Although the importance of these discoveries slowly gained acceptance during the early twentieth century, the intricate relationships between phagocytes and all the other components of the immune system were not known until the 1980s.[20]

Phagocytosis
Phagocytosis is the process of taking in particles such as bacteria, parasites, dead host cells and cellular and foreign debris by a cell.[21] It involves a chain of molecular processes.[22] Phagocytosis occurs after the foreign body, a bacterial cell for example, has bound to molecules called "receptors" that are on the surface of the phagocyte. Then the phagocyte stretches itself around the bacterium and engulfs it. Phagocytosis of bacteria by human neutrophils takes on average nine minutes.[23] Once inside this phagocyte, the bacterium is trapped in a compartment called a phagosome. Within one minute the phagosome merges with either a lysosome or a granule to form a phagolysosome. The imprisoned bacterium is then submitted to a formidable battery of killing mechanisms,[24] and is dead a few minutes later.[23] Dendritic cells and macrophages are not so fast and phagocytosis can take many hours in these cells. Macrophages are slow and untidy eaters but they engulf huge quantities of material and frequently release some undigested back into the tissues. This debris serves as a signal to recruit more phagocytes from the blood.[25] Phagocytes will eat almost anything; scientists have fed macrophages with iron filings and then used a small magnet to separate them from other cells in a mixture.[26]

A phagocyte has many types of receptors on its surface that are used to bind material.[1] They include opsonin receptors, scavenger receptors, and Toll-like receptors. Opsonin receptors increase the phagocytosis of bacteria that have been coated with complement or IgG antibodies. Complement is the name given to a complex series of protein molecules found in the blood that destroy or mark cells for destruction.[27] Scavenger receptors bind to a large range of molecules on the surface of bacterial cells, and Toll-like receptors—so called because of their similarity to well-studied receptors in fruit flies that are encoded by the Toll gene—bind to more specific molecules. Binding to Toll-like receptors increases phagocytosis and causes the phagocyte to release a group of hormones that cause inflammation.[1]

Methods of killing
The killing of microbes is a critical function of phagocytes,[28] and is either performed within the phagocyte (intracellular killing) or outside of the phagocyte (extracellular killing).

Oxygen-dependent intracellular killing
When a phagocyte ingests bacteria (or any material), its oxygen consumption increases. The increase in oxygen consumption is called a respiratory burst, which produces reactive oxygen-containing molecules that are anti-microbial.[29] The oxygen compounds are toxic to both the invader and the cell itself, so they are kept in compartments inside the cell. This method of killing invading microbes by using the reactive oxygen-containing molecules is referred to as oxygen-dependent intracellular killing, of which there are two types.[14]

The first type is the oxygen-dependent production of a superoxide,[1] which is an important, oxygen-rich, bacteria-killing substance.[30] The superoxide is converted to hydrogen peroxide and singlet oxygen by an enzyme called superoxide dismutase. Superoxides also react with the hydrogen peroxide to produce hydroxyl radicals which assist in killing the invading microbe.[1]
The second type involves the use of the enzyme myeloperoxidase from neutrophil granules.[31] When granules fuse with a phagosome, myeloperoxidase is released into the phagolysosome and this enzyme uses hydrogen peroxide and chlorine to create hypochlorite, a substance used in domestic bleach. Hypochlorite is extremely toxic to bacteria.[1] Myeloperoxidase contains a heme pigment, which makes secretions rich in neutrophils, such as pus and infected sputum, green.[32]

Oxygen-independent intracellular killing
Phagocytes can also kill microbes by oxygen-independent methods, but these are not as effective as the oxygen-dependent ones. There are four main types: The first uses electrically charged proteins which damage the bacterium's membrane. The second type uses lysozymes; these enzymes break down the bacterial cell wall. The third type uses lactoferrins which are present in neutrophil granules and remove essential iron from bacteria.[33] The fourth type uses proteases and hydrolytic enzymes; these enzymes are used to digest the proteins of destroyed bacteria.[34]
Gambar 4. Micrograph of Gram-stained pus showing Neisseria gonorrhoeae bacteria inside phagocytes and their relative sizes

Intracellular : In cell biology, molecular biology and related fields, the word intracellular means "inside the cell".
It is used in contrast to extracellular (outside the cell). The cell membrane (and, in plants, the cell wall) is the barrier between the two, and chemical composition of intra- and extracellular milieu can be radically different. In most organisms, for example, a Na+/K+ ATPase maintains a high potassium level inside cells while keeping sodium low, leading to chemical excitability.

Extracellular killing
Interferon-gamma—which was once called macrophage activating factor—stimulates macrophages to produce nitric oxide. The source of interferon-gamma can be CD4+ T cells, CD8+ T cells, Natural Killer cells, B cells, Natural Killer T cells, monocytes, macrophages, or dendritic cells.[35] Nitric oxide is then released from the macrophage and, because of its toxicity, kills microbes near the macrophage.[1] Activated macrophages produce and secrete tumor necrosis factor. This cytokine—a class of signaling molecules[36]—kills cancer cells and cells infected by viruses, and helps to activate the other cells of the immune system.[37]
In some diseases, e.g. the rare chronic granulomatous disease, the efficiency of phagocytes is impaired and recurrent bacterial infections are a problem.[38] In this disease there is an abnormality affecting different elements of oxygen-dependent killing. Other rare congenital abnormalities, such as Chediak-Higashi Syndrome, are also associated with defective killing of ingested microbes.[39]

Extracellular : In cell biology, molecular biology and related fields, the word extracellular (or sometimes extracellular space) means "outside the cell". This space is usually taken to be outside the plasma membranes, and occupied by fluid. The term is used in contrast to intracellular (inside the cell).
The composition of the extracellular space includes metabolites, ions, proteins, and many other substances that might affect cellular function. For example, hormones act by travelling the extracellular space towards biochemical receptors on cells. Other proteins that are active outside the cell are the digestive enzymes.
The term 'extracellular' is often used in reference to the extracellular fluid (ECF) which composes about 15 litres of the average human body. The cell membrane (and, in plants and fungi, the cell wall) is the barrier between the two, and chemical composition of intra- and extracellular milieu can be radically different. In most organisms, for example, a Na+/K+-ATPase pump maintains a high concentration of sodium ions outside cells while keeping that of potassium low, leading to chemical excitability. Many cold-tolerant plants force water into the extracellular space when the temperature drops below 0 degrees Celsius, so that when it freezes, it does not lyse the plants' cells. [1]

Two compartments comprise the extracellular space: the vascular space and the interstitial space.[2]

Viruses
Viruses can only reproduce inside cells and they gain entry by using many of the receptors involved in immunity. Once inside the cell, viruses use the cell's biological machinery to their own advantage—forcing the cell to make hundreds of identical copies of themselves. Although phagocytes and other components of the innate immune system can, to a limited extent, control viruses, once they are inside cells the adaptive immune responses, particularly the lymphocytes, are more important for defense.[40] At the sites of viral infections, lymphocytes often vastly outnumber all the other cells of the immune system; this is common in viral meningitis.[41] Virus infected cells that have been killed by lymphocytes are cleared from the body by phagocytes.[42]

Role in apoptosis
Animals' cells constantly die and are replaced by cell division. In adults, the number of cells is kept relatively constant. Cells are usually replaced when they malfunction or become diseased, but cell proliferation must be offset by cell death.[12] There are two different ways a cell can die: by necrosis or by apoptosis. In contrast to necrosis, which often results from disease or trauma, apoptosis—or programmed cell death—is a normal healthy function of cells. The body has to rid itself of millions of dead or dying cells every day and phagocytes play a crucial role in this process.[43]

Dying cells that undergo the final stages of apoptosis[44] display molecules, such as phosphatidylserine, on their cell surface to attract phagocytes.[45] Phosphatidylserine is normally found on the cytosolic surface of the plasma membrane, but is redistributed during apoptosis to the extracellular surface by a hypothetical protein known as scramblase.[46] These molecules mark the cell for phagocytosis by cells that possess the appropriate receptors, such as macrophages.[47] The removal of dying cells by phagocytes occurs in an orderly manner without eliciting an inflammatory response and is an important function of phagocytes.[48]
Gambar 5. Apoptosis—phagocytes clear fragments of dead cells from the body

Interactions with other cells
Phagocytes are not bound to any particular organ but move through the body, interacting with the other phagocytic and non-phagocytic cells of the immune system. They can communicate with other cells by producing chemicals called cytokines, which recruit other phagocytes to the site of infections or stimulate dormant lymphocytes.[49] Phagocytes form part of the innate immune system which animals, including humans, are born with. Innate immunity is very effective but non-specific in that it does not discriminate between different sorts of invaders. On the other hand, the adaptive immune system of jawed vertebrates—the basis of acquired immunity—is highly specialized and can protect against almost any type of invader.[50] The adaptive immune system is dependent on lymphocytes, which are not phagocytes, but produce protective proteins called antibodies which tag invaders for destruction and prevent viruses from infecting cells.[51] Phagocytes, in particular dendritic cells and macrophages, stimulate lymphocytes to produce antibodies by an important process called antigen presentation.[52]

Antigen presentation
Antigen presentation is a process in which some phagocytes move parts of engulfed materials back to the surface of their cells and "present" them to other cells of the immune system.[53] There are two "professional" antigen-presenting cells: macrophages and dendritic cells.[54] After engulfment, foreign proteins (the antigens) are broken down into peptides inside dendritic cells and macrophages. These peptides are then bound to the cell's major histocompatibility complex (MHC) glycoproteins, which carry the peptides back to the phagocytes surface where they can be "presented" to lymphocytes.[15] Mature macrophages do not travel far from the site of infection, but dendritic cells can reach the body's lymph nodes where there are millions of lymphocytes.[55] This enhances immunity because the lymphocytes respond to the antigens presented by the dendritic cells just as they would at the site of the original infection.[56] But dendritic cells do not always co-operate with lymphocytes and will destroy them if necessary to protect the body. This is seen in a process called tolerance.[57]

Immunological tolerance
Dendritic cells also promote immunological tolerance,[58] which stops the body attacking itself. The first type of tolerance is central tolerance: when T cells first depart from the thymus, dendritic cells destroy the T cells that carry antigens that would cause the immune system to attack itself. The second type of immunological tolerance is peripheral tolerance. Some T cells that possess antigens that would cause them to attack "self" slip through the first process of tolerance, some T cells develop self-attacking antigens later in life, and some self-attacking antigens are not found in the thymus; because of this dendritic cells will work, again, to restrain the activities of self-attacking T cells outside of the thymus. Dendritic cells can do this by destroying them or by recruiting the help of regulatory T cells to inactivate the harmful T cells' activities.[59] When immunological tolerance fails, autoimmune diseases can follow.[60] On the other hand, too much tolerance allows some infections, like HIV, to go unnoticed.[59]

Professional phagocytes
Phagocytes of humans and other jawed vertebrates are divided into "professional" and "non-professional" groups based on the efficiency with which they participate in phagocytosis.[9] The professional phagocytes are the monocytes, macrophages, neutrophils, tissue dendritic cells and mast cells.[10] One liter of human blood contains about six billion phagocytes.[4]
Gambar 7. Phagocytes derive from stem cells in the bone marrow

Activation
All phagocytes, and especially macrophages, exist in degrees of readiness. Macrophages are usually relatively dormant in the tissues and proliferate slowly. In this semi-resting state they clear away dead host cells and other non-infectious debris and rarely take part in antigen presentation. But during an infection they receive chemical signals—usually interferon gamma—which increases their production of MHC II molecules and which prepares them for presenting antigens. In this state, macrophages are good antigen presenters and killers. However, if they receive a signal directly from an invader they become "hyperactivated", stop proliferating and concentrate on killing. Their size and rate of phagocytosis increases—some become large enough to engulf invading protozoa.[61]
In the blood, neutrophils are inactive but are swept along at high speed. When they receive signals from macrophages at the sites of inflammation, they slow down and leave the blood. In the tissues they are activated by cytokines and arrive at the battle scene ready to kill.[62]

Migration
When an infection occurs, a chemical "SOS" signal is given off to attract phagocytes to the site.[63] These chemical signals may include proteins from invading bacteria, clotting system peptides, complement products, and cytokines that have been given off by macrophages located in the tissue near the infection site.[1] Another group of chemical attractants are cytokines which recruit neutrophils and monocytes from the blood.[13]

To reach the site of infection, phagocytes leave the blood stream and enter the affected tissues. Signals from the infection cause the endothelial cells that line the blood vessels to make a protein called selectin which neutrophils stick to on passing by. Other signals called vasodilators loosen the junctions connecting endothelial cells, allowing the phagocytes to pass through the wall. Chemotaxis is the process by which phagocytes follow the cytokine "scent" to the infected spot.[1] Neutrophils travel across epithelial cell-lined organs to sites of infection and although this is an important component of fighting infection, the migration itself can result in disease-like symptoms.[64] During an infection millions of neutrophils are recruited from the blood but they die after a few days.[65]

Monocytes
Monocytes develop in the bone marrow and reach maturity in the blood. Mature monocytes have large, smooth, lobed nuclei and abundant cytoplasm that contains granules. Monocytes ingest foreign or dangerous substances and present antigens to other cells of the immune system. Monocytes form two groups: a circulating group and a marginal group which remain in other tissues (approximately 70% are in the marginal group). Most monocytes leave the blood stream after 20–40 hours to travel to tissues and organs, and in doing so transform into macrophages[66] or dendritic cells depending on the signals they receive.[67] There are about 500 million monocytes in one liter of human blood.[4]

magnification
Macrophages
Mature macrophages do not travel far but stand guard over those areas of the body that are exposed to the outside world. There they act as garbage collectors, antigen presenting cells, or ferocious killers depending on the signals they receive.[68] They derive from monocytes, granulocyte stem cells, or the cell division of pre-existing macrophages.[69] Human macrophages are about 21 micrometers in diameter.[70]
This type of phagocyte does not have granules but contains many lysosomes. Macrophages are found throughout the body in almost all tissues and organs (e.g., microglial cells in the brain and alveolar macrophages in the lungs) where they silently lie in wait. A macrophage's location can determine its size and appearance. Macrophages cause inflammation through the production of interleukin-1, interleukin-6, and TNF-alpha.[71] Macrophages are usually only found in tissue and are rarely seen in blood circulation. The life-span of tissue macrophages has been estimated to range from four to fifteen days.[72]

Macrophages can be activated to perform functions that a resting monocyte cannot.[71] T helper cells (also known as effector T cells or Th cells), a sub-group of lymphocytes, are responsible for the activation of macrophages. Th1 cells activate macrophages by signaling with IFN-gamma and displaying the protein CD40 ligand.[73] Other signals include TNF-alpha and lipopolysaccharides from bacteria.[71] Th1 cells can recruit other phagocytes to the site of the infection in several ways. They secrete cytokines that act on the bone marrow to stimulate the production of monocytes and neutrophils and they secrete some of the cytokines and that are responsible for the migration of monocytes and neutrophils out of the blood stream.[74] Th1 cells come from the differentiation of CD4 T cells once they have responded to antigen in the secondary lymphoid tissues.[71] Activated macrophages play a potent role in tumor destruction by producing TNF-alpha, IFN-gamma, nitric oxide, reactive oxygen compounds, cationic proteins, and hydrolytic enzymes.[71]
Gambar 10. Pus oozing from an abscess caused by bacteria—pus contains millions of phagocytes

Neutrophils
Neutrophils are normally found in the bloodstream and are the most abundant type of phagocyte, constituting 50% to 60% of the total circulating white blood cells.[75] One liter of human blood contains about five billion neutrophils,[4] which are about 10 micrometers in diameter,[76] and live for only about five days.[37] Once they have received the appropriate signals, it takes them about thirty minutes to leave the blood and reach the site of an infection.[77] They are ferocious eaters and rapidly engulf invaders coated with antibodies and complement, and damaged cells or cellular debris. Neutrophils do not return to the blood; they turn into pus cells and die.[77] Mature neutrophils are smaller than monocytes, and have a segmented nucleus with several sections; each section is connected by chromatin filaments—neutrophils can have 2–5 segments. Neutrophils do not normally exit the bone marrow until maturity but during an infection neutrophil precursors called myelocytes and promyelocytes are released.[78]

The intra-cellular granules of the human neutrophil have long been recognized for their protein-destroying and bactericidal properties.[79] Neutrophils can secrete products that stimulate monocytes and macrophages. Neutrophil secretions increase phagocytosis and the formation of reactive oxygen compounds involved in intracellular killing.[80] Secretions from the primary granules of neutrophils stimulate the phagocytosis of IgG antibody-coated bacteria.[81]
Gambar 11. A neutrophil with a segmented nucleus (center and surrounded by erythrocytes), the intra-cellular granules are visible in the cytoplasm (Giemsa stained high magnification)

Dendritic cells
Dendritic cells are specialized antigen-presenting cells that have long outgrowths called dendrites,[82] which help to engulf microbes and other invaders.[83][84] Dendritic cells are present in the tissues that are in contact with the external environment; mainly the skin, the inner lining of the nose, lungs, stomach and intestines.[85] Once activated, they mature and migrate to the lymphoid tissues where they interact with T cells and B cells to initiate and orchestrate the adaptive immune response.[86] Mature dendritic cells activate T helper cells and cytotoxic T cells.[87] The activated helper T cells interact with macrophages and B cells to activate them in turn. In addition, dendritic cells can influence the type of immune response produced; when they travel to the lymphoid areas where T cells are held they can activate T cells which then differentiate into killer T cells or helper T cells.[88]

Mast cells
Mast cells have Toll-like receptors and interact with dendritic cells, B cells, and T cells, to help mediate adaptive immune functions. Mast cells express MHC class II molecules and can participate in antigen presentation; however, the mast cell's role in antigen presentation is not very well understood.[89] Mast cells can consume and kill gram-negative bacteria (e.g., salmonella), and process their antigens.[90] They specialize in processing the fimbrial proteins on the surface of bacteria, which are involved in adhesion to tissues.[91][92] In addition to these functions, mast cells produce cytokines that induce an inflammatory response.[93] This is a vital part of the destruction of microbes because they attract more phagocytes to the site of infection.[90]

Non-professional phagocytes
Dying cells and foreign organisms are consumed by cells other than the "professional" phagocytes.[95] These cells include epithelial cells, endothelial cells, fibroblasts, and mesenchymal cells. They are called non-professional phagocytes, to emphasize that, in contrast to professional phagocytes, phagocytosis is not their principal function.[96] Fibroblasts, for example, only make ineffective attempts to ingest foreign particles.[97]

Non-professional phagocytes are more limited limited than professional phagocytes in the type of particles they can take up. This is due to their lack of efficient phagocytic receptors, particularly opsonins—which are antibodies and complement attached to invaders by the immune system.[11] Additionally, most nonprofessional phagocytes do not produce reactive oxygen-containing molecules in response to phagocytosis.[98]

Pathogen evasion and resistance
A pathogen is only successful in infecting an organism if it can get past its defenses. Pathogenic bacteria and protozoa have developed a variety of methods to resist attacks by phagocytes and many actually survive and replicate within phagocytic cells.[99][100]

Avoiding contact
There are several ways bacteria avoid contact with phagocytes. First, they can grow in sites that phagocytes are not capable of traveling to (e.g., the surface of unbroken skin). Second, bacteria can suppress the inflammatory response; without this response to infection phagocytes cannot respond adequately. Third, some species of bacteria can inhibit the ability of phagocytes to travel to the site of infection by interfering with chemotaxis.[99] Fourth, some bacteria can avoid contact with phagocytes by tricking the immune system into "thinking" that the bacteria are "self". Treponema pallidum—the bacterium that causes syphilis—hides from phagocytes by coating its surface with fibronectin,[101] which is produced naturally by the body and plays a crucial role in wound healing.[102]

Avoiding engulfment
Bacteria often produce proteins or sugars that coat their cells and interfere with phagocytosis; these are called capsules.[99] An example is the K5 capsule and O75 O antigen found on the surface of Escherichia coli,[103] and the exopolysaccharide capsules of Staphylococcus epidermidis.[104] Streptococcus pneumoniae produces several types of capsule which provide different levels of protection,[105] and group A streptococci produce proteins such as M protein and fimbrial proteins to block engulfment. Some proteins hinder opsonin-related ingestion; Staphylococcus aureus produces Protein A to block antibody receptors which decreases the effectiveness of opsonins.[106]

Survival inside the phagocyte
Bacteria have developed ways to survive inside phagocytes, where they continue to evade the immune system.[107] To get safely inside the phagocyte they express proteins called "invasins". When inside the cell they remain in the cytoplasm and avoid toxic chemicals contained in the phagolysosomes.[108] Some bacteria prevent the fusion of a phagosome and lysosome, to form the phagolysosome.[99] Other pathogens, such as Leishmania, create a highly-modified vacuole inside the phagocyte, which helps them persist and replicate.[109] Legionella pneumophila produces secretions which cause the phagosome to fuse with vesicles other than the ones that contain toxic substances.[110] Other bacteria are capable of living inside of the phagolysosome. Staphylococcus aureus, for example, produces the enzymes catalase and superoxide dismutase which break down chemicals—such as hydrogen peroxide—produced by phagocytes to kill bacteria.[111] Bacteria may escape from the phagosome before the formation of the phagolysosome: Listeria monocytogenes can make a hole in the phagosome wall using a enzymes called listeriolysin O and phospholipase C.[112]

Killing
Bacteria have developed several ways of killing phagocytes.[106] These include: cytolysins which form pores in the phagocyte's cell membranes; streptolysins and leukocidins which cause neutrophils' granules to rupture and release toxic substances,[113][114] and exotoxins which reduce the supply of a phagocyte's ATP, needed for phagocytosis. After a bacterium is ingested it may kill the phagocyte by releasing toxins that travel through the phagosome or phagolysosome membrane to target other parts of the cell.[99]

Disruption of cell signaling
Some survival strategies often involve disrupting cytokines and other methods of cell signaling to prevent the phagocyte's responding to invasion.[115] The protozoan parasites Toxoplasma gondii, Trypanosoma cruzi and Leishmania infect macrophages and each has unique ways of taming them. Some species of Leishmania alter the infected macrophage's signalling and repress the production of cytokines and microbicidal molecules—nitric oxide and reactive oxygen species—and compromise antigen presentation.[116]

Host damage by phagocytes
Macrophages and neutrophils, in particular, play a central role in the inflammatory process, by releasing proteins and small-molecule inflammatory mediators that both control infection and can damage host tissue. In general phagocytes aim to destroy pathogens by engulfing them and subjecting them to battery of toxic chemicals inside a phagolysosome. If a phagocyte fails to engulf it's target, these toxic agents can be released into the environment (an action referred to as "frustrated phagocytosis"). As these agents are also toxic to host cells they can cause extensive damage to healthy cells and tissues.[97]
When neutrophils release their granule contents in the kidney, the contents of the granule (reactive oxygen compounds and proteases) degrade the extracellular matrix of host cells and can cause damage to glomerular cells, affecting their ability to filter blood and causing changes in shape. In addition, phospholipase products (e.g., leukotrienes) intensify the damage. This release of substances promotes chemotaxis of more neutrophils to the site of infection and glomerular cells can be damaged further by the adhesion molecules during the migration of neutrophils. The injury done to the glomerular cells can cause renal failure.[117]
Neutrophils also play a key role in the development of most forms of acute lung injury (ALI).[118] In ALI, activated neutrophils release the contents of their toxic granules into the lung environment.[119] Experiments have shown that a reduction in the number of neutrophils lessens the effects of ALI,[120] but treatment by inhibiting neutrophils is not clinically realistic, as it would leave the host vulnerable to infection.[119] Damage by neutrophils can contribute to liver dysfunction and injury in response to the release of endotoxins produced by bacteria, sepsis, trauma, alcoholic hepatitis, ischemia, and hypovolemic shock resulting from acute hemorrhage.[121]
Chemicals released by macrophages can also damage host tissue. TNF-α is an important chemical that is released by macrophages that causes the blood in small vessels to clot to prevent an infection from spreading.[122] However, if a bacterial infection spreads to the blood, TNF-α is released into vital organs which can cause vasodilation and a decrease in plasma volume; these in turn can be followed by septic shock. During septic shock, TNF-α release causes a blockage of the small vessels that supply blood to the vital organs, and the organs may fail. Septic shock can lead to death.[13]

Evolutionary origins
Phagocytosis is common and probably appeared early in evolution,[123] evolving first in unicellular eukaryotes.[124] Amoebae, are unicellular protists that separated from the tree leading to metazoa shortly after the divergence of plants, but they share many specific functions with mammalian phagocytic cells. [124] Dictyostelium discoideum, for example, is an amoeba that lives in the soil and feeds on bacteria. Like animal phagocytes, it engulfs bacteria by phagocytosis mainly through Toll-like receptors and has other biological functions in common with macrophages.[125] Dictyostelium discoideum is social and aggregates when starved to form a migrating slug. This multicellular organism eventually produces a fruiting body with spores that are resistant to environmental dangers. Before the formation of fruiting bodies, the cells can migrate as slug-like organisms for several days. During this time, exposure to toxins or bacterial pathogens have the potential to compromise survival of the amoebae by limiting spore production. Some of the amoebae engulf bacteria and absorb toxins while circulating within the slug and these amoebae eventually die. They are genetically identical to the other amoebae in the slug and their sacrificing themselves to protect the other amoebae from bacteria is similar to the self-sacrifice by the phagocytes seen in the immune system of higher organisms. This innate immune function in social amoebae suggests an ancient cellular foraging mechanism that may have been adapted to defense functions well before the diversification of the animals.[126] But a common ancestry with mammalian phagocytes has not been proven. Phagocytes occur throughout the animal kingdom,[2] from marine sponges to insects and lower and higher vertebrates.[127][128] The ability of amoebae to distinguish between self and non-self is a pivotal one which is the root of the immune system of many species.[8]

NB. From Any Soerce Refference

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MARGA SARGASSUM DI PERAIRAN INDONESIA

Algae Sargassum merupakan salah satu marga Sargassum termasuk dalam kelas Phaeophyceae. Ada 150 jenis Marga Sargassum yang dijumpai di daerah perairan tropis, subtropis dan daerah bermusim dingin (NIZAMUDDIN 1970). Habitat algae Sargassum tumbuh diperairan pada kedalaman 0,5 – 10 m ada arus dan ombak. Pertumbuhan algae ini sebagai makro algae bentik melekat pada substrat dasar perairan. Di daerah tubir tumbuh membentuk rumpun besar, panjang thalli utama mencapai 0,5-3 m dengan untaian cabang thalli terdapat kantong udara (bladder), selalu muncul di permukaan air.

Di perairan Indonesia diperkirakan terdapat lebih dari 15 jenis algae Sargassum dan yang telah dikenal mencapai 12 jenis. Sedangkan di perairan Indo-Pasifik tercatat 58 jenis ( BOSSE 1928). Kehadiran marga Sargassum di berbagai daerah di Indonesia mempunyai sebutan nama yang berbeda-beda. Di kepulauan Seribu disebut oseng dan di Banten dinamakan kembang karang. Algae Sargassum tumbuh sepanjang tahun, tumbuhan ini bersifat “perenial” atau setiap musim barat maupun timur dapat dijumpai di berbagai perairan.

Algae Sargassum secara ekologis ikut andil dalam pembentukan ekosistem terumbu karang dan merupakan tempat asuhan bagi biota kecil, termasuk untuk perlindungan benih ikan dan benur udang serta sarang melekatnya telur cumi-cumi. Jenis Sargassum yang telah dipasarkan di daerah Jawa Barat dari jenis Sargassum polycystum, Sargassum binderi dan Sargassum duplicatum. Marga Sargassum mengandung bahan alginat dan iodin, bermanfaat sebagai bahan industri makanan, farmasi, kosmetik dan tekstil.

HABITAT DAN SEBARAN

Lingkungan tempat tumbuh algae Sargassum terutama di daerah perairan yang jernih yang mempunyai substrat dasar batu karang, karang mati, batuan vulkanik dan benda-benda yang bersifat massive yang berada di dasar perairan. Algae Sargassum tumbuh dari daerah intertidal, subtidal sampai daerah tubir dengan ombak besar dan arus deras. Kedalaman untuk pertumbuhan dari 0,5 – 10 m. Marga Sargassum termasuk dalam kelas Phaeophyceae tumbuh subur pada daerah tropis, suhu perairan 27,25 – 29,30 oC dan salinitas 32–33,5 %o. Kebutuhan intensitas cahaya matahari marga Sargassum lebih tinggi dari pada marga algae merah. BONEY (1965) menyatakan pertumbuha Sargassum mebutuhkan intensitas cahaya matahari berkisar 6500 – 7500 lux. Algae Sargassum tumbuh berumpun dengan untaian cabang-cabang. Panjang thalli utama mencapai 1 – 3 m dan tiap-tiap percabangan terdapat gelembung udara berbentuk bulat yang disebut “Bladder,” berguna untuk menopang cabang-cabang thalli terapung ke arah permukaan air untuk mendapatkan intensitas cahaya matahari,

1. Sebaran lokal.
Kehadiran algae Sargassum tumbuh di bentangan perairan pantai di zona paparan terumbu (reef flats) mulai dari garis pantai sampai ujung tubir termasuk dalam perairan intertidal dan subtidal (Gambar 1.) antara lain :

a). Daerah pantai (beach/tide pool area)
Daerah Pantai merupakan zona yang dimanfaatkan untuk tempat kegiatan rekreasi kadang-kadang mempunyai substrat bervariasi pada umumnya berpasir, namun apabila substrat terbentuk dari campuran batu karang akan tumbuh berbagai jenis makro algae. Pada saat surut rendah yang lama akan mengalami kekeringan. Di Pantai bersubstrat pasir pada umumnya sedikit dijumpai pertumbuhan marga Sargassum, sedangkan di pantai bersubstrat batu karang merupakan habitat algae Sargassum yang ideal. Di beberapa pantai dapat dijumpai termasuk pantai selatan Pulau Jawa, Selat Sunda, sebagian pulau di perairan Batam dan Bangka-Belitung. Algae Sargassum yang tumbuh banyak diperoleh dari jenis Sargassum polycystum.

b). Paparan Terumbu (reef flats).
Daerah paparan terumbu merupakan bagian habitat algae Sargassum. Di perairan Indonesia paparan terumbu ada yang berpunggung terumbu dan tidak berpunggung terumbu didaerah perairan tubir langsung dalam (drop off). Di substrat paparan yang berbatu karang merupakan tempat untuk melekatkan thalli selama pertumbuhan berlangsung dan sebagai tempat melekat perkecambahan spora. Paparan terumbu yang berasal dari batuan vulkanik dan batu karang boulder sering dijumpai lekukan dan parit (moat) daerah ini berombak besar dan arus deras. Pertumbuhan Sargassum kebanyakan dari jenis Sargassum binderi dan Sargassum duplicatum, biasanya kerangka thalli sangat kuat, thalli utama berbentuk gepeng, permukaan halus dan licin. Secara umum bahwa pertumbuhan algae Sargassum yang dominan didaerah paparan terumbu adalah jenis Sargassum polycystum, Sargassum echinocarpum dan Sargassum crassifolium.

c). Punggung terumbu (ridge)
Di perairan pantai di Indonesia punggung terumbu kadang-kadang ada yang berpunggung terumbu dan tidak berpunggung terumbu. Punggung terumbu ini terbentuk dari algae kalkareous dari marga Porolithon atau terbentuk dari bongkahan karang yang telah mati. Daerah sekitar dinding punggung terumbu ini merupakan tempat tumbuh algae Sargassum, banyak dijumpai dari jenis Sargassum polycystum dan Sargassum echinocarpum. Pada waktu surut rendah rumpunan Sargassum mengalami perebahan dan saling bertumpang tindih dengan rumput laut jenis lainnya.

d). Tubir (reef slope)
Daerah tubir merupakan tempat tumbuh algae Sargassum dari jenis yang berthalli panjang 1 – 3 m. Pertumbuhan berasosiasi dengan karang hidup dan bonggol thalli (holdfast) menempel pada bagian karang yang telah mati dan lapuk. Pola pertumbuhan algae Sargassum di daerah tubir thalli dalam rumpun yang besar secara “Heliocentris” tertuju ke arah permukaan untuk mendapatkan sinar matahari yang lebih banyak. Pada waktu air surut keberadaan Sargassum di daerah tubir dapat diketahui dengan melihat gerombolan cabang thalli yang terapung di atas permukaan air. Kemampuan daya apung ini didukung oleh kantong gelembung udara yang terletak diketiak percabangan thalli utama. Pada umumnya algae Sargassum tumbuh di daerah tubir mempunyai karakteristik thalli utama sangat kuat, bentuk pipih dan daun licin halus berlendir. Jenis yang tumbuh di daerah tubir meliputi Sargassum binderi, Sargassum cinereum, Sargassum plagyophyllum dan Sargassum crassifolium.

e). Goba (lagoon)
Daerah goba merupakan tempat hidup dari semua jenis makro algae yang kebanyakan tumbuh di bibir goba terutama karang mati yang telah lapuk. Makro algae banyak yang berasosiasi dengan karang hidup, lamun dan biota lainnya. Perairan goba juga merupakan daerah interaksi dalam siklus rantai antar flora dan fauna yang hidup bersama baik sebagai “produkser” maupun “predator”. Marga Sargassum termasuk rumpun yang paling besar diantara marga rumput laut, sehingga keberadaan dalam perairan goba merupakan tempat asuhan dan berlindung biota kecil, karena arus dan ombak relatip tenang. Di daerah goba pertumbuhan makro algae reproduksinya melalui spora. Algae Sargassum yang tumbuh dominan diperairan ini meliputi Sargassum polycystum, Sargassum echinocarpum, Sargassum molleri dan Sargassum gracilimum.

2. Sebaran wilayah
Hasil penelitian makro algae di Indonesia menunjukan sebaran yang luas dan bervariasi. Algae Sargassum termasuk tumbuhan yang dominan dan distribusinya ada di seluruh perairan Indonesia.

a). Perairan Indonesia Bagian Barat.
Di perairan Indonesia Bagian Barat berdasarkan hasil penelitian yang telah dilakukan diperoleh 3 – 7 jenis Sargassum. Di perairan Laut Jawa yang berada di kepulauan Seribu ada 6 jenis (ATMADJA dan SULISTIJO 1980). Di Selat Sunda dan Teluk Lampung diperoleh 7 jenis. Di kepulauan Anambas, Natuna dan Batam ada 4 jenis. Kehadiran ini juga diperoleh dari perairan Selatan pulau Jawa di Binuangeun, Pameungpeuk, Pangandaran 6 jenis di perairan pantai Wonosari Krakal terdapat 3 jneis (KADI dan ATMADJA 1988). Algae Sargassum juga diperoleh dari Teluk Klabat, kepulauan Bangka, Belitung dan Karimata 2 jenis (KADI 2005). Di daerah perairan laut China Selatan di Singapura ada 7 jenis (WEI & CHIN 1983). Di Sabah Malaysia tercatat 8 jenis (Ismail 1981). Keberadaan makro algae Sargassum yang berada di negara tetangga dan di Indonesia Bagian Barat dan sekitarnya ada kesamaan jenis dengan populasi jenis tidak jauh berbeda.

b). Perairan Indonesia bagian Tengah.
Perairan pantai di beberapa pulau di Indonesia bagian tengah mempunyai paparan terumbu pendek dan terjal (drop off), kondisi ombak besar dan arus deras. Kehadiran algae Sargassum yang diperoleh berkisar 2 – 4 jenis, terdapat di paparan terumbu di Tanjung Benoa Bali 4 jenis dan di perairan pulau-pulau Sulawesi Selatan dan Tenggara 3 jenis (ATMADJA dan SULISTIJO 1980). Di perairan Pulau Lombok diperoleh 2 jenis. Sebaran algae terdapat di perairan sebelah utara di wilayah Indonesia bagian tengah meliputi Teluk Kwandang, Manado, pulau Ruang, Tagulandang, Pasige dan pulau Sangir Talaud terdapat 2 jenis. Di perairan Philippina merupakan daerah terdekat perairan Sulawesi Utara terdapat 5 jenis (TRONO & GANZON 1988).

c). Perairan Indonesia Bagian Timur.
Kondisi umum paparan terumbu di pulau-pulau Indonesia bagian Timur berbeda dengan Bagian Barat dan Tengah. Perbedaan substrat dan kondisi lingkungandi Indonesia Bagian Timur lebih banyak dipengaruhi oleh perairan Samudera Pasifik. Algae Sargassum yang tumbuh sebagian jenisnya berasal dari Samudera Pasifik. Di perairan Maluku terdapat 4 jenis Sargassum yang berbeda dengan jenis yang berada di perairan Samudera Hindia maupun laut China Selatan. ATMADJA dan SULISTIJO (1980) memperoleh 4 jenis Sargassum di pulau-pulau Kai Besar dan Seram. Keberadaan jenis ini terdapat pula di Kepulauan Maisel, pulau-pulau Penyu. Sebaran algae Sargassum di jumpai 2 jenis di perairan pulau Ternate, Bacan dan sekitarnya. Di pulau-pulau yang terletak di lautan Pasifik di Pulau-pulau Hawaii terdapat 3 jenis (MAGRUDER & HUNT 1979). Sebaran algae Sargassum tersebut sebagian jenisnya berada di perairan Indonesia.

REPRODUKSI MARGA SARGASSUM

Perkembangbiakan atau reproduksi marga Sargassum yang termasuk bangsa Fucales, marga Sargassaceae dikenal dua cara yaitu; Reproduksi asexual (vegetatif) dan sexual (generatif). Reproduksi vegetatif dilakukan melalui fragmentasi yaitu potongan thallus berkembang melakukan pertumbuhannya. Cara ini banyak dilakukan untuk usaha budidaya. Reproduksi generatif yaitu perkembangan individu melalui organ jantan (antheridia) dan organ betina (oogenia). Organ-organ tersebut terjadi dan berada dalam satu lobang yang disebut koseptakel. Antheridia maupun oogonia berada di atas sel tangkai yang tertanam pada dasar konseptakel. Dinding antheridia terdiri dua lapis di sebelah luar (exochite) dan sebelah dalam (endochite). Dinding oogonium terdiri tiga lapis di sebelah luar (exochite), bagian tengah (mesochite) dan bagian dalam (endochite). Secara umum reproduksi seksual makro algae coklat termasuk marga Sargassum ada beberapa tipe daur hidup antara lain :

1). Haplobiontik diploid yakni individu melakukan daur hidup secara diploid. Meiosis terjadi pada gamet (gametik meiosis) berkembang menjadi individu dewasa tipe daur hidup semacam ini banyak terdapat pada makro algae coklat dan hijau.

2). Diplobiontik yaitu dalam proses pembiakan terdapat dua individu dalam daur hidup gametophyte (gametofit) haploid yang menghasilkan gamet, dan sporophyte (sporofit) diploid yang menghasilkan spora. Tipe daur hidup ini lebih umum terdapat pada makro algae coklat, merah dan hijau. Pertemuan antara dua gamet jantan dan betina akan membentuk zigot yang kemudian berkembang menjadi sporofit. Individu baru inilah yang mengeluarkan spora dan berkembang melalui meiosis dan sporagenesis menjadi gametofit.

KANDUNGAN BAHAN KIMIA

Algae Sargassum mudah diperoleh di perairan Indonesia, kandungan bahan kimia utama sebagai sumber alginat dan mengandung protein, vitamin C, tannin, iodine, phenol sebagai obat gondok, anti bakteri dan tumor (TRONO & GANZON 1988), sebagai berikut :

1. Algin
Algin merupakan asam alginik, Alginik dalam bentuk derivat garam dinamakan garam alginat terdiri dari sodium alginat, potasium alginat dan amonium alginat. Garam alginat tidak larut dalam air, tetapi larut dalam larutan alkali. Asam alginik tersusun dari asam D-Manuronik dan asam L – Guluronik (Gambar 5.).

2. Manfaat alginat.
Kandungan koloid alginat dari algae Sargassum (Gambar 6.) dalam industri kosmetik digunakan sebagai bahan pembuat sabun, pomade, cream bodylotion, sampo dan cat rambut. Di industri farmasi sebagai bahan pembuat kapsul obat, tablet, salep, emulsifier, suspensi dan stabilizer. Di bidang pertanian sebagai bahan campuran insektisida dan pelindung kayu. Di industri makanan sebagai bahan pembuat saus dan campuran mentega. Manfaat lainnya dalam industri fotografi, kertas, tekstil dan keramik. Di bidang kesehatan iodine digunakan sebagai obat pencegah penyakit gondok.

PENUTUP

Di Indonesia sebaran makro algae Sargassum berada di pulau besar maupun kecil, dan jumlah jenisnya ada 12. Tumbuh di lingkungan perairan pantai yang jernih dengan substrat batu karang, karang mati dan benda bersifat massive yang berada di dasar perairan. Keberadaan Sargassum di perairan ikut membentuk ekosistem terumbu karang dan merupakan tempat asuhan bagi biota kecil. Kandungan koloid algin Sargassum bermanfaat sebagai bahan baku alginat dan industri.

NB. Banyak sumber bacaan.

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Phytochemicals

Phytochemicals

What are phytochemicals?
Phytochemicals are non-nutritive plant chemicals that have protective or disease preventive properties. There are more than thousand known phytochemicals. It is well-known that plant produce these chemicals to protect itself but recent research demonstrate that they can protect humans against diseases. Some of the well-known phytochemicals are lycopene in tomatoes, isoflavones in soy and flavanoids in fruits. They are not essential nutrients and are not required by the human body for sustaining life.

How do phytochemicals work?
There are many phytochemicals and each works differently. These are some possible actions:

•Antioxidant - Most phytochemicals have antioxidant activity and protect our cells against oxidative damage and reduce the risk of developing certain types of cancer. Phytochemicals with antioxidant activity: allyl sulfides (onions, leeks, garlic), carotenoids (fruits, carrots), flavonoids (fruits, vegetables), polyphenols (tea, grapes).
•Hormonal action - Isoflavones, found in soy, imitate human estrogens and help to reduce menopausal symptoms and osteoporosis.
•Stimulation of enzymes - Indoles, which are found in cabbages, stimulate enzymes that make the estrogen less effective and could reduce the risk for breast cancer. Other phytochemicals, which interfere with enzymes, are protease inhibitors (soy and beans), terpenes (citrus fruits and cherries).
•Interference with DNA replication - Saponins found in beans interfere with the replication of cell DNA, thereby preventing the multiplication of cancer cells. Capsaicin, found in hot peppers, protects DNA from carcinogens.
•Anti-bacterial effect - The phytochemical allicin from garlic has anti-bacterial properties.
•Physical action - Some phytochemicals bind physically to cell walls thereby preventing the adhesion of pathogens to human cell walls. Proanthocyanidins are responsible for the anti-adhesion properties of cranberry. Consumption of cranberries will reduce the risk of urinary tract infections and will improve dental health.

How do we get enough phytochemicals?
Foods containing phytochemicals are already part of our daily diet. In fact, most foods contain phytochemicals except for some refined foods such as sugar or alcohol. Some foods, such as whole grains, vegetables, beans, fruits and herbs, contain many phytochemicals. The easiest way to get more phytochemicals is to eat more fruit (blueberries, cranberries, cherries, apple,...) and vegetables (cauliflower, cabbage, carrots, broccoli,...). It is recommended take daily at least 5 to 9 servings of fruits or vegetable. Fruits and vegetables are also rich in minerals, vitamins and fibre and low in saturated fat.

Future of phytochemicals
Phytochemicals are naturally present in many foods but it is expected that through bioengineering new plants will be developed, which will contain higher levels. This would make it easier to incorporate enough phytochemicals with our food.

List of phytochemicals
======================
Alkaloids
•Caffeine
•Theobromine
•Theophylline

Anthocyanins
•Cyanidin
•Malvidin

Carotenoids
•Beta-Carotene
•Lutein
•Lycopene
.Coumestans

Flavan-3-Ols
Flavonoids
•Epicatechin
•Hesperidin
•Isorhamnetin
•Kaempferol
•Myricetin
•Naringin
•Nobiletin
•Proanthocyanidins
•Quercetin
•Resveratrol
•Rutin
•Tangeretin

Hydroxycinnamic Acids
•Chicoric acid
•Coumarin
•Ferulic acid
•Scopoletin

Isoflavones
•Daidzein
•Genistein

Lignans
•Silymarin

Monophenols
Hydroxytyrosol
Monoterpenes
•Geraniol
•Limonene

Organosulfides
•Allicin
•Glutathione
•Indole-3-Carbinol
•Isothiocyanates
•Sulforaphane

Other Phytochemicals
•Damnacanthal
•Digoxin
•Phytic acid

Phenolic Acids
•Capsaicin
•Ellagic Acid
•Gallic acid
•Rosmarinic acid
•Tannic Acid

Phytosterols
•Beta-Sitosterol

Saponins

Triterpenoids
•Ursolic acid

Xanthophylls
•Astaxanthin

Beta-Cryptoxanthin

Flavonoids

Description
Flavonoids are water soluble polyphenolic molecules containing 15 carbon atoms. Flavonoids belong to the polyphenol family. Flavanoids can be visualized as two benzene rings which are joined together with a short three carbon chain. One of the carbons of the short chain is always connected to a carbon of one of the benzene rings, either directly or through an oxygen bridge, thereby forming a third middle ring, which can be five or six-membered. The flavonoids consist of 6 major subgroups: chalcone, flavone, flavonol, flavanone, anthocyanins and isoflavonoids.
Together with carotenes, flavanoids are also responsible for the coloring of fruits, vegetables and herbs.

Distribution
Flavonoids are found in most plant material. The most important dietary sources are fruits, tea and soybean. Green and black tea contains about 25% percent flavonoids. Other important sources of flavonoids are apple (quercetin), citrus fruits (rutin and hesperidin),

Properties
Flavonoids have antioxidant activity. Flavonoids are becoming very popular because they have many health promoting effects. Some of the activities attributed to flavonoids include: anti-allergic, anti-cancer, antioxidant, anti-inflammatory and anti-viral. The flavonoids quercetin is known for its ability to relieve hay fever, eszema, sinusitis and asthma.
Epidemiological studies have illustrated that heart diseases are inversely related to flavonoid intake. Studies have shown that flavonoids prevent the oxidation of low-density lipoprotein thereby reducing the risk for the development of atherosclerosis.
The contribution of flavonoids to the total antioxidant activity of components in food can be very high because daily intake can vary between 50 to 500 mg.
Red wine contains high levels of flavonoids, mainly quercetin and rutin. The high intake of red wine (and flavonoids) by the French might explain why they suffer less from coronary heart disease then other Europeans, although their consumption of cholesterol rich foods is higher (French paradox). Many studies have confirmed that one or two glasses of red wine daily can protect against heart disease.
Tea flavonoids have many health benefits. Tea flavonoids reduce the oxidation of low-density lipoprotein, lowers the blood levels of cholesterol and triglycerides.
Soy flavonoids (isoflavones) can also reduce blood cholesterol and can help to prevent osteoporis. Soy flavonoids are also used to ease menopausal symptoms.

Research Reviews
A flavonoid fraction from cranberry extract inhibits proliferation of human tumor cell lines
Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop, May 31-June 1, 2005, Washington (USA)

Epicatechin

Description
Pure epicatechin is an odorless white powder. Epcatechin is a flavonol belonging to the group of flavonoids.

Distribution
Epicatechin is present in many plants. High quantities can be found in cocoa, tea and grapes.

Properties
Epicatechin is a strong antioxidant, has insulin mimic action and improves heart health. Dr. Norman Hollenberg of Harvard Medical School found that Kuna indians, who live on the San Blas Island Chain in Panama and drink high quantities of cocoa drinks, have a lower risk of stroke, heart failure, cancer and diabetes compored to the Indians living on the mainland. Dr. Norman Hollenberg even suggests to consider epicatechin as a vitamin.

Attenuation of diabetes
Studies show that epicatechin and other flavonoids exert a protective role on osmotic fragility of cells, similar to that of insulin. The mechanism of action of epicatechin is different to that of insulin and remains speculative. In diabetic red blood cells epicatechin causes an increase in acetylcholinesterase activity. This activity is significantly lower in type 2 diabetic patients.

Heart health
Epicatechin reduces lipid peroxidation and inhibits platelet aggregation. Epicatechin cause blood vessel dilation by regulating nitric oxide, a molecule secreted by the blood vessel endothelium to signal surrounding muscle to relax.

Research Reviews
Dietary Polyphenols and Health: Proceedings of the 1ste International Conference on Polyphenols and Health

Synonyms
(2R,3R)-2-(3,4-Dihydroxyphenyl) -3,4-dihydro-1(2H) -benzopyran-3,5,7-triol; cis-3,3',4',5,7-Pentahydroxyflavane; Epicatechol; epi-Catechin;epi-Catechol;

Ellagic Acid

Description
Ellagic acid is a fused four-ring polyphenol. Pure ellagic acid is a cream to light yellow crystalline solid.

Distribution
Ellagic acid is present in many red fruits and berries, including raspberries, strawberries, blackberries, cranberries, pomegranate and some nuts including pecans and walnuts. The highest levels of ellagic acid are found in raspberries. In plants ellagic acid is present in the form of ellagitannin, which is ellagic acid bound to a sugar molecule.

Properties
Ellagic acid has antioxidant, anti-mutagen and anti-cancer properties. Studies have shown the anti-cancer activity on cancer cells of the breast, oesophagus, skin, colon, prostate and pancreas. More specifically, ellagic acid prevents the destruction of P53 gene by cancer cells. Ellagic acid can bind with cancer causing molecules, thereby making them inactive. In their studie The effects of dietary ellagic acid on rat hepatic and esophageal mucosal cytochromes P450 and phase II enzymes. Ahn D et al showed that ellagic acid causes a decrease in total hepatic mucosal cytochromes and an increase in some hepatic phase II enzyme activities, thereby enhancing the ability of the target tissues to detoxify the reactive intermediates. Ellagic acid showed also a chemoprotective effect against various chemically induced cancers.
A study by Thresiamma KC and Kuttan R.Indian (Indian Journal Physiology and Pharmacology, 1996 October) indicate that oral administration of ellagic acid by rats can circumvent the carbon tetrachloride toxicity and subsequent fibrosis of the liver. Ellagic acid has also antiviral and antibacterial activities.
Facts about Ellagic Acid
Plants produce ellagic acid to protect themselves from microbiological infection and pests.

Research Reviews
Pomegranate Juice Ellagitannin Metabolites Are Present in Human Plasma and Some Persist in Urine for Up to 48 Hours
Chemoprevention of esophageal tumorigenesis by dietary administration of lyophilized black raspberries.

Synonyms
Benzoaric acid, eleagic acid, elagostasine, gallogen.

Curcumin

Description
Curcumin is a a water soluble orange-yellow coloured powder. Curcumin is one of three curcuminoids of turmeric. The other two curcuminoids are demethoxycurcumin and bisdemethoxycurcumin.

Distribution
Curcumin is obtained by solvent extraction from dried turmeric roots.

Properties
Curcumin has antioxidant, anti-inflammatory, antiviral and antifungal actions. Studies have shown that curcumin is not toxic to humans. Curcumin exerts anti-inflammatory activity by inhibition of a number of different molecules that play an important role in inflammation. Turmeric is effective in reducing post-surgical inflammation. Turmeric helps to prevent atherosclerosis by reducing the formation of bloods clumps.
Curcumin inhibits the growth of Helicobacter pylori, which causes gastric ulcers and has been linked with gastric cancers.
Curcumin can bind with heavy metals such as cadmium and lead, thereby reducing the toxicity of these heavy metals. This property of curcumin explains its protective action to the brain. Curcumin acts as an inhibitor for cyclooxygenase, 5-lipoxygenase and glutathione S-transferase.

Facts about Curcumin
Curcumin is used many foods as colouring, including mustard, margarine, processed cheese, cakes, curry powder, soft drinks and sweets.

Synonyms
1,7-Bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione, turmeric yellow

Coumarin

Description
Coumarin is a phytochemical with a vanilla like flavour. Coumarin is a oxygen heterocycle. Coumarin can occur either free or combined with the sugar glucose (coumarin glycoside).

Distribution
Coumarin is found in several plants, including tonka beans, lavender, licorice, strawberries, apricots, cherries, cinnamon, and sweet clover.

Properties
Coumarin has blood-thinning, anti-fungicidal and anti-tumor activities. Coumarin should not be taken while using anticoagulants. Coumarin increases the blood flow in the veins and decreases capillary permeability. Coumarin can be toxic when used at high doses for a long period

Facts about Coumarin
Coumarin seems to work as a pesticide in the plants that produce it. Coumarin is responsible for the sweet smell of new mown hay.

Synonyms
1,2-Benzopyrone, 2H-1-Benzopyran-2-one

Caffeine

Description
Caffeine is a water-soluble alkaloid. Pure caffeine is a white odourless crystalline powder with a very bitter taste. Caffeine is closely related to other alkaloids such as theophylline (mainly found in tea) and theobromine (mainly found in cacao beans). The difference between these three molecules is the position of the methyl groups.

Distribution
Caffeine is found in many everyday products, including tea, cola nuts, coffee, chocolate, mate and guarana. It is also found in some softdrinks (mainly colas and energy drinks) where it is artificially added.

Properties
Caffeine acts on the nervous system by blocking adenosine receptor thereby slowing down nerve cell acitivity. Caffeine stimulates the central nervous system, respiration and blood circulation. Caffeine also acts as a diuretic. Caffeine increases the circulation and oxidation of fatty acids. This is why caffeine is used by sportsmen to increase fatty acid metabolism. Caffeine is often used in combination with aspirin to treat headaches. Caffeine can also have negative impact on health, especially if overdosed. There is evidence that too much caffeine can reduce bone density and caffeine is not recommended for pregnant women. Moderation is the key to caffeine consumption.

Facts about Caffeine
Caffeine containing plants have been used by different cultures over centuries. Tea from caffeine containing plants was used to treat headaches, coughs and even plague. Only recently caffeine is used to stay awake and relieve fatigue. Caffeine is now one of the most widely used phytochemical.
Caffeine is not addictive but it can be habbit forming. Although caffeine is not toxic to humans in normal levels, it is very toxic to animals, such as dogs and horses.

Synonyms
1,3,7-Trimethylxanthin

Beta-Sitosterol

Description
Beta-sitosterol is a phytosterols or plant sterol. The structure of beta-sitosterol is similar to that of cholesterol. Beta-sitosterol differs from cholesterol by the presence of an extra ethyl group

Distribution
There are many plant sources of beta-sitosterol, but the most important are wheat germ, rice bran, flax seeds, peanuts, soybeans, pumpkin seeds and corn oil. Muli and co-workers showed that a plant-based diet, rich in fibre, soy and flax seed, can increase serum levels of beta-sitosterol.

Properties
Beta-sitosterol is mainly known and used for its cholesterol lowering property. But studies have shown that the phytochemical may have other health benefits: easing symptoms of benign prostatic enlargement, reducing risk of cancer and prevention of oxidative damage through its antioxidant activity.

Anti-cancer
Epidemiological and experimental studies have suggested a protective role of beta-sitosterol in the development of some types of cancer such as breast, colon and prostate cancer. In-vivo studies have shown that the phytochemical inhibited proliferation and induce apoptosis in human solid tumors such as colon and breast cancers. The studies about the protective effect of beta-sitosterol on breast cancer only involved in-vitro experiments using cultured breast cancer cells. These studies clearly show that the phytochemicals kills breast cancer cells and is not toxic to normal cell. Clinical studies linking beta-sitosterol and breast cancer are still missing but some scientists suggest that it may improve the efficiency of tamoxifen, a drug often used to treat breast cancer.

Antioxidant
Beta-sitosterol is an antioxidant able to reduce DNA damage, reduce the level of free radical in our cells and to increase the level of typical antioxidant enzymes.

Atherosclerosis
Regular intake of beta-sitosterol may reduce blood cholesterol levels by directly inhibiting the absorption of cholesterol. Beta-sitosterol also prevents the oxidation of LDL cholesterol thereby reducing the risk of atherosclerosis.

Prostate enlargement
Clinical studies have confirmed the beneficial effects of beta-sitosterol in patients with prostate enlargement. The phytochemical decreases post-void residual urinary volume and increases urinary flow rate in these patients.

Synonyms
(3beta)-stigmast-5-en-3-ol, 22:23-dihydrostigmasterol, alpha-dihydrofucosterol, cinchol, cupreol, rhamnol, quebrachol and sitosterin.

Beta-Carotene

Description
Beta-carotene is the most common form of carotene and belongs to the group of terpenoids. Pure beta-carotene is red to purple colored oil. It is not soluble in water. Beta-carotene which is used in drinks is encapsulated with starch or gelatin to make it soluble.

Distribution
Beta-carotene occurs in colored fruits and vegetables such as mango, apricot, sweet potatoes, carrots, kale, broccoli, spinach, turnip greens, winter squash and collard greens.

Properties
Beta-carotene has received a lot of attention as potential anti-cancer and anti-aging phytochemical. Beta-carotene is a powerful antioxidant, protecting the cells of the body from damage caused by free radicals. Studies indicate that diets low in beta-carotene can increase the body's susceptibility to damage from free radicals, resulting in an increased risk of chronic diseases like heart disease and cancers. Beta-carotene supplements may help reduce sun induced skin damage. Smokers should avoid large doses of beta carotene supplements. Beta-carotene is one of the many carotenoids that our body can convert into vitamin A (retinol).

Anti-cancer
Beta-carotene acts as an anti-cancer agent through its antioxidant property but it also seems to stimulate cell to cell communication. Poor communication between cells may eventually lead to cancer. However, beta-carotene may cause adverse effects on smokers. Two studies indicate that heavy smokers and drinkers may have an increased risk of lung cancer or heart disease, when taking daily more than 20 mg synthetic beta-carotene as supplements. A study by Harvard School of Public Health published in January 2004 issue of Cancer Epidemiology Biomarkers and Prevention indicates that beta-carotene consumed as part of natural foods has no such negative effects.

Skin protection
Studies have demonstrated that beta-carotene may be used for skin protection: it reduces UV-induced redness of the skin and improves melasma. Beta-carotene is often use in supplements or topical creams to protect our skin. Too much intake of beta-carotene can result in carotenodermia, a condition that shows a yellowish discoloration of the skin. This is reversible and harmless.

Heart health
Epidemiological studies show that beta-carotene may improve our heart health by decreasing blood pressure. Beta-carotene may also help to prevent arteriosclerosis by inhibiting the oxidation of lipids.

Facts about Beta-Carotene
Beta-Carotene is a yellow pigment naturally occurring in fruits and vegetables. It also known as a provitamin because it can be converted in our body into vitamin A after oxidative cleavage by beta-carotene 15, 150-dioxygenase. In plants, beta-carotene, acts as an anti-oxidant and neutralizes singlet oxygen radicals formed during photosynthesis. Cooking improves the availability of carotenoids in foods. However, prolonged cooking should be avoided to prevent the formation of change of beta-carotene into the cis-configuration.

Synonyms
Pro-vitamin A

Astaxanthin

Description
Astaxanthin is a red carotenoid pigment. Astaxanthin is similar in structure than beta-carotene. The small differences in structure causes large differences in the chemical properties

Distribution
Astaxanthin is produced by microscopic small plants: the micro-alga Haematococcus pluvialis. Haematococcus algae can contain up to 30 g of astaxanthin per kg dried algae. These micro-alga are eaten by marine animals including fish, crawfish, crabs and lobster. The Astaxanthin is responsible for the red colour of these animals. Another commercial source is from the ink coloured yeast Xanthophyllomyces dendrorhous.

Properties
Astaxanthin is a powerful antioxidant. The free radical scavenging activity of astaxanthin protects lipids from peroxidation and reduces oxidative damage of LDL-cholesterol (thereby reducing arterial plaque formation), cells, cell membranes, mitochondrial membranes. Astaxanthin increases strength and endurance.
Astaxanthin seems to improve the immune system by increasing the number of antibody producing cells. Astaxanthin enhances antibody production by exerting actions on T-cells and T-helper cells. Astaxanthin is used to treat neurodegenerative conditions such as Alzheimer's and Parkinson?s disease.
Astaxanthin protects the eyes and skin from sun radiation damage by quenching singlet and triplet oxygen. Studies with rats show that astaxanthin reduces retinal injury.
Studies have shown the anti-cancer effects of astaxanthin in rodents. The inhibitory effect of astaxanthin on cancer is stronger han that of beta-carotene.

Facts about Astaxanthin
Most Astaxanthin is not extracted from the marine plants but is chemically produced. In commercial fish and crustacean farms, chemically produced astaxanthin is added to feeds in order to improve the colour.

Synonyms
3,3'-Dihydroxy-b,b-carotene-4,4'-dione

Allicin

Description
Allicin is garlic's defence mechanism against attacks by pests. When the garlic plant is attacked or injured it produces allicin by an enzymatic reaction. The enzyme alliinase, converts the chemical alliin to allicin, which is toxic to insects and microorganisms. The antimicrobial acivity of allicin was discovered in 1944 by Cavallito. Purified allicin is not sold commercially because it is not stable and has an offensive odour. Allicin extracted from garlic loses its beneficial properties within hours and turns into other sulphur containing compounds. Diallyl trisulfade, which is similar to allicin but is chemically produced, is stable and is used for treatment bacterial, fungal and parasitic infections.

Distribution
Allicin is the predominant thiosulfinate in garlic (Allium sativum). Allicin is the chemical responsible for the typical and offensive odor of garlic.

Properties
The antimicrobial effect of allicin is due to its chemical reaction with thiol groups of various enzymes.
The incidence of gastric ulcers is lower in populations with high garlic intake. Studies have confirmed that allicin has inhibitory activity on Helicobacter pylori, a bacteria responsible for the development of gastric ulcers. The sensitivity of Helicobacter pylori to allicin might also explain the lower risk of stomach cancer in people with high garlic intake. A study by Ankri et al (1997) demonstrated that allicin inhibited the ability of the parasite Entamoeba histolytica to destroy monolayers of baby hamster kidney cells.
Allicin is not bioavailable and will not get absorbed in the blood, even after ingesting large amounts of allicin.

Research Reviews
Intake of Garlic and its Bioactive Components
The influence of heating on the anticancer properties of garlic.
Pharmacologic activities of aged garlic extract in comparison with other garlic preparations.

Synonyms
Diallyl thiosulfinate

Geraniol

Distribution
Bergamot, carrot, coriander, lavender, lemon, lime, nutmeg, orange, rose, blueberry and blackberry.

Properties
Geraniol is a natural antioxidant. Geraniol has been suggested to help prevent cancer. Carnesecchi S. et al demonstrated in his study "Geraniol, a component of Plant Essential Oils, Inhibits Grwoth and Polyamine Biosyntehsis in Human Colon Cancer Cells", (Pharmacology, July 2001) that geraniol caused a 50% increase of ornithine decarboxylase activity, which is enhances during cancer growth. Geraniol inhibits DNA synthesis.
Burk YD concluded in his study "Inhibition of Pancreatic Cancer Growth by the dietary isoprenoids farnesol and geraniol" (Lipids, February 1997) that geraniol, farnesol and perilll alcohol suppress pancreatic tumor growth.
Other animal studies have also demonstrated the anticancer effects of geraniol.

Facts about Geraniol
Geraniol is mainly used in perfumery and flavouring.

Synonyms
Lemonol, beta-Geraniol, trans-3,7-Dimethyl-2,6-octadien-1-ol

Hydroxytyrosol

Description
Hydroxytyrosol is believed to be the antioxidant with the highest free radical scavenging capacity: double that of quercetin and more than 3 times that of epicatechin. The wastewaters generated during olive processing contain a high levels hydroxytyrosol, most of which can be recovered to produce hidroxytyrosol extracts. Studies by Visioli et al (2000) showed that a low dose of hydroxytyrosol reduces the consequences of sidestream smoke-induced oxidative stress in rats.

Distribution
Hydroxytyrosol is the main polyphenol found in olives.

Properties
Hydroxytyrosol has the same health promoting properties than other polyphenols: prevention of atherosclerosis, promotion of intestinal and respiratory health and prevention of cancer. Hydroxytyrosol also reduces the oxidative stress caused by smoking.

Abstracts
Benefits of Hydroxytyrosol
In Vivo Studies about Antioxidant Properties of Hydroxytyrosol
In Vitro Studies about Antioxidant Properties of Hydroxytyrosol
Cancer and Hydroxystyrosol
Influence of Hydroxystyrol on Heart Disease

Indole-3-Carbinol

Description
Pure indole-3-Carbinol is an off-white solid belonging to the group of indoles. Indole-3-carbinol is only formed in these vegetable after crushing or during cooking.

Distribution
The phytochemical indole-3-carbinol is found in cruciferous vegetables such as cabbage, cauliflower, broccoli, kale and brussels sprouts. Indole-3-carbinol is made from indole-3-glucosinolate by the enzyme myrosinase. This enzyme is only activated after maceration of the vegetables.

Properties
Indole-3-carbinol and its main metabolite diindoylmethane modulates several nuclear transcription factors resulting in a variety of biological and biochemical effects. Indole-3-carbinol works as a strong antioxidant, thereby protecting the DNA and other cell structures.

Chemopreventive
Indole-3-carbinol has chemopreventive activity and stimulates the production of detoxifying enzymes. The phytochemical protects against carcinogenic effect of pesticides and other toxins.

Anticancer
The anticancer effects of indole-3-carbinol and its metabolite diindoylmethane are the result of specific activities: inducing enzymes that metabolize carcinogens, enhancing DNA repair, inducing G1 cell cycle arrest and apoptosis. Indole-3-carbinol blocks estrogen receptor sites on the membranes of breast and other cells, thereby reducing the risk of cervical and breast cancer. Indole-3-carbinol increases the ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone and inhibits the 4-hydroxylation of estradiol. This is a favourable action of indole-3-carbinol because 16 alpha-hydroxyestrone and 4-hydroxyestrone have carcinogenic action. The estrogen metabolite 2-hydroxyestrone has protective against several types of cancer. Studies with animals have demonstrated that indole-3-carbinol reduced the carcinogenic affects of aflatoxins. The influence of indole-3-carbinol on the development of prostate cancer is less clear. Most studies report protective effects but a few studies indicate that indole-3-carbinol may promote prostate cancer formation. Treatment of skin cancer cells with ultraviolet-B results in the apoptosis of their apoptosis, a favorable effect that seems to be stimulated by indole-3-carbinol. Some studies also show a beneficial effect on the treatment of skin cancer.
Heart health
A few studies demonstrate the beneficial effects of indole-3-carbinol on lipid synthesis and platelet aggregation, suggesting that this phytochemical could help to improve heart health.

Synonyms
I3C, 3-hydroxymethyl indole, 3-indole methanol

Limonene

Description
Pure limonene is a clear liquid. Limonene is a monoterpene, made up of two isoprene units. Limonene occurs in two optically active forms, l-limonene and d-limonen. Both isomers have different odours: l-limonene smells piney and turpentine like and d-limonene has a pleasing orange scent.

Distribution
Limonene is found in the essential oils of citrus fruits and many other plant species. Industrial limonene is produced by by alkali extraction of citrus residues and steam distillation. This distillate contains more than 90% d-limonene.

Properties
Studies have shown that limonene have anti- cancer effects. Limonen increase the levels of liver enzymes involved in detoxifying carcinogens. The Glutathione S-transferase (GST) is a system which eliminates carcinogens. Limonene seems to promote the GST system in the liver and small bowel, thereby decreasing the damaging effects of carcinogens. Animal studies demonstrated that dietary limonene reduced mammary tumor growth.

Facts about Limonene
Limonene is also used as a solvent and cleaner. It can replace white spirit and other solvents.

Synonyms
Methyl-4-isopropenyl cyclohexene, Cajaputene, Carvene, Cinene, Dipentene, Efchole

Lutein

Description
Lutein is an antioxidant, which belongs to the carotenoid family. Lutein is a yellow coloured pigment. Although lutein is not categorized as a vitamin, dietary lutein is believed to be an essential nutrient for normal vision. Because lutein is fat soluble, a deficiency may occur if fat digestion is impaired.

Distribution
Lutein is found in egg yolk and many plants and vegetables, including red peppers, mustard, broccoli, zucchini, corn, garden peas, spinach, leek, collard greens and kale. Lutein is responsible for the colouring of many fruits and vegetables.

Properties
Lutein is an antioxidant which is believed to be an essential nutrient for normal vision. The protective role of lutein against eye damage is well document. Studies have also indicated that lutein improves heart health, protects our skin against UV damage, reduces diabetes induced oxidative stress, and possesses anti-inflammatory and anti-cancer properties.

Eye protection
The central part of the retina, called the macula, contains macular pigments in which lutein is concentrated. The yellow coloured pigments protect the retina from damage of the photo-oxidative affect of high-energy light. Lutein offers eye protection by lowering the risk of age related vision loss, which causes gradual loss of central vision. Age related vision loss or age related macular degeneration is caused by steady damage of the retina.

Heart health
Lutein can also reduce the risk for artery diseases. Studies have shown that persons with the highest lutein intake showed the lowest artery wall thickening. Lutein also reduces the oxidation of LDL cholesterol thereby reducing the risk of artery clogging.

Skin protection
Lutein can also reduce the risk of skin cancer and sunburn. Under influence of sunlight, free radicals are formed inside the skin. These free radicals can damage the DNA of cells. Lutein can protect against the damaging effects of UV-B radiation.

Lycopene

Description
Lycopene belongs to the family of carotenoids. It has a structure that consists of a long chain of conjugated double bonds, with two open end rings. The structure lycopene is the longest of all carotenoids

Distribution
Lycopene is the red pigement of ripe tomatoes. Tomatoes contribute over 85% of the lycopene intake by women (Chug-Ahuja, 1993). Lycopene is also found in guava, pink grapefruit, red oranges and watermelon

Properties
Lycopene is a very efficient antioxidant, which can neutralize oxygen derived free radicals. The oxidative damage caused by these free radicals has been linked to many degenerative diseases such as cardiovascular diseases, premature aging, cancer and cataracts. In many countries it is legally allowed to advertise foods containing tomato lycopene as "containing antioxidants for the maintenance and support of healthy cells". Lycopene is generally known for its protective action against prostate cancer.

Anti-cancer
In vitro-studies have shown the anti-cancer properties of lycopene against many cancer cells, including cancer cells of prostate, stomach, lung, colon and skin. There are numerous studies about the effect of lycopene on cancer and prostate cancer in particular. Using Pubmed as a retrieval base, more than 80 scientific studies have the names lycopene and prostate in their title. Most of the in-vitro experiments using cultured prostate cancer cells demonstrate a protective effect. However, most literature review studies or clinical studies are less conclusive and often contradictory. Lycopene also shows anti-mutagenic action against chemically induced DNA damage.

Antibacterial and antifungal
Lycopene possesses antibacterial and antifungal properties. Lycopene can help to reduce inflammation of the gums and can help to fight infections of Candida albicans.

Diabetes
Diabetes patients may suffer from complications as vascular disease, diabetic neuropathies or infections. Lycopene helps to protect diabetes patients against cardiovascular disease and may improve the immune response.
However, the consumption of lycopene seems not to reduce the risk of diabetes mellitus type 2.

Antioxidant
Lycopene has a structure similar to that of the well-known antioxidant beta-carotene, but its antioxidant activity is much stronger. Treatment of cells will lycopene protects cells against DNA damage and lipid peroxidation.

Arteriosclerosis
Lycopene inhibits platelet aggregation and reduces the production of foam cells which play an important role in the development of arteriosclerosis. Lycopene helps to prevent arteriosclerosis by reducing inflammatory agents in rats increased risk of venous thrombosis.

Antitoxic
In laboratory conditions, lycopene shows antitoxic properties against many toxins such as aflatoxin, cyclosporine and cadmium.

Phytic acid

Description
In plants phytic acid is the principal store of phosphate. Phytic acid is a natural plant antioxidant

Distribution
Phytic acid can be found in most grains, seeds and beans. Rich sources of phytic acid are wheat bran and flaxseed (3 % phytic acid).

Properties
Phytic acid has been considered as an anti-nutritional component in cereals, seeds and beans. Research has traditionally focused on its structure that gives it the ability to bind minerals, proteins and starch, and the resulting lower absorption of these elements. However, resent research have shown that phytic acid has many health benefits. Phytic acid has antioxidant, anticancer, hypocholesterolemic and hypolipidemic effects.

Anticancer effect of phytic acid
In animal studies phytic acid showed a protective action in carcinogenesis. This action could be explained by its mineral chelating potential. Some studies suggest that phytic acid acts as anti-cancer agent by reversing the proliferative effects of carcinogens.

Benificial for diabetic patients
Phytic acid may have health benefits for diabetes patients. It lowers blood glucose response by reducing the rate of starch digestion and slowing the gastric emptying.

Other effects
Phytic acid releases inositol that during digestion. Although inositol is not an essential nutrient it might reduce depressions. Studies also show that phytic acid may reduce inflammation.

Synonyms
Inositol-phosphate

Quercetin

Description
Quercetin is the most abundant of the flavonoids. Quercetin belongs to the flavonoids family and consist of 3 rings and 5 hydroxyl groups. Querctin is also a building block for other flavonoids. Quercetin occurs in food as a aglycone (attached to a sugar molecule). Only a small percentage of the ingested quercetin will get absorbed in the blood.

Distribution
Quercetin is found in many common foods including apple, tea, onion, nuts, berries, cauliflower and cabbage.

Properties
Quercetin has many health promoting effects, including improvement of cardiovascular health, reducing risk for cancer. Quercetin has anti-inflammatory and anti-allergic effects. All these activities are caused by the strong antioxidant action of quercetin. It will help to combat free radicals molecules, which can damage cells.
As many other flavonoids, quercetin prevents the oxidation of LDL (bad) cholesterol.
The anti-inflammatory action of quercetin is caused by the inhibition of enzymes, such as lipoxygenase, and the inhibition of inflammatory mediators. Quercetin also inhibits the release of histamine, which causes congestion, by basophils and mast cells.
Studies have shown that quercetin reduces the cancer risk of prostate, ovary, breast, gastric and colon cells.
Quercetin also seems to reduce the production of uric acid, by inhibiting the xanthine oxidase, thereby easing gout symptoms.
Studies have shown an improved lung function and lower risk of certain respiratory diseases (asthma and bronchitis) for people with high apple (rich in quercetin) intake.

Research Reviews
Dietary Intakes of Flavonols, Flavones and Isoflavones by Japanese Women and the Inverse Correlation between Quercetin Intake and Plasma LDL Cholesterol
Concentration

Tissue Distribution of Quercetin in Rats and Pigs
The Effect of Quercetin on SW480 Human Colon Carcinoma Cells: a Proteomic StudyQuercetin inhibits eNOS, microtubule polymerization, and mitotic progression in bovine aortic endothelial cells.
Rat Gastrointestinal Tissues Metabolize Quercetin

Resveratrol

Description
Resveratrol is a flavonol belonging to the group of flavonoids. It is produced by the plant as a defence against diseases.

Distribution
Resveratrol is present in many plants and fruits, including red grapes, eucalyptus, spruce, blueberries, mulberries, peanuts, giant knotweed. Also red wine contains a lot of it. The longer the grape juice is fermented with the grape skins the higher the resveratrol content will be.

Properties
Resveratrol is an antioxidant but its antioxidant properties are weaker that those of quercetin and epicatechin. It has anticancer properties and inhibits lipid peroxidation of low-density lipoprotein and prevents the cytotoxicity of oxidized LDL. Resveratrol also increases the activity of some antiretroviral drugs in vitro.

Antioxidant
In vitro studies have shown that resveratrol inhibits the oxidative damage caused by the heavy metal cadmium. The antioxidant activity of resveratrol reduces damage to endothelial cells exposed to nitrite radicals and protects skin cells against damage caused by UV radiation.

Anticancer
The antioxidant action of resveratrol helps to prevent damage to DNA but it also influences the transcriptions of genes responsible for redox metabolism and inhibits proliferartion of cancer cells. Resveratrol appears to decrease tumor promotion activity by inhibiting the enzyme cyclooxygenase-1, which converts arachidonic acid to substances that promote tumor growth.

Benefits for diabetes
Resveratrol may be benificial for diabetes. Administration of resveratrol may protect against oxidative damage caused by high glucose levels. It also reduces diabetic neuropathic pain.

Heart health
Resveratrol protects our heart and blood vessels by directly scavenging oxidants, which could cause oxidation of lipids, and by preventing apoptosis of endothelial cells. It may also help to prevent heart damage after a cardiac arrest. Reduced platelet aggregation has been attributes to resveratrol, thereby reducing the risk of atherosclerosis.

Increase of lifespan
Tests with animals have shown that that high food intake reduces lifespan. One study showed that resveratrol was able to able to increase the life span of mice on a high calorie diet.

Antitoxic
Many studies on animals have shown antitoxic effects of resveratrol. Resveratrol was able to reverse damages caused by the administration of the chemotherapeutic drug bleomycin. Resveratrol also helped to reduce brain damage and oxidative damage of the liver during ethanol intoxication. It also reduced kidney damage of rats treated with the antibiotic gentamicin.

Facts about Resveratrol
Resveratrol explains partly the French Paradox: the low incidence of heart disease among French people, who eat relatively a lot of unhealthy fat but drink resveratrol containing red wine.

Research Reviews
Resveratrol Promotes Clearance of Alzheimer's Disease
Resveratrol Inhibits TNF-alpha?Induced Proliferation and Matrix Metalloproteinase Expression in Human Vascular Smooth Muscle Cells

Synonyms
Trans-3,5,4'-trihydroxystilbene

Rutin

Description
Rutin is a bioflavonoid. Pure rutin is yellow or yellow-green colored needle-shaped crystal. Rutin is a flavonol glycoside comprised of the quercetin and the disaccharide rutinose (rhamnose and glucose).

Distribution
Rutin is found in many plants, fruits and vegetables. The richest source is buckwheat. Rutin is also found in citrus fruits, noni, black tea, apple peel. During digestion much of the rutin is metabolized to its aglycone, quercetin.

Properties
Rutin has strong antioxidant properties. Rutin has also the property to chelate metal ions, such as iron, thereby reducing the Fenton reaction (production damaging oxygen radicals). Rutin also seems to stabilize vitamin C. If rutin is taken together with vitamin C, the activity of ascorbic will be intensified.
Rutin is important because it strengthens capillaries and can help people who bruise or bleed easily. Studies have demonstrated that rutin can help to stop venous edema, that is an early sign of chronic venous disease of the leg.
Rutin has anti-inflammatory effects. Animal studies have shown that rutin has preventive and healing effects.
There are indications that rutin can inhibit some cancerous and pre-cancerous conditions.
Rutin may help to prevent atherogenesis and reduce the cytotoxicity of oxidized LDL-cholesterol.

Synonyms
Rutoside, quercetin-3-rutinoside and sophorin

Silymarin

Description
Silymarin is a polyphenolic flavonoid derived from milk thistle. Silymarin consists of three phytochemicals: silybin, silidianin and silicristin. Silybin is the most active phytochemicals and is largely responsible for the claimed benefits of silymarin.

Distribution
Simylarin is found in milk thistle.

Properties
Silmarin is a antioxidant or free radical scavenger. Skin care products often contain silymarin because it antioxidant activity may reduce the risk for skin cancer risk. Silymarin provides protection against different stages of UVB-induced carcinogenesis. Silymarin protects the liver by promoting the growth of new liver cells. By inhibiting lipid peroxidation silymarin helps to reduce or prevent liver damage caused by alcohol, poisonous mushrooms, drugs and other toxins. Silymarin also helps with the digestion of fats.
Silymarin is also used against HIV but there?s no evidence that silymarin is effective.
Studies indicate that silymarin decreasing endogenous insulin overproduction and the need for exogenous insulin administration. Silymarin has also anti-atherosclerotic activity, by inhibiting the expression of adhesion molecules.
Pharmacological studies show that silymarin is not toxic.

Abstracts
Health Benefits of Silymarin
Synonyms
Silibinin

Theobromine

Description
Theobromine is an alkaloid belonging to the methylxanthines. The structure of theobromine is similar to that of caffeine.

Distribution
Theobromine is mainly found in cocoa beans (about 25 g/kg), and consequently in chocolate. Theobromine levels are highest in dark chocolates (about 10 g/kg). Milk chocolates contains about 2 to 5 g theobromine per kg. (1-5 g/kg). Theobromine is also present in tea and cola nuts.

Properties
Theobromine has a similar effect than caffeine, but about 10 times weaker. Theobromine has diuretic, stimulant and relaxing effects. Theobromine can lower the blood pressure because it can to dilate blood vessels.
Theobromine has stimulant properties, similar to caffeine. Unlike caffeine theobromine does not affect the central nervous system.
Theobromine can also relax bronchi muscles in the lungs. Theobromine can be used as cough medicine. Studies indicate that theobromine acts on the vagus nerve, which runs from the lungs to the brain.

Facts about Theobromine
Although theobromine does not cause harmful effects with humans, it is highly toxic to some domestic animals, including dogs and horses. With the animals, theobromine can lead to cardiac arrhythmias and seizures.
Theobromine has a bitter flavour, which gives dark chocolate its typical bitter taste.

Synonyms
3,7-dimethylxanthine, 3,7-dihydro-3,7-dimethyl-1H-purine-2,6-dione

Ursolic acid

Description
Ursolic acid is a is a pentacyclic triterpenoid.

Distribution
Ursolic acid is present in many plants, including apples, bilberries, cranberries, elder flower, peppermint, lavender, oregano, thyme, hawthorn, prunes.

Properties
Ursolic acid has medicinally action, both topically and internally. Ursolic acid is used in many cosmetic preparations for its anti-inflammatory, antitumor and antimicrobial properties.
Ursolic acid has antibacterial and antifungal activity. Tests have shown that Ursolic acid inhibits the growth of Candida albicans and Microsporium lenosum.
Ursolic acid has anti-inflammatory properties and is used in ointments to treat burns.
Topical application of ursolic acid inhibited TPA-induced initiation and promotion of tumor growth.

Synonyms
Malol, micromerol, urson, prunol, (3b)-3-hydroxyurs-12-en-28-oic acid

Hesperidin

Description
Hesperidin is a flavanone glycoside consisting of the flavone hesperitin bound to the disaccharide rutinose. The sugar cause hesperidin to be more soluble than hesperitin.

Distribution
The phytochemical hesperidin is mainly found in citrus fruits such as lemons and oranges. The highest concentration of hesperidin can be found in the white parts and pulps of the citrus peels. Hesperidin can also be found in green vegetables.

Properties
Hesperidin has antioxidant, anti-inflammatory, hypolipidemic, vasoprotective and anticarcinogenic and cholesterol lowering actions. Hesperdin can inhibit following enzymes: phospholipase A2, lipoxygenase, HMG-CoA reductase and cyclo-oxygenase.
Hesperidin improves the health of capillaries by reducing the capillary permeability.
Hesperidin is used to reduce hay fever and other allergic conditions by inhibiting the release of histamine from mast cells. The possible anti-cancer activity of hesperidin could be explained by the inhibition of polyamine synthesis.
A study 'Hesperidin, a citrus flavonoids, inhibits bone loss and decreases serum and hepatic lipids in ovariectomized mice' by Hiroshige Chiba et al (J. Nutrition, June 2003) showed that hesperidin added to the died not only lowered serum and hepatic cholesterol, but also inhibited bone loss by decreasing osteoclast number in ovariectomized mice. The molecular mechanism of the inhibitory effect of hesperidin on bone resorption is not clear.

Synonyms
Hesperetin 7-rhamnoglucoside, hesperetin-7-rutinoside

Isorhamnetin

Description
Isorhamnetin is a flavonoid, which occurs naturally in plants, but is also a metabolite of quercetin (isorhamnetin is methylated quercetin).

Distribution
Red turnip, goldenrod, mustard leaf, ginkgo biloba.

Properties
Isorhamnetin is not that much studied than quercetin. However, the few that exist indicate that isorhamnetin has similar health benefits: it may reduce the risk of cancer, improve heart health and ease diabetes complications.

Anti-cancer
The anti-cancer effect of isorhamnetin has been demonstrated in in-vivo and in-vitro tests. In-vitro tests with lung cancer cells, liver cancer cells and esophageal cancer cells showed that isorhamnetin induces apoptosis of these cells. An in-vivo experiment with mice that were injected with isorhamnetin showed a reduced tumor weight.

Heart health
Both quercetin and isorhamnetin help to improve heart health. They improve the endothelial function through their antioxidant action and reduce the oxidation of HDL, resulting in a decreased risk of arteriosclerosis. Isorhamnetin is a potential candidate to explain the reduction of blood pressure and vascular protective effects observed in animal models of hypertension.

Diabetes complications
Some studies have focused on the ability of isorhamnetin to attenuate diabetes complications, such as diabetic cataract, lipid peroxidation and high blood glucose levels.

Synonyms
3,5,7-Trihydroxy-2-(4-hydroxy-3-metoxyphenyl)benzopyran-4-on; 3,5,7-Trihydroxy-2-(4-hydroxy-3-
methoxyphenyl)-4H-1-benzopyran-4-one

Myricetin

Description
Myricetin is flavonol, consisting of 3-hydroxyflavone backbone and 6 hydroxyl groups. Pure myricetin is a yellow-beige powder crystalline powder. Myricetin mainly occurs in nature in the form of glycosides.

Distribution
Myricetin is found in several foods such as walnuts, onions, berries, herbs and red grapes.

Properties
Myricetin exerts a wide variety of biological effects, including antioxidant and free radical-scavenging activities. Reports indicate that myricetin has anti-cancer and anti-inflammatory properties and may improve bone-health.

Anticancer
Myricetin has strong anticancer and antimutagenic properties, but it has been shown to promote mutagenesis with the use of the Ames Test. Although the anticancer property of myricetin has been attributed mainly to its antioxidant action, it has additional protective mechanisms.

Anti-inflammatory
Myricetin has been shown to inhibit the expression of tumor necrosis factor-alpha, a cytokine that promotes the inflammatory response and is involved in inflammatory diseases. Myricetin glucuronide is an inhibitor of lipoxygenase 5-LOX and cyclooxygenases COX-1 and Cox-2.

Heart health
Myricetin and other flavonoids may improve heart health by prevening LDL oxidation and reducing the uptake of oxidized LDL by macrophages.

Diabetes
Studies showed that myricetin inhibits the uptake of methylglucose by adipocytes, reduces oxidative injury in diabetes related bone diseases and reduces glucose plasma level in diabetic rats.

Brain health
Myricetin may offer benefits to person with brain diseases such as Parkinson and Alzheimer's. Myricetin inhibits ROS production caused by glutamate and reduces glutamate-induced activation of caspase-3. Myricetin restored dopamine level in laboratory animals with induced Parkinsonism. Myricetin may also inhibit beta-amyloid fibril formation in Alzheimer patients.

Synonyms
3,3',4',5,5',7-hexahydroxyflavone, Cannabiscetin, Myricetol, Myricitin

Naringin

Description
Naringin belongs to the group of flavonoids. Pure naringin is a yellowish powder. Naringin is a conjugate of a sugar molecule with naringenin. The structure of naringin is very similar to that of hesperidin.

Distribution
Naringin is mainly found in grapefruits. It is the compound that gives grapefruit its typical bitter flavour.

Properties
Naringin has antioxidant, anti-carcinogenic and cholesterol lowering activity.
Studies have shown that naringin has a cholesterol-lowering effect, reduces LDL oxiation and can help to prevent hypercholesterolemia. Gorinstein S et al of the The Hebrew University-Hadassah Medical School, Jerusalem, studied the changes in plasma lipid and antioxidant activity in rats as a result of naringin and red grapefruit supplementation. They found that diets supplemented with red grapefruit juice and to a lesser degree with naringin improved the plasma lipid levels mainly in rats fed cholesterol and increased the plasma antioxidant activity. They concluded that naringin has plasma lipid lowering and plasma antioxidant activity increasing activity.
Naringin is an aldose reductase inhibitor which means that it can help to fight retinal disease linked to diabetics.
Naringin (and grapefruit) can interfere with certain drugs including calcium channel blockers, sedatives, cholesterol lowering drugs, caffeine and estrogen. Naringin stimulates the effect of caffeine and could therefore increase its fat burning action.

Synonyms
4,5,7-Trihydroxyflavanone 7-rhamnoglucoside, Naringenin-7-neohesperidoside

Nobiletin

Description
Nobiletin is a citrus flavonoids with a structure similar to that of tangeretin. It has the typical flavonoid structure and contains 6 methoxyl groups, one more than tangeretin. This high level of methoxylation increases the hydrophobic character of tangeretin. Pure nobiletin has the appearance of colorless needles and has a bitter taste.

Distribution
Peels of citrus fruits.

Properties
Nobiletin seems to be a very noble phytochemical with many potential health benefits. The most studied properties of nobiletin are its anti-inflammatory and anti-cancer activities. Nobiletin also helps to lower cholesterol levels and some studies indicate that it may improve impaired memory loss and treat acne.

Anti-inflammatory
Numerous in-vivo and in-vitro studies have demonstrated the anti-inflammatory activity of nobiletin and its metabolites. Nobiletin acts directly as an antioxidant but also interferes with biological inflammatory processes. It inhibits the expression of genes involved in inflammation by blocking the binding of NF-kappaB with DNA. One study showed that nobiletin reduced airway inflammation of asthmatic rats. Treatment of skin cells with nobiletin also reduced inflammation caused by ultraviolet-B radiation.

Anti-cancer
The anti-cancer properties of nobiletin are supported by many scientific studies. Nobiletin act by its antiproliferation effect without being toxic to normal cells. Favourable results have been obtained on cancer cell lines of the liver, stomach, prostate and colon.

Cholesterol lowering
A study with cultured macrophages demonstrated the cholesterol lowering and atherosclerosis inhibiting properties of nobiletin. Nobiletin also inhibits the formation of macrophage foam cells, macrophages loaded wit lipids, which build up on artery walls.

Memory loss
One study on a mice model showed that nobiletin my help to improve memory loss. The brains of the mice were chirurgically altered to obtain models of Alzheimer disease. It is not known if nobiletin improves the condition of human Alzheimer patients.
Acne treatment
We found one study showing that nobiletin inhibited sebum production on hamsters and inhibited the proliferation of sebocytes, the cells that form the sebaceous gland. This observation led the researchers to conclude that nobiletin could be used as a drug for acne treatment.

Synonyms
3',4',5,6,7,8-hexamethoxyflavone

Proanthocyanidins

Description
Proanthocyanidins are oligomeric flavonoids, mainly found in grapes. They are dimers (see picture) or oligomers of catechin and epicatechin and their gallic acid esters.

Distribution
Proanthocyanidins are mainly found in the skin and seeds of grapes. They are also present in red wine. During the production of red wine, the juice is left to ferment with the seeds and skins during a few days. During this fermentation process, the formed alcohol will extract the proanthocyanidins from the seeds and skins. Other rich sources are cocoa, apples, peanuts, almonds, cranberries, blueberries and bark of the maritime pine.

Properties
Consumption of red wine, red grape juice, grape skin and grape seeds has been linked to many health benefits. There are mainly two grape phytochemicals responsible for these benefits: proanthocyanidins and resveratrol. Proanthocyanidins are in the first place very strong antioxidants. Studies have shown that proanthocyanidins act as anti-cancer and anti-allergic agents, and that they improve heart health.
Antioxidant
Proanthocyanidins protect against oxidative damage and could reduce the damage caused by tobacco smoking, pollution and free radical form in our body during normal metabolism.

Hearth Disease
Many studies have shown that proanthocyanidins help to prevent the oxidation of LDL cholesterol, reduce blood pressure and improve fat metabolism. The inhibitory action against LDL cholesterol appears to increase with the degree of polymerization of the proanthocyanidin molecules. Proanthocyanidins may prevent cardiovascular disease by reducing the risk associated with high blood cholesterol. Tests with rabbits showed that an extract of grape seed proanthocyanidins significantly reduced the development of aortic atherosclerosis. Grape seed proanthocyanidins have a cardioprotective effect and protect the heart against myocardial injuries induced by isoproterenol, a drug used as an inhaled aerosol to treat asthma.

Anti-Cancer
Studies have shown that proanthocyanidins have anti-cancer and anti-tumour activity. The study by entitled Grape Seed Proanthocyanidins Induce Apoptosis and Inhibit Metastasis of Highly Metastatic Breast Carcinoma Cells (Carcinogenesis. 2006 August) concluded that grape seed proanthocyanidins may possess chemotherapeutic activity against breast cancer.
Anti-Allergic Proanthocyanidins inhibit enzymes that produce histamine and help to ease of allergies.

Facts about Proanthocyanidins
Many plants produce proanthocyanidins in their fruits, bark, leaves and seeds to protect them from predation. Proanthocyanidins give the typical astringency to foods such as wine and teas.

Research Reviews
Protective Effect of Grape Seed Polyphenols against High Glucose-Induced Oxidative Stress.

Abstracts
Proanthocyanidins as Antioxidant
Anticancer Activity of Proanthocyanidins
Effect of Procyanidins on Anticancer Drug Doxorubicin
Synonyms
Pycnogenol, OPC, Oligomeric Procyanidins

Tangeretin

Description
Tangeretin is a citrus flavonoids. It has the typical flavonoid structure and contains 5 methoxyl groups. This high level of methoxylation increases the hydrophobic character of tangeretin. It has a very bitter taste.

Distribution
Tangeretin can be found in the peel (albedo) of most citrus fruits. The whole orange fruit can contain up to 30 ppm tangeretin, but also orange juice contains some quantity. Commercial tangeretin is extracted from citrus peels.

Properties
Only recently have scientists studied the biological activity of tangeretin. They found that tangeretin is readily absorbed in tissues and that it has many beneficial properties such lowering of cholesterol, anti-tumor activity and neuroprotective action.

Cholesterol lowering
Animal studies have indicated that tangeretin has cholesterol lowering properties. One such found that rats fed with a diet containing tangeretin showed a significantly reduced (up to 40%) serum levels of LDL cholesterol.

Anti-tumor
In-vitro test have shown that tangeretin acts as an antitumor agent. It induced apoptosis in leukemia cells without being toxic to normal cells. Tangeretin stops the growth of cancer cell in the G1 phase. On the other hand, tangeretin seems to counteract the anticancer drug tamoxifen and to suppress the activity of natural killer cells.

Neuroprotection
A study with a rat model of Parkinson's disease showed that tangeretin increased the levels of dopamine and has potential neuroprotective activity.

Synonyms
5,6,7,8-tetramethoxy-2-(4-methoxyphenyl)-4H-1-benzopyran-4-one 5,6,7,8,4'-pentamethoxyflavone



Sumber: http://www.phytochemicals.info/phytochemicals/flavonoids.php

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