Free radicals or Reactive Oxygen Species (ROS)

It is ironic that oxygen, an element indispensable for life can, under certain situations, have severely deleterious effects on the human body. Most of the potentially harmful effects of oxygen are due to the formation and activity of a number of chemical compounds, known as reactive oxygen species, which have a tendency to donate oxygen to other substances. Many such reactive species are free radicals and have a surplus of one or more free-floating electrons rather than having matched pairs and are, therefore, unstable and highly reactive. Types of free radicals include the hydroxyl radical (OH.), the superoxide radical (O.2), and the lipid peroxyl radical (LOO.).Production of free radicals in the human body Free radicals and other reactive oxygen species are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants and industrial chemicals. Free radical formation occurs continuously in the cells as a consequence of both enzymatic and non-enzymatic reactions . Enzymatic reactions which serve as sources of free radicals include those involved in the respiratory chain, in phagocytosis, in prostaglandin synthesis and in the cytochrome P450 system. Free radicals also arise in non-enzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing radiations. Some internally generated sources of free radicals are
· Mitochondria
· Phagocytes
· Xanthine oxidase
· Reactions involving iron and other transition metals
· Arachidonate pathways
· Peroxisomes
· Exercise
· Inflammation
· Ischaemia/reperfusion.

Some externally generated sources of free radicals are
· Cigarette smoke
· Environmental pollutants
· Radiation
· Ultraviolet light
· Certain drugs, pesticides, anaesthetics and industrial solvents
· Ozone.

With electrons unhinged, free radicals roam the body, wreaking havoc. The free radical, in an effort to achieve stability, attacks nearby molecules to obtain another electron and, in doing so, damages those molecules. If free radicals are not inactivated, their chemical reactivity can damage all cellular macromolecules including proteins, carbohydrates, lipids and nucleic acids. Their destructive effects on proteins may play a role in the causation of cataracts. Free radical damage to DNA is also implicated in the causation of cancer and its effect on LDL cholesterol is very likely responsible for heart disease. In fact, the theory associating free radicals with the aging process has also gained widespread acceptance .

The free radical diseases
A well accepted fact is the increasing incidence of disease with advancing age. A plausible explanation for the association of age and disease is based on the implication of free radical reactions in the pathogenesis of several disorders. Free radical reactions are expected to produce progressive adverse changes that accumulate with age throughout the body. Such “normal” changes with age are relatively common to all. However, superimposed on this common pattern are patterns influenced by genetics and environmental differences that modulate free radical damage. These are manifested as diseases at certain ages determined by genetic and environmental factors. Cancer and atherosclerosis, two major causes of death, are salient “free radical” diseases. Cancer initiation and promotion is associated with chromosomal defects and oncogene activation. It is possible that endogenous free radical reactions, like those initiated by ionizing radiation, may result in tumor formation. The highly significant correlation between consumption of fats and oils and death rates from leukemia and malignant neoplasia of the breast, ovaries and rectum among persons over 55 years may be a reflection of greater lipid peroxidation . Studies on atherosclerosis reveal the probability that the disease may be due to free radical reactions involving diet-derived lipids in the arterial wall and serum to yield peroxides and other substances. These compounds induce endothelial cell injury and produce changes in the arterial walls.

Antioxidants neutralizes the free radical damage
The human body has several mechanisms to counteract damage by free radicals and other reactive oxygen species. These act on different oxidants as well as in different cellular compartments. One important line of defence is a system of enzymes, including glutathione peroxidases, superoxide dismutases and catalase, which decrease concentrations of the most harmful oxidants in the tissues. Several essential minerals including selenium, copper, manganese and zinc are necessary for the formation or activity of these enzymes. Hence, if the nutritional supply of these minerals is inadequate, enzymatic defences against free radicals may be impaired.

The second line of defence against free radical damage is the presence of antioxidants. An antioxidant is a molecule stable enough to donate an electron to a rampaging free radical and neutralize it, thus reducing its capacity to damage. Some such antioxidants, including glutathione, ubiquinol and uric acid, are produced during normal metabolism in the body. Other lighter antioxidants are found in the diet. Although about 4000 antioxidants have been identified, the best known are vitamin E, vitamin C and the carotenoids. Many other non-nutrient food substances, generally phenolic or polyphenolic compounds, display antioxidant properties and, thus, may be important for health.

Although a wide variety of antioxidants in foods contribute to disease prevention, the bulk of research has focused on three antioxidants which are essential nutrients or precursors of nutrients. These are vitamin E, vitamin C and the carotenoids. Each of these antioxidant nutrients have specific activities and they often work synergistically to enhance the overall antioxidant capability of the body.

The balance between the production of free radicals and the antioxidant defences in the body has important health implications. If there are too many free radicals produced and too few antioxidants, a condition of “oxidative stress” develops which may cause chronic damage. As mentioned above, free radicals have been implicated in several health problems. Cancer, atherosclerosis, cerebrovascular accidents, myocardial infarction, senile cataracts, acute respiratory distress syndrome and rheumatoid arthritis are just a few examples. Numerous studies have shown the protective effects of antioxidant nutrients on these health problems.
Antioxidant property of Noni

Endogenous antioxidants and role of Noni – Our body has evolved with endogenous defense mechanisms to protect against free radical induced cell damage. Glutathione peroxidase, catalase, and Superoxide dismutases are three primary antioxidant enzymes in our body, which involved in direct elimination of free radicals or reactive oxygen species from our body. They require micronutrient such as selenium, iron, copper, zinc, and manganese as cofactors for their formation and optimum catalytic and effective antioxidant activity. Noni contain all the trace minerals that help for optimum catalytic activity of those three important antioxidant enzymes for an effective antioxidant defense mechanism.

Glutathione, ascorbic acid, alpha-tocopherol, beta-carotene, bilirubin, selenium, dihydrolipoic acid, reduced CoQ10, melatonin, uric acid etc., as a whole play a homoeostatic or protective role against ROS produced during normal cellular metabolism and after active oxidation insult. Noni contains all the above phyto chemicals and vitamins in abundant quantity. Glutathione (GSH) is the most significant component which directly quenches Reactive Oxygen Species (ROS) such as lipid peroxides and plays major role in xenobiotic metabolism. Glutathione is a tripeptide made up of the amino acids gamma-glutamic acid, cysteine, and glycine. Noni contain all those glutathione making amino acids in abundant number. Thus Noni increases the body’s glutathione level. Noni stimulates more melatonin secretion from the pineal body. It also maintains ascorbate (vitamin C) and alpha-tocopherol (vitamin E), in their reduced form, which also exert an antioxidant effect by quenching free radicals.

Exogenous antioxidants: Contribution from Noni

A number of other dietary antioxidants known as phytonutrients or phytochemicals that are being increasingly appreciated for their antioxidant activity. One example is flavonoids which are a group of polyphenolic compounds. They are responsible for the different brilliant colors such as blue, scarlet, and orange. Noni contain 150 above phytochemicals including all flavonoids. Flavonoids exhibit several biological effects such as antitumoural, anti-ischaemic, anti-allergic, anti-hepatotoxic, anti-ulcerative, and anti inflammatory activities. These are also known to inhibit the activities of several bad enzymes like lipoxygenase, cyclooxygenase, monooxygenase, xanthine oxidase, glutathione-S transferase, mitochondrial succino-oxidase, and protein kinases. Many of the biological activities of flavonoids are attributed to their antioxidant properties and free radical scavenging capabilities. Noni is rich with many flavonoids.

It is ironic that oxygen, an element indispensable for life can, under certain situations, have severely deleterious effects on the human body. Most of the potentially harmful effects of oxygen are due to the formation and activity of a number of chemical compounds, known as reactive oxygen species, which have a tendency to donate oxygen to other substances. Many such reactive species are free radicals and have a surplus of one or more free-floating electrons rather than having matched pairs and are, therefore, unstable and highly reactive. Types of free radicals include the hydroxyl radical (OH.), the superoxide radical (O.2), and the lipid peroxyl radical (LOO.).

Production of free radicals in the human body Free radicals and other reactive oxygen species are derived either from normal essential metabolic processes in the human body or from external sources such as exposure to X-rays, ozone, cigarette smoking, air pollutants and industrial chemicals. Free radical formation occurs continuously in the cells as a consequence of both enzymatic and non-enzymatic reactions . Enzymatic reactions which serve as sources of free radicals include those involved in the respiratory chain, in phagocytosis, in prostaglandin synthesis and in the cytochrome P450 system. Free radicals also arise in non-enzymatic reactions of oxygen with organic compounds as well as those initiated by ionizing radiations. Some internally generated sources of free radicals are
· Mitochondria
· Phagocytes
· Xanthine oxidase
· Reactions involving iron and other transition metals
· Arachidonate pathways
· Peroxisomes
· Exercise
· Inflammation
· Ischaemia/reperfusion.

Some externally generated sources of free radicals are
· Cigarette smoke
· Environmental pollutants
· Radiation
· Ultraviolet light
· Certain drugs, pesticides, anaesthetics and industrial solvents
· Ozone.

With electrons unhinged, free radicals roam the body, wreaking havoc. The free radical, in an effort to achieve stability, attacks nearby molecules to obtain another electron and, in doing so, damages those molecules. If free radicals are not inactivated, their chemical reactivity can damage all cellular macromolecules including proteins, carbohydrates, lipids and nucleic acids. Their destructive effects on proteins may play a role in the causation of cataracts. Free radical damage to DNA is also implicated in the causation of cancer and its effect on LDL cholesterol is very likely responsible for heart disease. In fact, the theory associating free radicals with the aging process has also gained widespread acceptance .

The free radical diseases
A well accepted fact is the increasing incidence of disease with advancing age. A plausible explanation for the association of age and disease is based on the implication of free radical reactions in the pathogenesis of several disorders. Free radical reactions are expected to produce progressive adverse changes that accumulate with age throughout the body. Such “normal” changes with age are relatively common to all. However, superimposed on this common pattern are patterns influenced by genetics and environmental differences that modulate free radical damage. These are manifested as diseases at certain ages determined by genetic and environmental factors. Cancer and atherosclerosis, two major causes of death, are salient “free radical” diseases. Cancer initiation and promotion is associated with chromosomal defects and oncogene activation. It is possible that endogenous free radical reactions, like those initiated by ionizing radiation, may result in tumor formation. The highly significant correlation between consumption of fats and oils and death rates from leukemia and malignant neoplasia of the breast, ovaries and rectum among persons over 55 years may be a reflection of greater lipid peroxidation . Studies on atherosclerosis reveal the probability that the disease may be due to free radical reactions involving diet-derived lipids in the arterial wall and serum to yield peroxides and other substances. These compounds induce endothelial cell injury and produce changes in the arterial walls.

Antioxidants neutralizes the free radical damage
The human body has several mechanisms to counteract damage by free radicals and other reactive oxygen species. These act on different oxidants as well as in different cellular compartments. One important line of defence is a system of enzymes, including glutathione peroxidases, superoxide dismutases and catalase, which decrease concentrations of the most harmful oxidants in the tissues. Several essential minerals including selenium, copper, manganese and zinc are necessary for the formation or activity of these enzymes. Hence, if the nutritional supply of these minerals is inadequate, enzymatic defences against free radicals may be impaired.

The second line of defence against free radical damage is the presence of antioxidants. An antioxidant is a molecule stable enough to donate an electron to a rampaging free radical and neutralize it, thus reducing its capacity to damage. Some such antioxidants, including glutathione, ubiquinol and uric acid, are produced during normal metabolism in the body. Other lighter antioxidants are found in the diet. Although about 4000 antioxidants have been identified, the best known are vitamin E, vitamin C and the carotenoids. Many other non-nutrient food substances, generally phenolic or polyphenolic compounds, display antioxidant properties and, thus, may be important for health.

Although a wide variety of antioxidants in foods contribute to disease prevention, the bulk of research has focused on three antioxidants which are essential nutrients or precursors of nutrients. These are vitamin E, vitamin C and the carotenoids. Each of these antioxidant nutrients have specific activities and they often work synergistically to enhance the overall antioxidant capability of the body.

The balance between the production of free radicals and the antioxidant defences in the body has important health implications. If there are too many free radicals produced and too few antioxidants, a condition of “oxidative stress” develops which may cause chronic damage. As mentioned above, free radicals have been implicated in several health problems. Cancer, atherosclerosis, cerebrovascular accidents, myocardial infarction, senile cataracts, acute respiratory distress syndrome and rheumatoid arthritis are just a few examples. Numerous studies have shown the protective effects of antioxidant nutrients on these health problems.
Antioxidant property of Noni

Endogenous antioxidants and role of Noni – Our body has evolved with endogenous defense mechanisms to protect against free radical induced cell damage. Glutathione peroxidase, catalase, and Superoxide dismutases are three primary antioxidant enzymes in our body, which involved in direct elimination of free radicals or reactive oxygen species from our body. They require micronutrient such as selenium, iron, copper, zinc, and manganese as cofactors for their formation and optimum catalytic and effective antioxidant activity. Noni contain all the trace minerals that help for optimum catalytic activity of those three important antioxidant enzymes for an effective antioxidant defense mechanism.

Glutathione, ascorbic acid, alpha-tocopherol, beta-carotene, bilirubin, selenium, dihydrolipoic acid, reduced CoQ10, melatonin, uric acid etc., as a whole play a homoeostatic or protective role against ROS produced during normal cellular metabolism and after active oxidation insult. Noni contains all the above phyto chemicals and vitamins in abundant quantity. Glutathione (GSH) is the most significant component which directly quenches Reactive Oxygen Species (ROS) such as lipid peroxides and plays major role in xenobiotic metabolism. Glutathione is a tripeptide made up of the amino acids gamma-glutamic acid, cysteine, and glycine. Noni contain all those glutathione making amino acids in abundant number. Thus Noni increases the body’s glutathione level. Noni stimulates more melatonin secretion from the pineal body. It also maintains ascorbate (vitamin C) and alpha-tocopherol (vitamin E), in their reduced form, which also exert an antioxidant effect by quenching free radicals.

Exogenous antioxidants: Contribution from Noni

A number of other dietary antioxidants known as phytonutrients or phytochemicals that are being increasingly appreciated for their antioxidant activity. One example is flavonoids which are a group of polyphenolic compounds. They are responsible for the different brilliant colors such as blue, scarlet, and orange. Noni contain 150 above phytochemicals including all flavonoids. Flavonoids exhibit several biological effects such as antitumoural, anti-ischaemic, anti-allergic, anti-hepatotoxic, anti-ulcerative, and anti inflammatory activities. These are also known to inhibit the activities of several bad enzymes like lipoxygenase, cyclooxygenase, monooxygenase, xanthine oxidase, glutathione-S transferase, mitochondrial succino-oxidase, and protein kinases. Many of the biological activities of flavonoids are attributed to their antioxidant properties and free radical scavenging capabilities. Noni is rich with many flavonoids.

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