''THERE IS IN THE WORLD NO SUBSTANCE THAT MAY NOT BE USED AS MEDICINE IN THIS OR THAT MANNER, FOR THIS OR THAT PURPOSE".-CHARAKA
जगत्येवं अनोउषधं नाति जगति किञ्जित
ANTI OXIDANTS AND AYURVEDA.
An antioxidant is a molecule that inhibits the oxidation of other molecules.Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When the chain reaction occurs in a cell, it can cause damage or death to the cell. Antioxidants terminate these chain reactions by removing free radical intermediates, and inhibit other oxidation reactions. They do this by being oxidized themselves, so antioxidants are often reducing agents such as thiols, ascorbic acid, or polyphenols.
Although oxidation reactions are crucial for life, they can also be damaging; plants and animals maintain complex systems of multiple types of antioxidants, such as glutathione, vitamin C, vitamin A, and vitamin E as well as enzymes such as catalase, superoxide dismutase and various peroxidases. Insufficient levels of antioxidants, or inhibition of the antioxidant enzymes, cause oxidative stressand may damage or kill cells. Oxidative stress is damage to cell structure and cell function by overly reactive oxygen-containing molecules and chronic excessive inflammation. Oxidative stress seems to play a significant role in many human diseases, including cancers. The use of antioxidants in pharmacology is intensively studied, particularly as treatments for stroke and neurodegenerative diseases. For these reasons, oxidative stress can be considered to be both the cause and the consequence of some diseases.
Antioxidants are widely used in dietary supplements and have been investigated for the prevention of diseases such as cancer,coronary heart disease and even altitude sickness. Although initial studies suggested that antioxidant supplements might promote health, later large clinical trials with a limited number of antioxidants detected no benefit and even suggested that excess supplementation with certain putative antioxidants may be harmful.Antioxidants also have many industrial uses, such aspreservatives in food and cosmetics and to prevent the degradation of rubber and gasoline.
History
As part of their adaptation from marine life, terrestrial plants began producing non-marine antioxidants such as ascorbic acid (Vitamin C), polyphenols and tocopherols. The evolution of angiosperm plants between 50 and 200 million years ago resulted in the development of many antioxidant pigments – particularly during the Jurassic period – as chemical defences against reactive oxygen species that are byproducts of photosynthesis. Originally, the term antioxidant specifically referred to a chemical that prevented the consumption of oxygen. In the late 19th and early 20th centuries, extensive study concentrated on the use of antioxidants in important industrial processes, such as the prevention of metal corrosion, the vulcanization of rubber, and the polymerization of fuels in the fouling of internal combustion engines.
Early research on the role of antioxidants in biology focused on their use in preventing the oxidation of unsaturated fats, which is the cause of rancidity. Antioxidant activity could be measured simply by placing the fat in a closed container with oxygen and measuring the rate of oxygen consumption. However, it was the identification of vitamins A, C, and Eas antioxidants that revolutionized the field and led to the realization of the importance of antioxidants in the biochemistry of living organisms. The possible mechanisms of action of antioxidants were first explored when it was recognized that a substance with anti-oxidative activity is likely to be one that is itself readily oxidized. Research into how vitamin E prevents the process of lipid peroxidation led to the identification of antioxidants as reducing agents that prevent oxidative reactions, often by scavenging reactive oxygen species before they can damage cells.
Oxidative challenge in biology
A paradox in metabolism is that, while the vast majority of complex life on Earth requires oxygen for its existence, oxygen is a highly reactive molecule that damages living organisms by producing reactive oxygen species. Consequently, organisms contain a complex network of antioxidant metabolites and enzymes that work together to prevent oxidative damage to cellular components such as DNA, proteins andlipids. In general, antioxidant systems either prevent these reactive species from being formed, or remove them before they can damage vital components of the cell. However, reactive oxygen species also have useful cellular functions, such as redox signaling. Thus, the function of antioxidant systems is not to remove oxidants entirely, but instead to keep them at an optimum level.
Metabolites
Overview
Antioxidants are classified into two broad divisions, depending on whether they are soluble in water (hydrophilic) or in lipids (lipophilic). In general, water-soluble antioxidants react with oxidants in the cell cytosol and the blood plasma, while lipid-soluble antioxidants protect cell membranes from lipid peroxidation.These compounds may be synthesized in the body or obtained from the diet. The different antioxidants are present at a wide range of concentrations in body fluids and tissues, with some such as glutathione orubiquinone mostly present within cells, while others such as uric acid are more evenly distributed (see table below). Some antioxidants are only found in a few organisms and these compounds can be important in pathogens and can be virulence factors.
The relative importance and interactions between these different antioxidants is a very complex question, with the various metabolites and enzyme systems having synergistic and interdependent effects on one another. The action of one antioxidant may therefore depend on the proper function of other members of the antioxidant system. The amount of protection provided by any one antioxidant will also depend on its concentration, its reactivity towards the particular reactive oxygen species being considered, and the status of the antioxidants with which it interacts.
Oxidative stress in disease
Oxidative stress is thought to contribute to the development of a wide range of diseases including Alzheimer's disease, Parkinson's disease, the pathologies caused by diabetes, rheumatoid arthritis, and neurodegeneration in motor neuron diseases. In many of these cases, it is unclear if oxidants trigger the disease, or if they are produced as a secondary consequence of the disease and from general tissue damage; One case in which this link is particularly well-understood is the role of oxidative stress in cardiovascular disease. Here, low density lipoprotein (LDL) oxidation appears to trigger the process of atherogenesis, which results in atherosclerosis, and finally cardiovascular disease.
Oxidative damage in DNA can cause cancer. Several antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione S-transferase etc. protect DNA from oxidative stress. It has been proposed that polymorphisms in these enzymes are associated with DNA damage and subsequently the individual's risk of cancer susceptibility.
A low calorie diet extends median and maximum lifespan in many animals. This effect may involve a reduction in oxidative stress. While there is some evidence to support the role of oxidative stress in aging in model organisms such as Drosophila melanogaster and Caenorhabditis elegans, the evidence in mammals is less clear.Indeed, a 2009 review of experiments in mice concluded that almost all manipulations of antioxidant systems had no effect on aging. Diets high in fruit and vegetables, which are high in antioxidants, promote health and reduce the effects of aging; antioxidant vitamin supplementation has no detectable effect on the aging process, so the effects of fruit and vegetables may be unrelated to their antioxidant contents. One reason for this might be the fact that consuming antioxidant molecules such as polyphenols and vitamin E will produce changes in other parts of metabolism, and it may be these other effects that are the real reason these compounds are important in human nutrition.
Potential health effects
Organ function
The brain is uniquely vulnerable to oxidative injury, due to its high metabolic rate and elevated levels of polyunsaturated lipids, the target of lipid peroxidation. Consequently, antioxidants are commonly used as medications to treat various forms of brain injury. Here, superoxide dismutase mimetics,sodium thiopental and propofol are used to treatreperfusion injury and traumatic brain injury, while the experimental drugs disufenton sodium and ebselen are being applied in the treatment of stroke. These compounds appear to prevent oxidative stress in neurons and prevent apoptosis and neurological damage. Antioxidants are also being investigated as possible treatments for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, and as a way to prevent noise-induced hearing loss. Targeted antioxidants may lead to better medicinal effects. Mitochondria-targeted ubiquinone, for example, may prevent damage to the liver caused by excessive alcohol.
Physical exercise
During exercise, oxygen consumption can increase by a factor of more than 10. This leads to a large increase in the production of oxidants and results in damage that contributes to muscular fatigue during and after exercise. The inflammatory response that occurs after strenuous exercise is also associated with oxidative stress, especially in the 24 hours after an exercise session. The immune system response to the damage done by exercise peaks 2 to 7 days after exercise, which is the period during which most of the adaptation that leads to greater fitness occurs. During this process, free radicals are produced by neutrophils to remove damaged tissue. As a result, excessive antioxidant levels may inhibit recovery and adaptation mechanisms. Antioxidant supplements may also prevent any of the health gains that normally come from exercise, such as increasedinsulin sensitivity.
The evidence for benefits from antioxidant supplementation in vigorous exercise is mixed. There is strong evidence that one of the adaptations resulting from exercise is a strengthening of the body's antioxidant defenses, particularly the glutathione system, to regulate the increased oxidative stress. This effect may be to some extent protective against diseases which are associated with oxidative stress, which would provide a partial explanation for the lower incidence of major diseases and better health of those who undertake regular exercise.
No benefits for physical performance to athletes are seen with vitamin E supplementation. Indeed, despite its key role in preventing lipid membrane peroxidation, 6 weeks of vitamin E supplementation had no effect on muscle damage in ultramarathon runners. Although there appears to be no increased requirement for vitamin C in athletes, there is some evidence that vitamin C supplementation increased the amount of intense exercise that can be done and vitamin C supplementation before strenuous exercise may reduce the amount of muscle damage. Other studies found no such effects, and some research suggests that supplementation with amounts as high as 1000 mg inhibits recovery.
A review published in Sports Medicine looked at 150 studies on antioxidant supplementation during exercise. The review found that even studies that found a reduction in oxidative stress failed to demonstrate benefits to performance or prevention of muscle damage. Some studies indicated that antioxidant supplementation could work against the cardiovascular benefits of exercise.
AYURVEDIC HERBS AS ANTI-OXIDANTS
EMBELLICA OFFICIONALIS-prevent radical formation mainly by enhancing the levels of superoxide dismutases and catalase, or by sequestering metals like iron. Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation. Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.
HEMIDESMUS INDICUS-prevent radical formation mainly by enhancing the levels of superoxide dismutases and catalase, or by sequestering metals like iron. Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation.
OCIMIUM SANCTUM--prevent radical formation mainly by enhancing the levels of superoxide dismutases and catalase, or by sequestering metals like iron. Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation. Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.Scavenging of primary radicals OH, O2 or by breaking of chain reaction. Repair of DNA & other cellular constituents.
PICORRIZHA KURRORA-prevent radical formation mainly by enhancing the levels of superoxide dismutases and catalase, or by sequestering metals like iron. Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation.
TINOSPORA CORDIFOLIA-prevent radical formation mainly by enhancing the levels of superoxide dismutases and catalase, or by sequestering metals like iron. Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation. Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.
WITHANIA SOMNIFERA-prevent radical formation mainly by enhancing the levels of superoxide dismutases and catalase, or by sequestering metals like iron.. Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.
ZINZIBER OFFICIONALES-prevent radical formation mainly by enhancing the levels of superoxide dismutases and catalase, or by sequestering metals like iron.. Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.
ALOE VERA-prevent radical formation mainly by enhancing the levels of superoxide dismutases and catalase, or by sequestering metals like iron. Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation. Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.
CURCUMA LONGA-.Scavenging of primary radicals OH, O2 or by breaking of chain reaction. Repair of DNA & other cellular constituents.Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation. Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.
ALLIUM SATIVUM-.Scavenging of primary radicals OH, O2 or by breaking of chain reaction. Repair of DNA & other cellular constituents.Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation. Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.
ALLIUM CEPA-.Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation.
ASPARAGUS RACEMOSUS-Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation.
AZDIRACHTA INDICA--Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation.
GLYCERRIZHA GLABRA-Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation.
MANGIFERA INDICA-Scavenging of secondary radical or breaking of chain propogation, conventionally studied as inhibition of lipid peroxidation.
CAMELIA SINENSIS- Repair and reconstruction of lipid membrane aided by glutathione peroxidases or by increase in level of glutathione.
CLINICALLY PROVEN IMMUNOMODULATORY AYURVEDIC DRUGS
WITHANIA SOMNIFERA
CLITORIS TERNEATA
TERMINALIA BETERICA
BERBERIS ARISTATA
TINOSPARA CORDIFOLIA
CURCUMA LONGA
ARISTOLOCHIA INDICA
NARDOSTACHYS JATAMANSI
ANDROGRAPHIS PANICULATA
PICORRIZHA KURRORA
ALOE VER
ALLIUM SATIVUM
AZADIRACHTA INDICA
ASPARAGUS RACEMOSUS
ALBIZZIA LEBBEK
MECHANISM BASED SCREENING
Molecular pharmacology provides a new interface between Ayurveda and modern medicine. Based on experiential wisdom, charaka, sushrutha and vagbhat described 700 herbal drugs with their properties and clinical effects. Based on clinical effects they described 50 categories of drugs such as appetisers, digestive stimulants, laxatives, anti-diarhhea, anti-emetic, anti-haemorrhoid, anti-inflammatory, anti-puritic, anti-asthmatic, anti-epileptic, anti-helminthic, haemopoeitic, haemostatic, analgesic, sedative, promoters of life, promoters of strength, complexion, voice, semen and sperm, breast milk secretion, fracture and wound healing, destroyers of kidney stones etc. Based on our current knowledge of molecular pharmacology we can attempt the characterization of Ayurvedic drugs at the molecular level. One example illustrates this approach. Reserpine acts by blocking pre synaptic neuronal vesicular reuptake and storage of mono amines-nor epinephrine, dopamine & serotonin.
Today there is a world wide search for biologically active molecules of plant origin. Many renowned multinational drug houses have launched very active programmes of mechanism based natural product discovery research. It is my belief that subjecting Ayurvedic herbal drugs to mechanism based screening will be far more rewarding because their choice has already been backed by experiential wisdom. The 40 single herbs described by vagbhat should be studied with mechanisms-based screening for their anti-oxidant, anti-inflammatory actions as well eability to decrease advanced glycosylation end products.
There is seemingly an infinite list of o;d and new molecules which interacts with an ever expanding array of cellular targets. As Charak said : ''THERE IS IN THE WORLD NO SUBSTANCE THAT MAY NOT BE USED AS MEDICINE IN THIS OR THAT MANNER, FOR THIS OR THAT PURPOSE".In todays era molecular medicine, disease is dissonance-due to excessive interaction, absent interaction or erroneous interaction between signaling molecules and their receptors. This concept is beautifully described by Ayurveda in three words-
ATIYOGA-excessive interaction
AYOGA-absent interaction
MITHYAYOGA-erroneous interaction
CHEMOPREVENTION OF CANCER
Chemoprevention of cancer is a relatively new concept. It involves the use of specific natural or synthetic chemical agents to reverse, supress or prevent carcinogenesis before the development of invasive malignancy.Many Ayurvedic herbal drugs with anti-oxidant and immuno-stimulant properties are ideal candidates for chemoprevention of cancer. This hypothesis should be tested by a planned randomised placebo-controlled clinical trial on a large population.
VATA, PITTA, KAPHA AND SIGNAL TRANSDUCTION
A look at the table on receptors and signal transduction will show that although the signalling molecules are diverse, the signal transduction mechanisms are limited viz.
1.Increase or decrease in cAMP or cGMP
2.Increase or decrease in IP3 /DAG
3.Increase or decrease in Ca2+ and other ion channels
Conceptually one can see a close similarity of this with the Ayrvedic concept of Vata vruddhi or Vata shaman, Pitta vruddhi or Pitta shaman, Kapha vruddhi or kapha shaman either individually or in combination.
Although there can be no one-to-one parallel between the 2 vocabularies the modern Vaidya may think of assimilating all the 20th century knowledge of molecular biology to expand his old concepts which are also derived from molecular biology. This is what the spirit of Charak, Sushruth, and Vaghbat would expect of him.
FROM AYURVEDA AND MODERN MEDICINE , DR.R.D.LELE.
WIKIPEDIA
