T.P.A. Devasagayam

Indian Herbs and Herbal Drugs Used for the Treatment of Diabetes

Traditional Medicines derived from medicinal plants are used by about 60% of the world’s population. This review focuses on Indian Herbal drugs and plants used in the treatment of diabetes, especially in India. Diabetes is an important human ailment afflicting many from various walks of life in different countries. In India it is proving to be a major health problem, especially in the urban areas. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, herbal formulations are preferred due to lesser side effects and low cost. A list of medicinal plants with proven antidiabetic and related beneficial effects and of herbal drugs used in treatment of diabetes is compiled. These include, Allium sativum, Eugenia jambolana, Momordica charantia Ocimum sanctum, Phyllanthus amarus, Pterocarpus marsupium, Tinospora cordifolia, Trigonella foenum graecum and Withania somnifera. One of the etiologic factors implicated in the development of diabetes and its complications is the damage induced by free radicals and hence an antidiabetic compound with antioxidant properties would be more beneficial. Therefore information on antioxidant effects of these medicinal plants is also included.

Decreased lipid peroxidation in the rat kidney during gestation

Renal malonaldehyde content and lipid peroxidation, induced by ascorbate, NADPH and cumene hydroperoxide, are significantly decreased during gestation in rats. Lipid peroxidation tends to reach normal levels in the kidney post partum. In the renal mitochondria lipid peroxidation without co-factors and that induced by cumene hydroperoxide, ascorbate and NADPH is decreased during pregnancy. However, in the microsomes, only lipid peroxidation induced by NADPH and cumene hydroperoxide is affected. The observed decrease in lipid peroxidation during gestation is reflected by low levels of total lipid and phospholipid. Endogenous inhibitors of lipid peroxidation also increase during pregnancy.

Caffeine as an antioxidant: inhibition of lipid peroxidation induced by reactive oxygen species

Caffeine (1,3,7-trimethyl xanthine), an ingredient of coffee, has been investigated for its potential antioxidant activity against oxidative damage to rat liver microsomes. Such damage was induced by three reactive oxygen species of cardinal importance in causing membrane damage in vivo namely hydroxyl radical (.OH), peroxyl radical (ROO.) and singlet oxygen (1O2). The results obtained showed that caffeine was an effective inhibitor of lipid peroxidation, at millimolar concentrations, against all the three reactive species. The extent of inhibition was high against peroxidation induced by .OH, medium against 1O2 and low against ROO. In general, the antioxidant ability of caffeine was similar to that of the established biological antioxidant glutathione and significantly higher than ascorbic acid. Investigations into the possible mechanisms involved in the observed antioxidant effect reveal that the quenching of these reactive species by caffeine may be one of the possible factor responsible. The rate constant of caffeine with .OH was 7.3 x 10(9) M-1 s-1 and with 1O2 it was 2.9 x 10(7) M-1 s-1. Considering their potential for damage, half-life estimates and generation in biological systems, the ability of caffeine to inhibit oxidative damage induced by these reactive species in membranes suggest one more positive attribute of caffeine, whose daily intake as coffee may be considerable in most populations.

Reactive oxygen species mediated membrane damage induced by fullerene derivatives and its possible biological implications.

Fullerenes have attracted considerable attention in recent years due to their unique chemical structure and potential applications. Hence it is of interest to study their biological effects. Using rat liver microsomes as model systems we have examined the ability of the most commonly used fullerene, C60 and its water-soluble derivative, C60(OH)18 to induce membrane damage on photosensitization. For photoexcitation, UV or tungsten lamps were used. Damage was assessed as lipid peroxidation products like conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS). protein oxidation in the form of protein carbonyls, besides loss of membrane bound enzymes. Both fullerene derivatives induced significant oxidative damage. The alterations induced were both time- and concentration-dependent. Role of different reactive oxygen species (ROS) in the damage induced was examined by various scavengers of ROS and by deuteration of the buffer. The changes induced by C60 were predominantly due to 1O2 while that by C60(OH)18 was mainly due to radical species. Biological antioxidants such as glutathione, ascorbic acid and alpha-tocopherol were capable of inhibiting membrane damage induced by both the fullerenes. However, the damage induced by C60(OH)18 was more for both lipids and proteins than that showed by C60. C60 also showed enhancement in the formation of lipid peroxidation in sarcoma 180 ascites microsomes. In conclusion, our studies indicate that fullerene/its derivative can generate ROS on photoexcitation and can induce significant lipid peroxidation/protein oxidation in membranes and these phenomena can be prevented by endogenous/natural antioxidants.

Antioxidant properties of Asparagus racemosus against damage induced by γ-radiation in rat liver mitochondria

The possible antioxidant effects of crude extract and a purified aqueous fraction of Asparagus racemosus against membrane damage induced by the free radicals generated during gamma-radiation were examined in rat liver mitochondria. gamma-Radiation, in the dose range of 75-900 Gy, induced lipid peroxidation as assessed by the formation of thiobarbituric acid reactive substances (TBARS) and lipid hydroperoxides (LOOH). Using an effective dose of 450 Gy, antioxidant effects of A. racemosus extract were studied against oxidative damage in terms of protection against lipid peroxidation, protein oxidation, depletion of protein thiols and the levels of the antioxidant enzyme, superoxide dismutase. An active fraction consisting of polysaccharides (termed as P3) was effective even at a low concentration of 10 microg/ml. Both the crude extract as well as the P3 fraction significantly inhibited lipid peroxidation and protein oxidation. The antioxidant effect of P3 fraction was more pronounced against lipid peroxidation, as assessed by TBARS formation, while that of the crude extract was more effective in inhibiting protein oxidation. Both the crude extract and P3 fraction also partly protects against radiation-induced loss of protein thiols and inactivation of superoxide dismutase. The inhibitory effects of these active principles, at the concentration of 10 microg/ml, are comparable to that of the established antioxidants glutathione and ascorbic acid. Hence our results indicate that extracts from A. racemosus have potent antioxidant properties in vitro in mitochondrial membranes of rat liver.

Tocotrienols from palm oil as potent inhibitors of lipid peroxidation and protein oxidation in rat brain mitochondria

The tocotrienol-rich-fraction (TRF) from palm oil, being tried as a more economical and efficient substitute for alpha-tocopherol, significantly inhibited oxidative damage in vitro to both lipids and proteins in rat brain mitochondria induced by ascorbate-Fe2+, the free radical initiator azobis(2-amidopropane)dihydrochloride (AAPH) and photosensitisation. The observed inhibitory effect was both time- and concentration-dependent. At a low concentration of 5 microM, TRF can significantly inhibit oxidative damage to both lipids and proteins. The inhibitory effect of TRF seems to be mainly due to gamma-tocotrienol and to a lesser extent alpha- and delta-tocotrienols. TRF was significantly more effective than alpha-tocopherol. This fraction from palm oil can be considered a natural antioxidant supplement capable of protecting the brain against oxidative damage and thereby from the ensuing adverse alterations.

Recent Advances in Indian Herbal Drug Research Guest Editor: Thomas Paul Asir Devasagayam Current Status of Herbal Drugs in India: An Overview

Herbal drugs constitute a major share of all the officially recognised systems of health in India viz. Ayurveda, Yoga, Unani, Siddha, Homeopathy and Naturopathy, except Allopathy. More than 70% of India’s 1.1 billion population still use these non-allopathic systems of medicine. Currently, there is no separate category of herbal drugs or dietary supplements, as per the Indian Drugs Act. However, there is a vast experiential-evidence base for many of the natural drugs. This offers immense opportunities for Observational Therapeutics and Reverse Pharmacology. Evidence-based herbals are widely used in the diverse systems and manufactured, as per the pharmacopoeial guidelines, by a well-organised industry. Significant basic and clinical research has been carried out on the medicinal plants and their formulations, with the state-of-the-art methods in a number of Institutes/Universities. There are some good examples. Indian medicinal plants also provide a rich source for antioxidants that are known to prevent/delay different diseased states. The antioxidant protection is observed at different levels. The medicinal plants also contain other beneficial compounds like ingredients for functional foods. Hence, the global knowledge about Ayurveda and Indian herbals will hopefully be enhanced by information on the evidence-base of these plants. This will yield rich dividends in the coming years.

Tocotrienols from palm oil as effective inhibitors of protein oxidation and lipid peroxidation in rat liver microsomes

Tocotrienols from palm oil showed significant ability to inhibit oxidative damage induced by ascorbate-Fe2+ and photosensitization, involving different mechanisms, in rat liver microsomes. The tocotrienol-rich fraction from palm oil (TRF), being tried as a more economical and efficient substitute for α-tocopherol, showed time- and concentration-dependent inhibition of protein oxidation as well as lipid peroxidation. It was more effective against protein oxidation. The extent of inhibition by TRF varied with different peroxidation products such as conjugated dienes, lipid hydroperoxides and thiobarbituric acid reactive substances (TBARS). Among the constituents of TRF, γ-tocotrienol was the most effective followed by its α- and δ-isomers. In general, at a low concentration of 5 μM, TRF was able to prevent oxidative damage to significant extent (37% inhibition of protein oxidation and 27–30% of lipid peroxidation at 1 h of incubation). The protective ability of TRF (30.1% at 5 μM with TBARS formation) was significantly higher than that of the dominant form of vitamin E, α-tocopherol (16.5% under same conditions). Hence our studies indicate that this fraction from palm oil can be considered as an effective natural antioxidant supplement capable of protecting cellular membranes against oxidative damage.

Lipid peroxidation in rat uterus

Lipid peroxidation in rat uterus has been studied using NADPH- and ascorbate-induced systems. Lipid peroxidation in rat uterus is low as compared to rat liver. Uterus is more sensitive to ascorbate-induced lipid peroxidation than that induced by NADPH. Uterus contains lower amounts of phospholipids and has a lesser degree of unsaturation in lipids. Co-factor studies show that Fe2+ is more important for ascorbate-induced lipid peroxidation. Endometrium is more sensitive to ascorbate-induced lipid peroxidation than myometrium. It also contains more total lipids and phospholipids besides having a higher degree of unsaturation in the lipids as compared to myometrium. Among the subcellular fractions, mitochondria are more prone to ascorbate-induced lipid peroxidation, whereas microsomes are more sensitive to NADPH-induced lipid peroxidation. Uteri from old rats (24 months) and pregnant rats are more resistant to lipid peroxidation than those from 3-month-old control rats. Uterus of pregnant rats contains more factors which inhibit lipid peroxidation and also has a lesser degree of unsaturation in lipids compared with uterus of control rats. The possible consequences of the resistance of uterus to lipid peroxidation, especially during pregnancy and senescence, are discussed.

Chlorophyllin as an effective antioxidant against membrane damage in vitro and ex vivo

Chlorophyllin (CHL), the sodium-copper salt and the water-soluble analogue of the ubiquitous green pigment chlorophyll, has been attributed to have several beneficial properties. Its antioxidant ability, however, has not been examined in detail. Using rat liver mitochondria as model system and various sources for the generation of reactive oxygen species (ROS) we have examined the membrane-protective properties of CHL both under in vitro and ex vivo conditions. Oxidative damage to proteins was assessed as inactivation of the enzymes, cytochrome c oxidase and succinic dehydrogenase besides formation of protein carbonyls. Damage to membrane lipids was measured by formation of lipid hydroperoxides and thiobarbituric acid reactive substances. The effect of this compound on the antioxidant defense system was studied by estimating the level of glutathione and superoxide dismutase. ROS were generated by gamma-radiation, photosensitization, ascorbate-Fe(2+), NADPH-ADP-Fe(3+) and the peroxyl radical generating agent, azobis-amidopropane hydrochloride. Our results show that CHL is highly effective in protecting mitochondria, even at a low concentration of 10 microM. The antioxidant ability, at equimolar concentration, was more than that observed with ascorbic acid, glutathione, mannitol and tert-butanol. When CHL was fed to mice at a dose of 1% in drinking water, there was a significant reduction in the potential for oxidative damage in cell suspensions from liver, brain and testis. To examine the possible mechanisms responsible for the observed antioxidant ability we have studied the reaction of CHL with the potent ROS in the form of hydroxyl radical and singlet oxygen. The compound shows a fairly high rate constant with singlet oxygen, in the order of 1.3x10(8) M(-1) s(-1). In conclusion, our studies showed that CHL is a highly effective antioxidant, capable of protecting mitochondria against oxidative damage induced by various ROS.