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Abstract.

Saraca asoka (Family - Caesalpiniaceae) has been widely used in the Ayurvedic (traditional Indian) system of medicine especially due to its wound healing property. The present study investigated the chemopreventive property of flavonoids from the flowers of Saraca asoka on 7,12 dimethyl benz(a)anthracene (DMBA) induced skin cancer in mice models. A single topical application of DMBA (100 microg/50 microL of acetone) followed after 2 weeks by three times a week treatment with croton oil (1% in acetone), for 20 weeks resulted in tumor induction. The topical application of the flavonoid fraction of S. asoka (FF S. asoka), 30 min prior to the application of croton oil thrice weekly for 20 weeks, caused a significant reduction in the number of tumors per mouse and the percentage of tumor-bearing mice. Also the latency period for the appearance of the first tumor was delayed by S. asoka pretreatment. In the flavonoid fraction (5 mg and 10 mg/kg body weight) treated animals, the levels of biochemical markers - rhodanese, myeloperoxidase, beta-D-glucuronidase, sialic acid, hexokinase and caspase 3 were significantly restored to near normal levels. These findings suggest the chemopreventive activity of flavonoids from S. asoka on two stage skin Carcinogenesis. Histological data also support the chemopreventive potential of S. asoka.

Cullen WJ, Dulchavsky SA, Devasagayam TP, Venkataraman BV, Dutta S. Effect of Maharishi AK-4 on H2O2-induced oxidative stress in isolated rat hearts. J EthnoPharmacol. 1997;56(3):215-22. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Oxidative damage to crucial bioMolecules due to excess generation of reactive oxygen species has been implicated as a major cause of organ damage and hence compounds capable of negating such damage have potential benefits. Using hydrogen peroxide (H2O2) as a model pro-oxidant to induce oxidative stress, we have examined the ability of natural food supplement Maharishi Amrit Kalash (MAK-4) to decrease oxidative damage in potassium-arrested isolated rat hearts. The protocol was that hearts isolated from male Sprague-Dawley rats were retrograde-perfused with Krebs-Henseleit (K-H) solution for 30 min for equilibration. After this period, the hearts were subjected to cardioplegia with high potassium (26-30 mM), followed by reperfusion with K-H solution in the presence or absence of 200 microM H2O2. As expected, H2O2 treatment following cardioplegia induced a high degree of oxidative stress as assessed by release of lactate dehydrogenase (LDH, a marker of plasma membrane damage) and total glutathione (GSH + GSSG). H2O2 also impaired the ability of heart to regain developed tension during the testing period. However, addition of MAK-4 in the perfusate containing H2O2 decreased oxidative stress in terms of release of LDH and glutathione. In parallel with these biochemical studies, in a few experiments the cardiac function was assessed by measuring developed contractile tension. These preliminary studies also showed that in the presence of MAK-4 the H2O2-treated hearts were able to regain better developed tension. Further in vitro studies to examine the possible mechanisms of MAK-4 action reveal that this formulation contains H2O2 binding activity which resulted in the decreased availability of H2O2 itself. Our studies hence reveal that the Ayurvedic food supplement MAK-4 may have potential benefits in reducing oxidative stress.

Das Sanjita, Sarkar PK, Sengupta A, Chattopadhyay A.A Clinical Study of Aragvadha (Cassia fistula Linn) on Vicharchica (Eczema). The Journal of Research and Education in Indian Medicine.2008;14(2):27-32.

Abstract.

Vicharchika (eczema) is a chronic skin disease with no permanent cure in modern medicine. Raised serum IgE level is the commonest immunological marker for eczema. Aragvadha (Cassia fistula linn) is a well known, commonly used plant in various anti-iching and Kusthaghna anti- leprotic properties. In the present study Aragvadha fruit pulp has been evaluated for its Kusthaghna activety on the patients of Vicharchika (eczema). The results of this study are suggestive of significant efficacy of Aragvadha on the patients of Vicharchika (eczema).

Dang GK, Parekar RR, Kamat SK, Scindia AM, Rege NN. Antiinflammatory activity of Phyllanthus emblica, Plumbago zeylanica and Cyperus rotundus in acute models of inflammation. Phytother Res. 2010.Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Experimental studies conducted earlier have proved that Phyllanthus emblica (Pe), Plumbago zeylanica (Pz) and Cyperus rotundus (Cr), plants from the medohara group of Ayurveda possess antiatherosclerotic activity. As inflammation is also one of the pathophysiological factors, it was of interest to evaluate whether these drugs exhibit any antiinflammatory activity. Two models of acute inflammation, namely carrageenan induced rat paw edema and acetic acid induced peritonitis in mice were used. In the model of carrageenan induced paw edema Pe, Pz and Cr showed a trend to reduce the edema while the combination of Pe + Pz (PI: 20.64%) showed results comparable to aspirin (23.74%). Whereas in a model of acetic acid induced peritonitis, all the plant drugs i.e. Pe, Pz, Cr and a combination of Pe + Pz showed a significant decrease in the protein content of the peritoneal exudates compared with the disease control group (p < 0.05), however, only Pe + Pz exhibited activity comparable to aspirin. Copyright © 2010 John Wiley and Sons, Ltd.

Datta GK, Sairam K, Priyambada S, Debnath PK, Goel RK. Antiulcerogenic activity of Satavari mandur--an Ayurvedic herbo-mineral preparation. Indian J Exp Biol. 2002;40(10):1173-7. http://www.ncbi.nlm.nih.gov/

Abstract.

Satavari mandur (SM) is a herbo-mineral preparation containing Asparagus racemosus, which finds mention in ancient Indian texts for treatment of gastric ulcers. The ulcer protective effect of SM, 125-500 mg/kg given orally, twice daily for three, five and seven days, was studied on cold restraint stress-induced gastric ulcer in rats. The effective regimen was found to be 250 mg/kg given for five days and hence was used for further experiments. SM showed significant protection against acute gastric ulcers induced by pyloric ligation but was ineffective against aspirin- and ethanol-induced ulcers. Further, gastric juice studies showed that, SM significantly increased the mucosal defensive factors like mucus secretion, but had little or no effect on offensive factors like acid and pepsin secretion.

D'cruz SC, Mathur PP. Effect of piperine on the epididymis of adult male rats. Asian J Androl. 2005;7(4):363-8. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

METHODS:

Adult male rats were orally administered piperine at doses of 1 mg/kg, 10 mg/kg and 100 mg/kg body weight each day for 30 consecutive days. Twenty-four hours after the last treatment, the rats were weighed and killed with ether and the epididymis was dissected from the bodies. Sperm collected from the cauda region of the epididymis was used for the assessment of its count, motility and viability. Caput, corpus and cauda regions of the epididymis were separated and homogenized separately to obtain 10 % homogenates. The supernatants were used for the assays of sialic acid, superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, lipid peroxidation and hydrogen peroxide generation.

RESULTS:

Body weight of the piperine-treated rats remained unchanged. The weights of the caput, corpus and cauda regions of the epididymis significantly decreased at dose of 100 mg/kg. Epididymal sperm count and motility decreased at 10 mg/kg and 100 mg/kg, and sperm viability decreased significantly at 100 mg/kg. Sialic acid levels in the epididymis decreased significantly at 100 mg/kg while significant decrease in the cauda region alone was observed at 10 mg/kg. A significant decline in the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, along with an increase in hydrogen peroxide generation and lipid peroxidation were observed at 10 mg/kg and 100 mg/kg.

CONCLUSION:

Piperine caused a decrease in the activity of antioxidant enzymes and sialic acid levels in the epididymis and thereby increased reactive oxygen species levels that could damage the epididymal environment and sperm function.

Deep G, Dhiman M, Rao AR, Kale RK. Chemopreventive potential of Triphala (a composite Indian drug) on benzo (a)pyrene induced forestomach tumorigenesis in murine tumor model system. J Exp Clin Cancer Res. 2005;24(4):555-63. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

The present work is probably the first report on cancer chemopreventive potential of Triphala, a combination of fruit powder of three different plants namely Terminalia chebula, Terminalia belerica and Emblica officinalis. Triphala is a popular formulation of the Ayurvedic system of medicine. Our findings have shown that Triphala in diet has significantly reduced the benzo(a)pyrene [B(a)P] induced forestomach papillomagenesis in mice. In the short term treatment groups, the tumor incidences were lowered to 77.77% by both doses of Triphala mixed diet. In the case of long-term treatment the tumor incidences were reduced to 66.66% and 62.50% respectively by 2.5% and 5% Triphala containing diet. Tumor burden was 7.27 +/- 1.16 in the B(a)P treated control group, whereas it reduced to 3.00 +/- 0.82 (p < 0.005) by 2.5% dose and 2.33 +/- 1.03 (p < 0.001) by 5% dose of Triphala. In long-term studies the tumor burden was reduced to 2.17 +/- 0.75 (p < 0.001) and 2.00 +/- 0.71 (p < 0.001) by 2.5% and 5% diet of Triphala, respectively. It was important to observe that Triphala was more effective in reducing tumor incidences compared to its individual constituents. Triphala also significantly increased the antioxidant status of animals which might have contributed to the chemoprevention. It was inferred that the concomitant use of multiple agents seemed to have a high degree of chemoprevention potential.

Deokota Rajeev, Chhetri RB. Traditional medication in Bhedetar of district Sunsari(Nepal). Ethnobotany.2009;21:112-115.

Abstract.

Present study communicates the documentation of thirty-eight medicinal plants for indigenous medication by the Magar, Tamang, Rai, and Limbu tribes of Bhedetar in Sunsari district of Nepal. These plants are used to cure different ailmates like wounds, fever, cough, muscle pain, skin diseases, dysentery, diarrhea, jaundice and stomach pain on the advice and with the help of the local healers in day-to-day life of these ethnic groups.

Desai VR, Ramkrishnan R, Chintalwar GJ, Sainis KB. G1-4A, an immunomodulatory polysaccharide from Tinospora cordifolia, modulates macrophage responses and protects mice against lipopolysaccharide induced endotoxic shock. Int ImmunoPharmacol. 2007;7(10):1375-86. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Pro-inflammatory cytokines are known to be the mediators of endotoxic shock and several immunomodulatory herbs can modulate the expression of these cytokines. Therefore we have investigated the possibility of using an arabinogalactan polysaccharide, G1-4A, from the stem of Tinospora cordifolia, for protection against endotoxin induced sepsis. There was 100% protection against lipopolysaccharide (LPS) induced mortality in mice pretreated with G1-4A. To elucidate the mechanism of action, its effect on macrophages, the primary source of these pro-inflammatory Molecules was evaluated. G1-4A was shown to bind to the murine macrophages leading to their activation and reciprocally inhibited binding of LPS to macrophages. Following treatment with G1-4A, there was a small increase in serum TNF-alpha and IL-1beta levels. However, challenge with LPS elicited significantly reduced levels of TNF-alpha in G1-4A pretreated mice as compared to the controls while the level of soluble TNFR was enhanced. An increase in serum IL-1beta, IL-6, IFN-gamma levels and decrease in that of IL-10 was observed following challenge with LPS in mice pretreated with G1-4A as compared to the controls. In addition, G1-4A also modulated the release of nitric oxide by murine macrophages. Similar phenomenon was observed in a human monocytic cell line, U937. Thus G1-4A appeared to induce tolerance against endotoxic shock by modulation of cytokines and nitric oxide.

Devi KP, Sreepriya M, Balakrishna K, Devaki T. Protective effect of Premna tomentosa extract (L. verbanacae) on acetaminophen-induced mitochondrial dysfunction in rats. Mol Cell Biochem. 2005 ;272(1-2):171-7. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Allurement of herbs as health beneficial foods (physiologically functional foods) and as a source material for the development of new drugs, has led to greater furtherance in the study of herbal medicines during recent years. Plant extracts are being utilized to treat a wide variety of diseases like hepatotoxicity. Premna tomentosa is one such medicinal plant used widely in Indian Ayurvedic medicine for the treatment of liver disorders. This study appraised the effectiveness of P. tomentosa leaf extract in protecting the liver against mitochondrial damage induced by acetaminophen, since mitochondrial injury hasbeen investigated as a potential initiator of hepatotoxicity. Normal Wistar strain rats were pre-treated with P. tomentosa extract (750 mg/kg, orally) for 15 days and then intoxicated with acetaminophen (640 mg/kg, orally). Mitochondria were isolated from liver of experimental animals and assessed for the levels of lipid peroxide products, GSH and mitochondrial enzymes (isocitrate dehydrogenase, alpha-keto glutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH dehydrogenase and cytochrome-C-oxidase). The levels of Lipid peroxidation products were increased and the levels of the other assessed parameters were significantly decreased in hepatotoxicity induced animals. Whereas, the levels were brought back to normal in P. tomentosa pre-treated rats, which shows the protective effect of the extract against mitochondrial damage. Presence of anti-oxidant compound D-limonene (58%) in P. tomentosa leaves, which is known to enhance conjugation of toxic metabolites by maintaining liver GSH concentrations may explain the hepatoprotective property of the extract.

Dhanasekaran M, Holcomb LA, Hitt AR, Tharakan B, Porter JW, Young KA, Manyam BV. Centella asiatica extract selectively decreases amyloid beta levels in hippocampus of Alzheimer's disease animal model. Phytother Res. 2009;23(1):14-9. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

PSAPP mice expressing the 'Swedish' amyloid precursor protein and the M146L presenilin 1 mutations are a well-characterized model for spontaneous amyloid beta plaque formation. Centella asiatica has a long history of use in India as a memory enhancing drug in Ayurvedic literature. The study investigated whether Centella asiatica extract (CaE) can alter the amyloid pathology in PSAPP mice by administering CaE (2.5 or 5.0 g/kg/day) stArting at 2 months of age prior to the onset of detectable amyloid deposition and continued for either 2 months or 8 months. A significant decrease in amyloid beta 1-40 and 1-42 was detectable by ELISA following an 8 month treatment with 2.5 mg/kg of CaE. A reduction in Congo Red stained fibrillar amyloid plaques was detected with the 5.0 mg/kg CaE dose and long-term treatment regimen. It was also confirmed that CaE functions as an antioxidant in vitro, scavenging free radicals, reducing lipid peroxidation and protecting against DNA damage. The data indicate that CaE can impact the amyloid cascade altering amyloid beta pathology in the brains of PSAPP mice and modulating components of the oxidative stress response that has been implicated in the neurodegenerative changes that occur with Alzheimer's disease

Dhanasekaran M, Tharakan B, Holcomb LA, Hitt AR, Young KA, Manyam BV. Neuroprotective mechanisms of Ayurvedic antidementia botanical Bacopa monniera. Phytother Res. 2007;21(10):965-9. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Alzheimer's disease is a neurodegenerative disorder characterized by progressive dementia. Bacopa monniera is described in the Ayurvedic Materia Medica, as a therapeutically useful herb for the treatment of cognitive impairment, thus supporting its possible anti-Alzheimer's properties. Our studies have shown that Bacopa monniera reduces beta-amyloid deposits in the brain of an Alzheimer's disease animal model. The objective of this study was to establish the presence of endogenous substances in Bacopa monniera extract (BmE) that will impact components of the oxidative stress cascade such as the reduction of divalent metals, scavenging of reactive oxygen species, alterations of lipoxygenase activity and hydrogen peroxide-induced lipid peroxidation. The extract contained polyphenols and sulfhydryl contents suggestive of endogenous antioxidant activity. The results demonstrated that BmE reduced divalent metals, dose-dependently scavenged reactive oxygen species, decreased the formation of lipid peroxides and inhibited lipoxygenase activity. These data combined with our previous studies that have shown that BmE treatment reduces beta-amyloid levels in the brain of an Alzheimer's disease doubly transgenic mouse model of rapid amyloid deposition (PSAPP mice) suggesting mechanisms of action relevant to thetreatment of Alzheimer's disease.

Dhanasekaran M, Tharakan B, Manyam BV. Antiparkinson drug--Mucuna pruriens shows antioxidant and metal chelating activity. Phytother Res. 2008;22(1):6-11. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Parkinson's disease is a neurodegenerative disorder for which no neurorestorative therapeutic treatment is currently available. Oxidative stress plays an important role in the pathophysiology of Parkinson's disease. The ancient Indian medical system, Ayurveda, traditionally uses Mucuna pruriens to treat Parkinson's disease. In our earlier studies, Mucuna pruriens has been shown to possess antiparkinson and neuroprotective effects in animal models of Parkinson's disease. The antioxidant activity of Mucuna pruriens was demonstrated by its ability to scavenge DPPH radicals, ABTS radicals and reactive oxygen species. Mucuna pruriens significantly inhibited the oxidation of lipids and deoxyribose sugar. Mucuna pruriens exhibited divalent iron chelating activity and did not show any genotoxic/mutagenic effect on the plasmid DNA. These results suggest that the neuroprotective and neurorestorative effect of Mucuna pruriens may be related to its antioxidant activity independent of the symptomatic effect. In addition, the drug appears to be therapeutically safe in the treatment of patients with Parkinson's disease

Dhuley JN. Nootropic-like effect of ashwagandha (Withania somnifera L.) in mice. Phytother Res. 2001;15(6):524-8. Retraction in: Williamson EM. Phytother Res. 2008;22(10):1416. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Ashwagandha (Withania somnifera L.) root extract (50, 100 and 200 mg/kg; orally) improved retention of a passive avoidance task in a step-down paradigm in mice. Ashwagandha (50, 100 and 200 mg/kg; orally) also reversed the scopolamine (0.3 mg/kg)-induced disruption of acquisition and retention and attenuated the amnesia produced by acute treatment with electroconvulsive shock (ECS), immediately after training. Chronic treatment with ECS, for 6 successive days at 24 h intervals, disrupted memory consolidation on day 7. Daily administration of ashwagandha for 6 days significantly improved memory consolidation in mice receiving chronic ECS treatment. Ashwagandha, administered on day 7, also attenuated the disruption of memory consolidation produced by chronic treatment with ECS. On the elevated plus-maze, ashwagandha reversed the scopolamine (0.3 mg/kg)-induced delay in transfer latency on day 1. On the basis of these findings, it is suggested that ashwagandha exhibits a nootropic-like effect in naive and amnesic mice.

Dhuley JN. Adaptogenic and cardioprotective action of ashwagandha in rats and frogs. J EthnoPharmacol. 2000;70(1):57-63. Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Pharmacological and metabolic effects of ashwagandha (Withania somnifera L. (Solanaceae)) used in Ayurveda as a herbal tonic and health food were studied. Ashwagandha was shown to increase swimming time in rats in physical working capacity test, i.e. rats swimming endurance test. Significant increase in relative heart weight and glycogen content in myocardium and liver was also observed in ashwagandha treated group. Ashwagandha treatment increased the duration of contractility in functional test for the resistance of frog heart muscle towards the toxic action of strophanthin-K. Ashwaaandha treatment also resulted in significant increase in coagulation time which attains normalcy 7 days after cessation of treatment. Ashwagandha possesses no toxicity up to a dose of (100 mg/kg; p.o. for 180 days) and does not cause significant changes in biochemical parameters in the blood serum of rats. Increase in catecholamine content in the heart and aortic tissues and their decrease in adrenal glands are unfavourable effects of high doses of ashwagandha. On the basis of these observations, it was concluded that ashwagandha possesses adaptogenic, cardiotropic, cardioprotective and anticoagulant properties.

Dhuley JN. Hepatoprotective effect of rhinax on antitubercular drug-induced hepato-toxicity in rats. Hindustan Antibiot Bull. 2002;44(1-4):53-9.Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Rhinax, a polyherbal formulation, exhibited hepatoprotective function when tested against antitubercular drug-induced hepatotoxicity in rats. Suppression of GSH and antioxidant enzymes "superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), gultathionle peroxidase (GPx) and glutathione S-transferase (GST) were noticed in the liver of antitubercular chemotherapeutic agents (namely isoniazid, rifampicin and pyrazinamide) treated animals accompanied with an increase in cytochrome P-450 contents and increased production of lipid peroxidation. Rhinax afforded hepatoprotection by inhibiting lipid peroxidation and, as a result, the animals showed improved antioxidant status.

Ding X, Staudinger JL. The ratio of constitutive androstane receptor to pregnane X receptor determines the activity of guggulsterone against the Cyp2b10 promoter. J Pharmacol Exp Ther.2005;314(1):120-7.Http://www.ncbi.nlm.nih.gov/pubmed/.

Abstract.

Guggulsterone is the active ingredient in gugulipid, an organic extract of the Commiphora mukul plant. Gugulipid has been used for nearly 3000 years in Ayurvedic medicine, mainly as a treatment for arthritis. Herbal practitioners currently use gugulipid therapy in conditions as diverse as rheumatism, coronary artery disease, arthritis, hyperlipidemia, acne, and obesity. The active ingredient in gugulipid is guggulsterone, a plant sterol compound recently identified as a pregnane X receptor (PXR; NR1I2) ligand. We show herein that guggulsterone treatment represses the expression of cytochrome P450 2b10 (Cyp2b10) gene expression by inhibiting constitutive androstane receptor (CAR; NR1I3) activity in hepatocytes lacking functional PXR (PXR-knockout). We also show that PXR-CAR cross-talk determines the net activity of guggulsterone treatment toward Cyp2b10 gene expression. Using mammalian two-hybrid assays, we show that treatment with guggulsterone differentially affects protein cofactor recruitment to these two nuclear receptors. These data identify guggulsterone as an inverse agonist of the nuclear receptor CAR. When viewed together with the data showing that PXR and CAR expression is highly variable in different ethnic populations and that CAR expression is under the control of a circadian rhythm, our data provide important insight into the molecular mechanism of interindividual variability of drug Metabolism. These data, together with the recent resolution of the crystal structures of PXR and CAR, will likely aid in the rational design of more specific CAR inverse agonists that are currently viewed as potential antiobesity drugs.




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