, there would be around 62 million patients with coronary artery disease ( cad ) by 2015 in india and of these , 23 million would be patients younger than 40 years of age . cad is due to atherosclerosis of large- and medium - sized arteries , and dyslipidemia has been found to be one of the most important contributing factors [ national cholesterol education program , the adult treatment panel iii ( ncep , atp iii ) ] . during the past three decades , dyslipidemia as a risk factor for cvd has increased markedly in india . currently available hypolipidemic drugs ( statins ) have been associated with a number of side effects . patients on treatment with crystalline niacin or extended - release niacin showed significant elevation in alt and risk of hepatotoxicity is much greater with slow - release niacin . increases in plasma creatinine from 15% to 20% are common in fibrate - treated patients and more significant increases can occur in patients with underlying renal disease . research interest has focused on various herbs that possess hypolipidemic effect that may be helpful adjunct in reducing the risks of cvd . it has been used for centuries with claimed efficacy and safety in treatment of jaundice , liver disorders and various skin disorders . it consists picrorrhiza kurroa ( kutki ) , terminalia chebula ( haritaki ) , terminalia bellerica ( bibhitaka ) , emblica officinalis ( amalaki ) , asphaltum ( silajatu ) , commiphora wightii ( guggulu ) , ricinus communis ( eranda ) , azadirachta indica ( neem leaves ) and metal including suddh rasa ( detoxified mercury ) , gandhaka suddha ( detoxified sulfur ) , lauha - bhasma ( iron ) , abhraka bhasma ( mica ) , tamra bhasma ( copper ) . the findings of the study showed that arogyavardhini vati in the doses equivalent to 10 times of the human dose , administered to rats for 28 days , do not have appreciable toxicological effects on brain , liver , and kidney . endothelial dysfunction plays a vital role in triggering ischemic events in the development of cvd . c - reactive protein ( crp ) , an acute phase protein , has been clinically used as a sensitive marker for systemic inflammation . therapies have been developed to lower hs - crp concentrations and reduce the potential risk factor for cvds . there are plethora of clinical and experimental studies showing that antioxidants such as vitamin e have been shown to reduce the oxidative susceptibility of lipoproteins and may have anti - atherosclerotic effects . in hypercholesterolemic animal models , epidemiologic studies also indicate an inverse association between the intake of vitamin e and coronary heart disease . hence , considering the antioxidant , anti - inflammatory and hypolipidemic property , the present study was designed to study the effect of arogyavardhini vati in triton wr-1339-induced hyperlipidemia in rats . male wistar rats ( 150 - 200 g ) were used in the present study . the animals were obtained from the central animal facility , all india institute of medical sciences , new delhi and stock bred in the departmental animal house . the rats were group - housed in polyacrylic cages ( 38  23  10 cm ) with not more than four animals per cage and maintained under standard laboratory conditions with natural dark and light cycle . they were allowed free access to standard dry diet ( ashirwad , punjab , india ) and tap water ad - libitum . all experimental procedures described were reviewed and approved by the institutional animal ethics committee , all india institute of medical sciences , new delhi india ( 497/iaec/09 ) . arogyavardhini vati was purchased from the gmp certified company ( maharshi ayurveda pharmaceutical limited , new delhi , india ) . triton wr-1339 was purchased from sigma - aldrcih ( st . louis , mo , usa ) and dissolved in dmso . the first group was given standard pellet diet , water and administered intraperitoneal injection of 4% dmso . the second hyperlipidemic group received triton wr-1339 dissolved in 4% dmso ( 400 mg / kg body weight ) . after 72 h of triton injection , this group received a daily dose of 4% dmso ( p.o . ) for 7 days . third group was administered with the standard fenofibrate ( 65 mg / kg , p.o . ) for 7 days . the fourth , fifth , and sixth group was administered daily doses of arogyavrdhini vati ( 50 , 100 , 200 mg / kg , p.o . ) for 7 days , after inducing hyperlipidemia . human equivalent rat dose of 500 , 1000 , and 2000 mg will be 50 , 100 , and 200 mg / kg ( human to rat dose conversion factor is 6 and average human body weight is 60 kg ) . the doses of arogyavardhini vati ( 50 , 100 , 200 mg / kg ) in rat was calculated by extrapolating the equivalent human dose ( therapeutic dose , sub - maximum , and maximum dose ) and was administered orally between 10 and 11 a.m. daily for 7 days , in a volume not exceeding 1 ml/100 g rat weight . after 12 h of treatment , animals were anesthetized with diethyl ether and blood was withdrawn from retro - orbital sinus . the blood samples were immediately centrifuged ( 3000 rpm for 10 min ) and serum was used to estimate the levels of total cholesterol , triglyceride , ldl , and hdl using semi - auto analyzer ( mini techno , newark , de 19711 , usa ) according to the instruction of manufacturer of assay kits ( logitech india pvt . the level of serum crp was estimated by elisa , according to the instruction of manufacturer of assay kits ( life diagnostics inc . , mill valley , ca 94941 , usa ; catalog number : 2210 - 21-hr ) . cardiac risk was determined by estimating its atherogenic index ( ai = tc / hdl - c ) as stated by malaspina . animals were euthanized and liver was removed to determine the levels of mda and gsh . malondialdehyde , an indicator of lipid peroxidation was determined by the method of ohkawa et al . glutathione was measured according to the method of ellman and concentration was expressed as mg / g - wet tissue . a one - way analysis of variance ( anova ) , followed by tukey 's test was used for statistical analysis . spss ( version 16 ) statistical software was used for the analysis of data and p < 0.05 was taken as the level of significance . male wistar rats ( 150 - 200 g ) were used in the present study . the animals were obtained from the central animal facility , all india institute of medical sciences , new delhi and stock bred in the departmental animal house . the rats were group - housed in polyacrylic cages ( 38  23  10 cm ) with not more than four animals per cage and maintained under standard laboratory conditions with natural dark and light cycle . they were allowed free access to standard dry diet ( ashirwad , punjab , india ) and tap water ad - libitum . all experimental procedures described were reviewed and approved by the institutional animal ethics committee , all india institute of medical sciences , new delhi india ( 497/iaec/09 ) . arogyavardhini vati was purchased from the gmp certified company ( maharshi ayurveda pharmaceutical limited , new delhi , india ) . triton wr-1339 was purchased from sigma - aldrcih ( st . louis , mo , usa ) and dissolved in dmso . the first group was given standard pellet diet , water and administered intraperitoneal injection of 4% dmso . the second hyperlipidemic group received triton wr-1339 dissolved in 4% dmso ( 400 mg / kg body weight ) . after 72 h of triton injection , this group received a daily dose of 4% dmso ( p.o . ) for 7 days . third group was administered with the standard fenofibrate ( 65 mg / kg , p.o . ) for 7 days . the fourth , fifth , and sixth group was administered daily doses of arogyavrdhini vati ( 50 , 100 , 200 mg / kg , p.o . ) for 7 days , after inducing hyperlipidemia . human equivalent rat dose of 500 , 1000 , and 2000 mg will be 50 , 100 , and 200 mg / kg ( human to rat dose conversion factor is 6 and average human body weight is 60 kg ) . the doses of arogyavardhini vati ( 50 , 100 , 200 mg / kg ) in rat was calculated by extrapolating the equivalent human dose ( therapeutic dose , sub - maximum , and maximum dose ) and was administered orally between 10 and 11 a.m. daily for 7 days , in a volume not exceeding 1 ml/100 g rat weight . after 12 h of treatment , animals were anesthetized with diethyl ether and blood was withdrawn from retro - orbital sinus . the blood samples were immediately centrifuged ( 3000 rpm for 10 min ) and serum was used to estimate the levels of total cholesterol , triglyceride , ldl , and hdl using semi - auto analyzer ( mini techno , newark , de 19711 , usa ) according to the instruction of manufacturer of assay kits ( logitech india pvt . ltd . , the level of serum crp was estimated by elisa , according to the instruction of manufacturer of assay kits ( life diagnostics inc . , mill valley , ca 94941 , usa ; catalog number : 2210 - 21-hr ) . cardiac risk was determined by estimating its atherogenic index ( ai = tc / hdl - c ) as stated by malaspina . animals were euthanized and liver was removed to determine the levels of mda and gsh . malondialdehyde , an indicator of lipid peroxidation was determined by the method of ohkawa et al . glutathione was measured according to the method of ellman and concentration was expressed as mg / g - wet tissue . a one - way analysis of variance ( anova ) , followed by tukey 's test was used for statistical analysis . spss ( version 16 ) statistical software was used for the analysis of data and p < 0.05 was taken as the level of significance . the serum total cholesterol , triglycerides , ldl , and hdl levels were measured in normal and triton wr-1339-induced rats [ table 1 ] . there was significant increase in serum total cholesterol , triglycerides , and ldl levels and decreased hdl levels in triton - induced hyperlipidemic rats . administration of arogyavardhini vati at doses of 50 , 100 , 200 mg / kg and standard drug fenofibrate ( 65 mg / kg ) significantly decreased serum total cholesterol , triglycerides , and ldl , and increased hdl when compared with triton - induced hyperlipidemic rats ( p < 0.001 ) . there were no statistically significant differences in the level of serum total cholesterol , triglycerides , ldl , and hdl in fenofibrate - treated rats as well as normal control rats . effect of arogyavardhini vati on serum lipid profiles and c - reactive protein in the rats crp level was increased in triton - treated rats . fenofibrate ( 65 mg / kg ) treated rats showed significant decrease in crp levels when compared with triton - treated rats ; however levels were raised when compared with normal control . there was no significant change in the level of crp at low dose of arogyavardhini vati ( 50 mg / kg ) when compared with triton- treated rats . however , significant decrease in the level of crp was observed at higher doses ( 100 and 200 mg / kg ) of arogyavardhini vati ( p < 0.001 ) . there was no statistical significant difference in the level of crp at maximum dose of arogyavardhini vati ( 200 mg / kg ) when compared with fenofibrate - treated rats [ table 1 ] . there was significant decrease in liver mda and increased gsh level observed at all doses of arogyavardhini vati ( 50 , 100 , 200 mg / kg ) and fenofibrate ( 65 mg / kg ) treated rats when compared with triton - treated rats ( p < 0.001 ) . a significant increased mda and decreased gsh levels in liver of triton - treated rats ( p < 0.001 ) was observed when compared with normal control . there was significant decrease in mda and increased gsh was observed in a dose - dependent manner [ table 2 ] . effect of arogyavardhini vati on liver oxidative stress marker ( mda and reduced glutathione levels ) in the rats treatment with arogyavardhini vati ( 50 , 100 , 200 mg / kg ) in triton wr-1339-induced dyslipidemic rats significantly decreased ai level in a dose - dependent manner when compared with triton - treated rats ( p < 0.001 ) . there was no statistically significant change in the level of ai in fenofibrate ( 65 mg / kg ) treated rats and maximum dose of arogyavardhini vati ( 200 mg / kg ) treated rats when compared with normal control [ figure 1 ] . values are expressed as mean  sem , n = 6 , p < 0.001 , a when compared with normal control ; b when compared with triton - treated group , c when compared with fenofibrate - treated group the serum total cholesterol , triglycerides , ldl , and hdl levels were measured in normal and triton wr-1339-induced rats [ table 1 ] . there was significant increase in serum total cholesterol , triglycerides , and ldl levels and decreased hdl levels in triton - induced hyperlipidemic rats . administration of arogyavardhini vati at doses of 50 , 100 , 200 mg / kg and standard drug fenofibrate ( 65 mg / kg ) significantly decreased serum total cholesterol , triglycerides , and ldl , and increased hdl when compared with triton - induced hyperlipidemic rats ( p < 0.001 ) . there were no statistically significant differences in the level of serum total cholesterol , triglycerides , ldl , and hdl in fenofibrate - treated rats as well as normal control rats . effect of arogyavardhini vati on serum lipid profiles and c - reactive protein in the rats fenofibrate ( 65 mg / kg ) treated rats showed significant decrease in crp levels when compared with triton - treated rats ; however levels were raised when compared with normal control . there was no significant change in the level of crp at low dose of arogyavardhini vati ( 50 mg / kg ) when compared with triton- treated rats . however , significant decrease in the level of crp was observed at higher doses ( 100 and 200 mg / kg ) of arogyavardhini vati ( p < 0.001 ) . there was no statistical significant difference in the level of crp at maximum dose of arogyavardhini vati ( 200 mg / kg ) when compared with fenofibrate - treated rats [ table 1 ] . there was significant decrease in liver mda and increased gsh level observed at all doses of arogyavardhini vati ( 50 , 100 , 200 mg / kg ) and fenofibrate ( 65 mg / kg ) treated rats when compared with triton - treated rats ( p < 0.001 ) . a significant increased mda and decreased gsh levels in liver of triton - treated rats ( p < 0.001 ) was observed when compared with normal control . there was significant decrease in mda and increased gsh was observed in a dose - dependent manner [ table 2 ] . effect of arogyavardhini vati on liver oxidative stress marker ( mda and reduced glutathione levels ) in the rats treatment with arogyavardhini vati ( 50 , 100 , 200 mg / kg ) in triton wr-1339-induced dyslipidemic rats significantly decreased ai level in a dose - dependent manner when compared with triton - treated rats ( p < 0.001 ) . there was no statistically significant change in the level of ai in fenofibrate ( 65 mg / kg ) treated rats and maximum dose of arogyavardhini vati ( 200 mg / kg ) treated rats when compared with normal control [ figure 1 ] . values are expressed as mean  sem , n = 6 , p < 0.001 , a when compared with normal control ; b when compared with triton - treated group , c when compared with fenofibrate - treated group atherosclerotic cad is one of the major causes of premature death globally and it is expected to be the most important cause of mortality in india . there are several lines of evidence with respect to the fact that hdl cholesterol is inversely related to total body cholesterol and a reduction of plasma hdl cholesterol concentration may accelerate the development of atheroscelerosis leading to ischemic heart diseases , by impairing the clearing of cholesterol from the arterial wall . there is plethora of studies which has investigated the plants for their acute hypolipidemic activity in triton wr-1339-induced hyperlipidemic animals . triton wr-1339 injection results increase in plasma cholesterol and triglycerides due to increase in vldl secretion by the liver accompanied by a strong reduction of vldl - c and ldl - c catabolism . fenofibrate ( 65 mg / kg ) treated group was taken as positive control because it is effective in hypertriglyceridemia and hypercholesterolemia . it has been well established that nutritional supplements such as herbal medicinal products , vitamin e , etc . our present study clearly shows that arogyavardhini vati significantly lowered serum total cholesterol , triglycerides , and ldl levels , and increased hdl in a dose - dependent manner ( 50 , 100 , 200 mg / kg ) [ table 1 ] . the treatment with arogyavardhini vati also reduced the ai which is an important and sensitive indicator to determine the cardiac risk [ figure 1 ] . there are several components of arogyavardhini vati which are known to have hypolipidemic effects , i.e. , picrorrhiza kurroa , terminalia chebula , terminalia bellerica , emblica officinalis , and guggulu . the mechanisms by which arogyavardhini vati exerted the beneficial effects is presently not clear . ellagitannins and the ellagic acid obtained on hydrolysis of these tannins ( by lipases and/or esterases ) are inhibitors of squalene epoxidase , a rate - limiting enzyme of cholesterol biosynthesis . inflammation is known to reduce hdl and the enhancement of hdl observed in the present study may arise from the control of inflammation by arogyavardhini vati . the serum crp level which is a marker of systemic infection was significantly reduced at the end of the treatment in our study which are also reported in literature . therefore , it is likely that a reduction in serum lipid levels observed in the present study by arogyvardhini vati may be mediated through above mechanisms . lipid peroxidation is the most commonly used parameters for assessing oxidative damage in the human body . in this process ldl - c and other lipid containing molecules may be oxidized in the blood stream , exerting adverse effects on a variety of processes like inhibiting antithrombin iii activity , producing procoagulant activity , enhancing platelet aggregation , modulating vascular responses , and acting as mitogen . the formation and activation of atherosclerotic lesion is a multi - faceted process involving many determinants , including oxidative modification of ldl . oxidized ldl causes foam cell formation , leukocyte adhesion to the endothelium , cytotoxicity , and vascular endothelial dysfunction leading to impaired edno synthesis and biological activity . in the present study , arogyavardhini vati administration caused a significant reduction of liver mda and increased gsh level [ table 2 ] . lowering of oxidative stress with concomitant lowering of cholesterol indicated that there was reduced oxidative stress after administration of arogyavardhini vati in a dose - dependent manner . the results of present study indicate antiatherosclerotic roles of arogyavardhini vati which can indirect effect due to enhanced lipid metabolism by liver . this study showed that the liver antioxidants induced by arogyavardhini vati may have protective effect against ldl oxidation , thereby preventing or slowing the events leading to the initiation of atherosclerosis . the observation made from this study showed that arogyavardhini vati possesses a stronger antioxidant potential . arogyavardhini vati may be a useful therapy for hypercholesterolemia through reducing oxidative stress ( decreasing mda and increasing gsh ) and lipid levels ( decreasing serum total cholesterol , triglyceride , ldl levels and increasing serum hdl level ) . the results of the present animal study pave the path to conduct clinical study and arogyavarhdini vati was found to be safe and efficacious in dyslipidemia patients .