Studying the antihyperlipidaemic basis of ayurvedic formulations –Avipattikara churna and triphala churna

Dixit Praveen K*1, Nagarajan K2, Kumar Sokindra3 1Department of Pharmacology. KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh,201206 Af iliated to Dr APJ Abdul Kalam Technical University, Lucknow, U.P, India 2Department of Pharmaceutical Chemistry. KIET School of Pharmacy, KIET Group of Institutions, Delhi-NCR, Ghaziabad, Uttar Pradesh,201206, Af iliated to Dr APJ Abdul Kalam Technical University, Lucknow, U.P, India 3Department of Pharmacology ,Kharvel Subharti College of Pharmacy, Swami Vivekanand Subharti University, Meerut,250005, Uttar Pradesh, India


INTRODUCTION
The lipids are signi icant biomolecules. Cholesterol is a vital component of the human cell membrane, and they are a major precursor to steroid hormones and bile acids. Even triglycerides play a signi icant function in transmitting energy from food to body cells. Any excess biomolecule is not ideal for human health; however, (Kanakavalli et al., 2014) . Hyperlipidemia has been described as one of the major risk factors which are responsible for the development and severity of coronary heart diseases (Saravanakumar et al., 2010) . Atherosclerosis risk fac-tors are affected by hyperlipidemia, hypertension, obesity, elevated coagulation factor and homocysteine.
In that dyslipidemia, the most critical risk factor in the elderly population causes ischemic heart disease (IHD). IHD's fundamental mechanism involves the accumulation of serum lipids in coronary arteries, leading to the reduced blood supply to cardiac muscles. (Talha et al., 2014) Present lipid modulating drugs include ibrates, bile-acid sequestrates, cholesterol absorption inhibitors, nicotinic acid, phytosterols, protein transfer inhibitors to cholesteryl ester, ish oil, and HMG-CoA reductase inhibitors. Clinically, statins were the medicines most widely prescribed for hypercholesterolemia. Statins help minimize plasma concentration of low-density lipoprotein cholesterol (LDLC) and decrease coronary artery disease mortality and morbidity. (Sailesh et al., 2013)Over the ages, spices have been eaten in many cultures. Because of their taste and scent, they were eaten mainly. Nevertheless, recent scienti ic indings have demonstrated their biological activity beyond their taste and smell. Spices are now known for their anti-thrombotic, antiatherosclerotic, hypolipidemic, hypotensive, antiin lammatory, anti-arthritic and platelet aggregation inhibitors activity. Clinical studies have shown that hypercholesterolemia is a signi icant risk factor for coronary artery disease (CAD) in which lowdensity lipoprotein (LDL) cholesterol plays a signi icant role in atherosclerosis and pathogenesis of CAD and other vascular diseases is one of the major reason for premature death globally and is expected to be one of the leading cause of death in India by 2021. (El-Yamani, 2011) Consumption of prescription medications with side effects such as hyperuricemia, vomiting, nausea, myositis, stomach pain, lushing, dry skin and impaired liver function. Triphala is a typical Ayurvedic herbal remedy consisting of equal parts of three medicinal plants, namely Terminalia chebula, Terminalia belerica and Phyllanthus Emblica. Triphala is considered a 'tridosic rasayan' with calming and rejuvenating effects in the Charaka Samihita on the three constitutional elements that rule human life, i.e., Vata, Pitta and Kapha. (Sailesh et al., 2013) , (Jing et al., 2017) . Avipattikar Churna is an Ayurvedic medicine used to treat gastrointestinal complaints. This is helpful for constipation and gastritis treatment. It contains strong medicinal herbs, helps to promote digestive tract functions and relieves the symptoms of certain diseases, and can also be used to treat urinary disorders, including dif iculties passing through urine. Combined ingredients of Avipattikara ChurnaTable 1 and Triphala Churna Table 2 play an essential role in hypolipidemic behaviour. They indicate that the lipid-lowering action is mediated by inhibiting the biosynthesis of hepatic cholesterol and reducing lipid absorption in the intestine. Hyperlipidemia prevalence is in the range of 39 per cent, 51 per cent and 26 per cent respectively globally, developed and developing countries. Overall, cholesterol elevated is estimated to cause 2.6 million deaths (4.5 per cent of the total) and 29.7 million life-adjusted disability years, or 2.0 per cent of overall. (Kanakavalli et al., 2014) Medicinal plants are used for various purposes of the study. More than 15,000 plants for speci ic pharmacological properties were researched and documented. The pharmacological study observations for various components drug of Triphala Churna and Avipattikar Churna are as following.

Cinnamomum Tamala(Patra)
A study was performed to investigate the CTO and Cinnamaldehyde potential on diabetic rats with the oral administration of 100 or 200 mg/kg and 20 mg/kg, respectively, for 28 days to study both acute and chronic anti-hyperglycemic models. The whole activity in study was compared with the Glibenclamide, 0.6 mg/kg, as standard drug and shown to be as effective as standard in reducing the glucose level and beta-cell existing insulin potentiation. (El-Yamani, 2011) Ethanolic extraction of C. Tamala leaves display hypoglycemic activity and anti-hyperglycemic. It also corrects blood glucose levels to normal and substantially raises total cholesterol, TG, LDL and VLDL cholesterol levels in diabetic rats, and decreases chances of hyperlipidemia following daily dose. C. Tamala leaf extract facilitates the releasement of insulin from undestroyed β-cells and enhances oral glucose tolerance by increasing insulin availability. (Kumar et al., 2012) Aqueous and ethanolic Cinnamomum Tamala Nees leaf extracts. Doses of 400mg / kg / day p.o were administered. Each leaf extract for ten days signi icantly (p<0.001) prevents a rise in the serum levels of total cholesterol, triglyceride, LDLC, VLDL-C and Atherogenic index whereas substantial (p<0.01) increases in HDL-C. (Kanakavalli et al., 2014) In male Wistar strain albino rats, the antihyperlipidemic effect of aqueous extract from the Cinnamomum Tamala leaf (CTLE) was evaluated at two graded doses levels viz., bodyweight: 200 and 400 mg/kg. The following two models have been used in rat for anti-hyperlipidemic activity, high fat diet, and hyperlipidemia induced by Tri-  ton X-100. The ef icacy of CTLE in Triton X100induced hyperlipidemia was contrasted with standard Atorvastatin (10 mg/kg, p.o.) and in the highfat diet with Atorvastatin (30 mg/kg, p.o.). The indings show that CTLE has a signi icant potential for anti-hyperlipidemic by reducing TC, TG, LDL-C and increasing HDL-C. (Saravanakumar et al., 2010) The analysis was examined for the extract of leaves C. Tamala with an oral dosage of 100, 200 and 400 mg/kg, given once daily for seven days and with effectiveness compared by lorazepam (1 mg/kg, p.o.), imipramine (10 mg/kg, p.o.). The study showed that the rats treated with CT reported a substantial decrease in plasma triglyceride levels and LDL-C levels. (Singh et al., 2016) Speci ic doses of C. tamala extract was orally administered for 15 d to alloxan-induced diabetic rats and was monitored for the impact of treatment on blood glucose levels, glycosylated haemoglobin and peroxidation products such as thiobarbituric acid reactive substances and serum lipids. These studies have given proof of C. tamala ethanol extract's anti-diabetic, antioxidant and anti-hyperlipidemic activity when orally administered. (Singh et al., 2016) Cyperus Scariosus(Nutgrass) The researchers have studied the antioxidant and lipid-lowering function of a Cyperus scariosus Linn root hydroalcoholic extract (HCS) on guinea pigs dieting high in cholesterol. Both doses of Cyperus scariosus hydroalcoholic extract decreased the serum lipid pro ile and atherogenic indices (P < 0.05). (Singh et al., 2018b) Research to investigate the lipid-lowering and antioxidant function of a hydroalcoholic extract of C. scariosus Linn. root (HCS) in guinea pigs fed with a high cholesterol diet was evaluated. Serum lipid pro ile (TC, VLDL-C, TG, LDL-C, and HDL-C), serum enzymes (ALT, AST, ALP, LDH, and CK-MB) and atherogenic indices were performed in each group at 0 days and 60 days, respectively. (Kumar et al., 2017) Antihyperglycemic activity calculated by the glucose tolerance test in mice showed that a dosage of 400 mg/kg glibenclamide extract was as active as 10 mg/kg. (Chawda et al., 2014) Elletaria Cardamomum (Suksmaila) The various study aims to assess the antioxidant role of Cardamom (Elettaria cardamomum) on oxidative damage caused by gamma radiation in liver and heart tissues. The analysis was carried out on forty (40) rats categorized into four regular classes. A signi icant enhance (P=0.05) in the TC, TG, and LDL-C levels correlated with a substantial decrease (P=0.05) in HDL-C was seen in irradiated rat serum. The hyperlipidaemic condition found after irradiation may be due to the bloodstream mobilizing the fats from the adipose tissue. (Venkatasubramanian et al., 2015) A study was done to examine the cardamom extract's antihyperlipidemic behaviour for Wistar albino rats being fed a high-fat diet. The present experimental research provides further evidence that a signi icant anti-hyperlipidemic effect occurred during 30 days of oral administration of cardamom extract. Cardamomum powder suspension was tested for ef icacy with pioglitazone on dexamethasone-induced dyslipidemia, hyperglycemia in albino rats at a dose of 45 mg/kg orally, and an increase in total cholesterol, triglycerides, and decrease in HDL was observed in the group of dexamethasone, and a substantial reduction in total cholesterol and triglyceride, as well as an increase in HDL. (Darwish et al., 2013) In Wistar rats, the anti-hypercholesterolemic activity of cardamom was tested by inducing eight weeks of hypercholesterolemia with high cholesterol, and dietary treatments with cardamom powder (50g / kg) showed a substantial reduction in total blood cholesterol (31%) and LDL cholesterol (44%) through oral administration and 3% reduction in liver triglycerides. (Bhat et al., 2015) Embelica Ribes(Vidanga) The Embelica ribes (ethanolic extract) administered orally at the concentration of 200 mg/kg for 20 days reported substantial (p<0.01) reduction in serum total cholesterol and triglycerides, blood glucose levels and increased rates of HDL cholesterol compared with streptozotocin-induced pathogenic diabetic rats (with a dose of 40 mg/kg, IV). (Nagashree et al., 2017) A study performed for the lipidreduction of ethanolic extract E. Ribes were investigated in streptozotocin-induced diabetes at a dosage of 40 mg/kg in rats for 20 days of oral extract feeding at the dose of 200 mg/kg in diabetic rats, resulting in substantial decreases in blood glucose, total serum cholesterol and triglycerides, and elevated levels of HDL cholesterol compared with pathogenic diabetic rats. (Srinath et al., 2010) (Kumar et al., 2012) Bioassay-guided isolation of the Piper longum L and piper nigram fruit from an ethanol extract. The major anti-hyperlipidemic constituents were piperlonguminine, piperine, and pipernonaline. Both demonstrate substantial anti-hyperlipidemic activity in vivo, which is comparable to that of simvastatin, the commercial anti-hyperlipidemic drug. (Md et al., 2019) The antihyperlipidaemic activity of chemically synthesized GBN in rats was irst tested and veri ied in a study. The indings of in vivo antihyperlipidaemic assay showed that there were critical lipid-lowering activities in synthetic GBN. (Jin et al., 2009) In High-fat diet-induced study, obese rats were treated orally with 200 mg/kg b.wt of various extracts as (hexane, ethanol, aqueous, etc.) of PnL at 42 d. The levels of total cholesterol, TGs, PLs, HDL-C, LDL-C, and VLDL-C are recorded in control plasma and liver and HFD-fed rats. A substantial increase in tissue and plasma lipid pro iles was observed, which was substantially reduced by oral administration. (Sarnaizul et al., 2013) Therefore, the piperine-induced increase in the receptor-mediated clearance of apoB-containing lipoproteins and decrease in the hepatic apoB production by testosterone may explain the decreased apoB levels. Thus, the administering of piperine enhances the high-fat-induced changes in hormone pro iles and the function of signi icant apolipoproteins and decreases plasma lipid levels. (Parim et al., 2015), (Vijayakumar and Nalini, 2006)

Saccharum of icinarum (Sarkara)
The effect of policosanol (obtained from Saccharum of icinarum) and Atorvastatin on blood lipid proile and the aggregation of platelet in dyslipidaemia along with type 2 diabetes patients. Policosanol consistently decreased LDL-C by 25.7% after eight weeks of therapy, and total cholesterol (TC) by 18.2%. In effect, atorvastatin 10 mg/day signi icantly decreased LDL-C by 41.9% and TC by 31.5 per cent. (Vijayakumar and Nalini, 2006) A proportion of polysaccharides from S. of icinarum on the metabolism of carbohydrate and lipid in normal rats were tested and those diets high in sugar. Feeding with a high sugar diet caused serum glucose elevation and massive accumulation of lipid peroxide in the serum and liver. Combined feeding with the polysaccharide fraction has prevented the production of lipid peroxides. The dosage of the policosanol used in human studies ranged from 2, 40 to 80 mg/day. Some research reported a substantial decrease in plasma cholesterol between 5 weeks and 8 weeks at doses of 5 and 10 mg, respectively. As a standard drug, it was compared with statins, and the result indicated an ef icient lipid pro ile potential but above 80mg/ kg The results of the metaanalysis showed that TC and LDL-C could be lowered and HDL-c increased by sugarcane polycosanol.
No signi icant impacts were observed on TG and body weight. The most potent therapeutic effects of sugarcane policosanol should be achieved with a daily dosage of 5 mg, and lipid-improving effects did not occur in a dosage-dependent manner. (Francini-Pesenti et al., 2008)

Zinger of icinale Roscoe (Sunthi)
Protective effect of ginger on blood pressure and on blood lipid pro ile in rats which is fed on a high-fat diet (HFD) and comparison was made with another natural herbal garlic's preventive effect, which is a studied more and a proven herb against these risk factors. The result was that ginger is an essential herbal remedy against IHD risk factors (hypertension and hyperlipidemia). (Jing et al., 2017) Speci ic doses of ginger powder (range 13 g) were used in the clinical trials over various periods (range 45 days-12 weeks). The result that has been found was ginger, particularly in diabetic patients, can be considered as a useful ingredient for modifying blood lipids. (Saravanan et al., 2007) The ultimate aim of the study is to investigate the ability of ginger extract (GIN) to modulate the expression and activity of liver SCD1 under hyperlipidemic conditions, to reduce the accumulation of lipids in the steatotic liver. Results can be a signi icant help for developing a new strategy to minimize lipid accumulation and oxidative stress in the steatotic liver to enhance its proper functioning. (Sanghal et al., 2012) The research was planned to assess and compare the ef icacy of different doses of Ginger decoction with rosuvastatin, feno ibrate and ezetimibe in hyperlipidemic rats on lipid pro ile, liver function test and MDA level and it reported to have an effective potential. (Arablou and Aryaeian, 2018) Red Ginger Rhizomes Ethanol Extract (RGREE) administered at 100 mg/kg, and 400 mg/kg daily doses have the potential to boost lipid pro ile including decreasing levels of cholesterol and triglycerides, as well as rising blood plasma levels of HDLs. (Carnuta et al., 2018) Although treatment with methanolic extract of Zingiber of icinale dried rhizomes resulted in a substantial reduction in fructose-induced lipidlevel elevation, body weight, hyperglycemia, and hyperinsulinemia, treatment with Zingiber of icinale ethyl acetate extract did not bring about any significant improvement in any of the last two parameters. (Dizaye et al., 2019) Terminalia chebula (Haritaki) The effect of Terminalia chebula fruit ethanolic extract, given orally for 30 days at the concentration of 500mg / kg (Dose-A) & 250mg / kg (Dose-B) and extract showed a substantial decrease in the cholesterol and triglyceride serum levels in hyperlipidemic rats. (Sa itri et al., 2016) There is ample evidence that it can be used as an anti-ageing agent for gastrointestinal motility. It also has properties such as Antilithiatic activity, Hypolipidemic activity, Ability-protecting Radio, Antifungal activity, and so forth. (Kadnur and Goyal, 2005) Treatment with Terminalia chebula (300mg / kg, p.o) and its combination with Gaumutra (30mg / kg, p.o) showed substantial decreases (p<0.05) in serum and tissue serum and tissue cholesterol, LDL-C, VLDL-C, triglycerides, atherogenic indexes and increased levels of HDL-C. (Choudhary, 2013) (Israni et al., 2010) The Terminalia chebula Retz aqueous extract of fruits shows anti-diabetic activity in the rat by using streptozotocin (STZ) induced model and activity compared with tolbutamide, a known drug. The extract's oral effective dose (ED) was found to be 200 mg/kg body weight, resulting in a 55.6% (p < 0.01) decrease in the oral glucose tolerance study.

Terminalia bellerica (Bibhitaki)
T. bellerica fruit ethanolic extract 250mg / kg & 500mg / kg body weight was administered p.o., Evaluate the anti-hyperlipidemic response for 20 days. The indings of this study show that T. bellerica alcoholic extract (500 mg / Kg) has a substantial decrease in different levels of lipid as well as the elevated physical parameters such as heart weight, body weight ratio, BMI. Orlistat and Atorvastatin are used as standard drugs. (Reddy et al., 2015) , (Murali et al., 2007) In rabbits, cholesterol feeding was experimentally caused by hypercholesterolaemia and atherosclerosis. These hypercholesterolemic rabbits measured the impact of an endogenous drug, T bellerica. T bellerica decreased lipid concentrations in hypercholesterolemic animals. The drug-treated animals have reported a substantial diminish in liver lipids and heart lipids (P < 0.05). (Pragya et al., 2016) Terminalia bellerica is the rich source of the existence in plant fruit extracts of β-sitosterol, gallic acid, ellagic acid, galactose, ethyl gallate, chebulagic acid, mannitol, glucose, galactose, fructose and rhamnose, and these constituents had several investigated successful lipid pro ile potentials. (Ahmad and Mishra, 2017) Syzygium aromaticum (Lavanga) The present work was carried out to examine the role of clove bud powder (CBP) on type 2 diabetes rat model, which is induced for 30 days by using high-fat diet along with streptozotocin (35 mg kg−1), and the result revealed the dose-dependent action potential of the Syzygium aromaticum. (Shaila et al., 1995) Lipid peroxidation as demonstrated by a rise in the values of TBARS, CD, urea, lipid pro iles, AST and ALT as well as a distinct decrease in GSH rates in hyperlipidaemic rats was found to be nulliied by co-administration of cloves as these parameters showed a propensity to return to near normalcy. (Singh et al., 2018a) The experiments were carried out after six weeks by using the high-fat diet-fed (control group) and high-fat diet + lycopene (10 mg/kg) (test group). Serum TC, LDL -C and serum TG levels decreased dramatically, and serum HDL -C and antioxidant SOD increased following the addition of lycopene to a high-fat diet Hyperlipidaemia was induced in rats over six weeks by oral administration of a high-fat diet. The extract was then given to hyperlipidaemic rats for the next six weeks, at two separate doses of 200mg / kg and 400mg / kg body weight. Atorvastatin was used as a norm of reference. The extract exhibited dosedependent anti-hyperlipidaemic activity. (Shyamala et al., 2003) The ultimate results of the present study showed that Eugenia caryophyllus responsible for anti-hyperlipidemic activity against hyperlipidaemia induced by high-fat diet at (200mg / kg) and high (400mg / kg) dosages. (Mulkalwar et al., 2002;Shyamala et al., 2003;Kadnur and Goyal, 2005) , (Ghai et al., 2015) CONCLUSIONS Several potential therapies for hyperlipidaemia are recently being investigated. The current statins and ibrates therapy, which regularly fails to emulate the lipid homeostasis that healthy individuals eventuate. It is widely reported that herbal sources are more useful, having fewer side effects and convenient as far as the administration is concerned. So, the only answers can be explored form the Ayurvedic Polyherbal formulations. In this review, authors are trying to discuss exhaustively the Avipattikar and Triphala churna constituents which have tremendous potential to cure and prevent the problem of hyperlipidaemia.