International Journal of Agronomy and Plant Production. Vol., 4 (11), 2906-2911, 2013 Available online at http:// www.ijappjournal.

com ISSN 2051-1914 2013 VictorQuest Publications

Hypocholestrolemic activity of plants: A Review

M. Akram , Abdul Hamid , Khalil Ahmed , Abdul Ghaffar , Tayyaba Naveed , Saeed Ahmed , S. M. Ali 1 7 Shah , Naveed Akhtar 1- Department of Eastern Medicine and Surgery, University of Poonch, Rawalakot, Azad Jammu and Kashmir, Pakistan 2- Department of Horticulture, Faculty of agriculture, University of Poonch, Rawalakot, Azad Jammu and Kashmir, Pakistan 3-University College of Conventional Medicine, the Islamia University. 4- Department of life sciences, The Islamia University of Bahawalpur, Pakistan 5- Department of Applied Psychology, Bahauddin Zakaria University Sub Campus Sahiwal 6- Cholistan Institute of Desert Studies, the Islamia University of Bahawalpur 7- Faculty of Pharmacy, the Islamia University of Bahawalpur *Corresponding Author: M. Akram Abstract People are increasingly turning to medicinal plants to treat hypercholesterolemia. Plants are involved in deceasing cholesterol level. The material for this review was taken mostly from Biochemistry textbooks & electronic journal Up-to-date. To collect publication PubMed and the Cochrane database of systematic reviews was used. Some other relevant references were collected from personal database of papers on efficacy of plants in hypercholesterolemia, phytotherapy of hypercholesterolemia, hypercholesterolemia and medicinal plants etc. Various medicinal plants having hypocholestrolemic activity include such as Prunus amygdalus Batsch, Boswellia serrata, Moringa oleifera Lam, Salvia officinalis, Aegle marmelos, Butea monosperma, Asparagus officinalis Linn, Capparis spinosa, Allium cepa Linn, Allium sativum Linn, Anethum graveolens and Ananas comosus L. These medicinal plants can be further studied for isolation of active ingredients responsible for activity. Keywords: Hypercholesterolemia, herbs, efficacy, medicinal plants, literature review. Abbreviation: WHO: World health organization, LDL: Low-density lipoprotein, HepG2 cells: cell line derived from the liver carcinoma of a Caucasian adolescent, HMG CoA: 3-hydroxy 3 methyl glutaryl Co-A Introduction This is a steroid that us present in the diet, but it is mainly synthesized in the liver and small intestine, the rate limiting step being catalysed by beta hydroxyl-beta methylglutaryl-coenzyme A (HMG Co-A) reductase. Cholesterol is a major component of cell membranes, and acts as the substrate for steroid hormone formation in the adrenals and the gonads. It is present in plasma mainly esterified with fatty acids. The body can not break down the sterol nucleus, so cholesterol is either excreted unchanged in bile or converted to bile acids and then excreted. Cholesterol and bile acids both undergo an enterohepatic circulation. Medicinal plants play a vital role in treatment of diseases. More than 2000 plants listed in the traditional (Herbal / Alternative) systems of medicine are prescribed to treat hyperlipidemia. They provide complete relief for people suffering from hypercholesterolemia. World health organization (WHO) reports indicate that about eighty percent of the global population still relies on various botanical medicines and herbal drugs have progressed to clinical use of modern
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times (Saad et al, 2010). Medicinal plants are now a day very popular among Unani physicians. They are preferred mainly due to easy availability in market, cheaper as compare to allopathic drugs, fewer side effects and desirable effects. There are various medicinal plants which are used for treatment of hypercholesterolemia. Various research studies have been conducted on medicinal plants regarding to their hypocholestrolemic activity. Plants produce an amazing variety of metabolites such as isoflavones, phytosterols, saponins, fiber, polyphenols, flavonoids and ascorbic acid, which have generated great interest both for its role in lipid metabolism and antioxidant. Many more medicinal plants are used to treat hypercholestrolemia, but here in this paper those medicinal plants are discussed which are usually prescribed in the management of hypercholestrolemia. This report gives the information about anti-hypercholestrolemic plants. In 2006, Sudhahar et al has reported the role of lupeol and lupeol linolate on lipemic-oxidative stress in experimental hypercholesteromia (Sudhahar et al, 2006). Chen et al has reported that Hibscus sabdariffa extract inhibit the development of atherosclerosis in cholesterol-fed rabbits (Chen et al., 2003). Malinow et al has reported the Alfalfa is potentially useful for treatment of hypercholesterolemia (Malinow et al, 1977). Hirunpanich et al has reported the hypocholesterolemic and antioxidant effects of aqueous extracts from the dried calyx of Hibiscus sabdariffa L. in hypercholesterolemic rats (Hirunpanich et al, 2006). Salleh et al has reported the inhibition of low-density lipoprotein oxidation and upregulation of low-density lipoprotein receptor in HepG2 cells (cell line derived from the liver carcinoma of a Caucasian adolescent) by tropical plant extracts (Salleh et al., 2002). Bustos et al has reported the HMG CoA (3hydroxy 3 methyl glutaryl Co-A) reductase inhibition by atorvastatin reduces inflammation in a rabbit model of atherosclerosis (Bustos et al, 1998). Based on these findings, this review is written for the documentation of medicinal plant commonly used to treat hypercholestrolemia. Methods The material for this review was taken mostly from Biochemistry textbooks & electronic journal Up-to-date. To collect publication PubMed and the Cochrane database of systematic reviews was used. Some other relevant references were collected from personal database of papers on efficacy of plants in hypercholesterolemia, phytotherapy of hypercholesterolemia, hypercholesterolemia and medicinal plants Medicinal plants with anti-hypercholestrolemic and related beneficial properties Prunus amygdalus Batsch Family: Rosaceae, Part used: fruit. It relieves cough, resolves phlegm and lubricates lungs. Berryman et al has reported the efficacy of almond consumption to reduce LDL (low density lipoprotein)-cholesterol (Berryman et al., 2011). Study: A study conducted by Teotia et al (1997) demonstrated that Prunus amygdalus is antihypercholestrolemic agent. In this study, 36 normolipidemic male albino rats were selected. This study was of 60 days duration. Total cholesterol, triglycerides and bad cholesterol (LDL) was significantly decreased. There was an increase in phospholipid, faecal sterol and HDL cholesterol (Teotia et al., 1997) Moringa oleifera Lam Family: Moringaceae, Part used: Bark, fruit, flower, leaves, seeds and gum. It is used to treat various ailments. The pods are rich in vitamins and minerals. It is a good source of linolinic acid. It contains galactose, dextrose, xylose, sodium, potassium, calcium, magnesium, glucouronic acid, alkaloids, resin, inorganic acid and gum. It is antispasmodic, stimulant, expectorant and diuretic. Roots are acrid and vesicant. It is antibiotic and laxative. It is prescribed in upper respiratory tract infections. It is anti-inflammatory agent and is prescribed to treat gout and rheumatoid arthritis. It is antioxidant and is used to treat cardiovascular disorders. It is antimicribial agent and used to treat diarrhea. It is antihyperlipidemic and is prescribed by herbal physician to treat obesity. It is antifertility agent and is used to treat libido and impotence. It has anticancer and is prescribed to treat carcinoma of lungs. It is antihepatotoxic and is used to treat jaundice and other liver disorders. It has antiulcer and is prescribed to treat peptic ulcer. It is antispasmodic and is prescribed to treat abdominal pain. It is diuretic and is prescribed to treat kidney stones and urinary tract infections. Study: Ghasi et al has reported the hypocholesterolemic effects of crude extract of leaf of Moringa oleifera Lam in high-fat diet fed wistar rats. Hypocholestrolemic activity of Moringa oleifera leaves was investigated in high fat diet fed rats. When Moringa oleifera with high fat diet was administered to rats, there was decrease in high fat diet induced serum cholesterol. This decrease was 14.35% (115-103.2 mg/100 ml of serum) in cholesterol level. There was significant reduction in serum cholesterol level. Serum total protein was not altered significant. Serum albumin level was increased by 15.22% (46-53 g/l). This value was also statistically significant. This study showed that Moringa oleifera has

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hypocholesterolemic effect and validates the use of Moringa oleifera in traditional system of medicine(Ghasi et al., 2000). Salvia officinalis Family: Lamiaceae, Part used: Leaves. This common culinary herb has many home heath care applications and is easily preserved by drying bundled sprigs. Sage tea can be used as a gargle for sore throats, mouth ulcers, and gingivitis, and it has a high mineral content. Sage often contains figures in formulas for premenstrual syndrome. Study: Kianbakht et al has reported the antihyperlipidemic effects of Salvia officinalis L. leaf extract in patients with hyperlipidemia. In a randomized clinical trial, 67 hyperlipidemic patients were selected, whose mean age was 54 years. Treatment duration was 2 months. Dose of extract was 500 mg capsule every 8 h for 2 months. In 33 patients , lipids, creatinine, SGOT and SGPT were evaluated in comparison with placebo group having 33 patinets. There was significant decrease in total cholesterol, triglyceride, LDL and VLDL and HDL level were increased. There was no significant alteration in levels of SGOT, SGPT and creatinine compared with the placebo group. There were no significant side effects. Study showed that it is effective to treat hyperlipidemia (Kianbakht et al., 2011). Aegle marmelos Family: Rutaceae, Part used: Leaves. Devi et al has reported the hypolipidemic Effect of Aegle marmelos Leaf Extract in Streptozotocin Induced Diabetic Male Albino Rats (Devi et al., 2010). Study: 50% ethanolic extract of the leaves of A. marmelos (Linn.) was investigated for its efficacy to lower lipid levels. Hyperlipidemia was induced by triton and diet in Wistar albino rats. Dose of extract was 125 and 250 mg/kg dose. Serum cholesterol and triglycerides levels were decreased on Triton WR 1339 administration in rats. There was significant reduction in serum cholesterol level in diet induced hyperlipidemic rats. HDL levels were found elevated in fat induced hyperlipidaemic rats (Vijaya et al., 2009) Butea monosperma Family: Fabaceae, Part used: Leaves, stem bark and flowers. This plant is prescribed to treat intestinal worm infestations. It is used to treat piles. It has anti-cancer activity. It is found effective in gastrointestinal disorders. It is used to treat sprue. It is prescribed to treat pelvic inflammatory diseases, orchitis, swelling, boils and pimples. It is prescribed to treat bleeding in cattle. Study: Dixit et al has reported the anti-obese activity of Butea monosperma (Lam) bark extract in experimentally induced obese rats. Butea monosperma bark was investigated to its anti-obesity effect in cafeteria and atherogenic diet fed rats and monosodium glutamate (MSG) obese rats. Different doses of extracts were used and there was dose dependent response on obesity. Doses give were 200, 400 and 800 mg/kg of Butea monosperma extract. There was significant reduction in body weight. This study showed that plant has anti-obesity effect and can be used to treat hypercholesterolemia(Dixit et al., 2012). Asparagus officinalis Linn Family: Liliaceae, Part used: Shoot. The plant has tuberous or fleshy roots. The flowers are very small and greenish, and the fruit is a berry. The plant has no true leaves, which are reduced to scales or rare replaced by flat, leaf like branches. The young, tender hoots of the plant are used as a vegetable. Study: Hypolipidemic activity of n-butanol extract (BEA) from asparagus by-products was investigated in high fat diet induced hyperlipidemic mice. There was significant reduction in body weight, total cholesterol level and bad cholesterol (LDL) by the use of n-butanol extract. This study was of 8 weeks. Dose of extract was 40, 80 or 160 mg/kg body weight. There was significant increase in level of HDL. This study showed its hypolipidemic activity (Zhu et al., 2011) Capparis spinosa Family: Capparaceae, Part used: Root and shoot. This plant is prescribed to treat inflammatory disorders. It is prescribed by Unani physician to treat gouty arthritis, rheumatoid arthritis and osteoarthritis. It has anticancer activity. Study: Eddouks et al has reported the hypolipidemic activity of aqueous extract of Capparis spinosa L in normal and diabetic rats. Hypolipidemic activity of Capparis spinosa was investigated in normal and streptozocin induced diabetic rats. Dose of drug was 20mg/kg. Extract was administered orally. There was significant reduction in triglyceride level in normal rats after one week of dose administration. In diabetic rats, lipid level was also decreased after repeated oral administration. There was significant decrease in body weight in diabetic rats

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after repeated oral treatment in diabetic rats. This study indicated that extract has lipid lowering efficacy in normal and diabetic rats at 20 mg/kg (Eddouks et al., 2005). Allium cepa Linn Family: Liliaceae, Part used: Bulb. Bulbs of this plant are used to treat various ailments. It exhibits potential inhibitory effect on collagen induced aggregation of human platelets; it has high fungitoxic activity and antimicrobial activity. Onion juice is aphrodisiac, hypoglycemic, stimulant, diuretic and expectorant. It is lipid lowering agent. It is used to treat hypercholesterolemia. Sebastian et al has reported the hypolipidemic effect of onion (Allium cepa Linn) in sucrose fed rabbits (Sebastian et al., 1979). Study: S-methyl cysteine sulfoxide (SMCS) isolated from Allium cepa Linn has been investigated for its hypolipidemic activity in Sprague-Dawley rats fed on 1% cholesterol diet, in comparison to the hypolipidemic drug gugulipid. Duration of study was 45 days. Dose of drug was 200mg/kg body weight. Drug exhibited lipid lowering effect. There was significant decrease in cholesterol, triglyceride and phospholipids as compared to their untreated counterparts. Free fatty acid level was decreased due to decrease activity of lipase in the adipose tissue. Lipogenic enzymes remained low such as glucose 6-phosphate dehydrogenase and malic enzyme. HMG CoA reductase level was also reduced. There was significant reduction in lipogenesis and cholesterogenesis in the hyperlipidemic animals. There was increase excretion of bile acids and sterols in feces. Endogenous lipogenesis was also decreased. This study indicates its lipid lowering efficacy (Kumari et al., 2006) Allium sativum Linn Family: Liliaceae, Part used: Bulb. Chemical constituents: Scordinine, alicin, alliin, volatile oil, acrolein, phytocidin, diallyl trisulphide, diallyl-disulphide. It is used to treat various ailments. Garlic shows anti-tubercular activity. The volatile oil and its components are reported to posses hepatoprotective activity. It prevented free radical formation and lipidperoxidation. The garlic extract is also used as antiarthritis, anti-inflammatory, stimulant, asthma and whooping cough. It is hypocholestrolemic agent and is prescribed to treat hyperlipidemia. Study: Augusti et al has reported the beneficial effects of garlic (Allium sativum Linn) on rats fed with diets containing cholesterol. 2% cholesterol diet was fed that resulted in increased level of lipid. 5% Allium sativa was administered to rats. Lipid level, their peroxidation and enzymes level was significantly decreased. This study shows that Allium sativa has hypocholestrolemic activity (Augusti et al, 2001). Anethum graveolens Family: Umbelliferae, Parts used: Leaves. Chemical constituents: Monogalactosyl and digalactosyl are the main constituents of glycolipid. Phosphatidylglycerol is predominant in leaves where as phosphatidylcholine is predominant in stem. The major fatty acids present are linolenic acid and palmitic acid. Carvene, dihydrocarvene, D-limonene, phellandrene, terpene are also reported. Dill oil is powerful pesticide, aromatic, and carminative properties have also been reported. It is hypolipidemic and is prescribed to treat hyperlipidemia. Study: Yazdanparast et al has reported the antihyperlipidaemic and antihypercholesterolaemic effects of Anethum graveolens leaves. Water extract of Anethum graveolens was investigated in diet induced hypercholestrolemic rats. Duration of study was 14 days. There was significant reduction in total cholesterol level. After this observation, furocoumarins was isolated from the aqueous extracts of Anethum graveolens and was administered to investigate its efficacy to lower cholesterol. Chloroform extract of furocoumarin was did not show anti-hyperlipidemic activity significantly. After this, essential oil of Anethum graveolens was administered orally at two different doses. 42% reduction in triacylglyceride was observed. This study indicates that Anethum graveolens has hypocholestrolemic activity (Yazdanparast et al., 2001). Ananas comosus L Family: Bromeliaceae, Parts used: Leaves. Chemical constituents:Bromelin, ergasterol peroxide, ash and vitamin C. Study: Xie et al has reported the hypolipidemic mechanisms of Ananas comosus L. leaves in mice. Hypolipidemic activity was investigated in fructose fed mice. Study showed that Ananas comosus at a dose of 0.40 g/kg significantly lowered serum triglycerides by 40%. When high fed diet was given to mice, serum cholesterol level was increased that remained high within 7 days of removing high-fat diets and was rapidly decreased by administering Ananas comosus. Ananas comosus at a dose of 0.40 and 0.80 g/kg was able to inhibit serum lipids from the increase in Triton WR-1339-induced hyperlipidemic mice. Lipoprotein lipase was activated and 3-hydroxyl-methyl glutaryl coenzyme A (HMGCoA) reductase was inhibited in vitro. In a further study, fenofibrates administration increased mice liver weights and Ananas comosus had no effect on liver mice.

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This study indicated that Ananas comosus could be a new alternative drug of herbal origin for the treatment of hyperlipidemia that exhibits its activity by inhibition of HMGCoA reductase and activation of LPL. Its mechanism is different from fibrates but slightly similar to statin. Ananas comosus may serve as the adjuvant for fibrates in the treatment of hyperlipidemia(Xie et al., 2007). S. No 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 Medicinal plants Prunus amygdalus Batsch Boswellia serrata Moringa oleifera Lam Salvia officinalis Aegle marmelos Butea monosperma Asparagus officinalis Linn Capparis spinosa Allium cepa Linn Allium sativum Linn Anethum graveolens Ananas comosus L Bauhinia variegate L. Apium graveolens Abelmoschus esculentus Capparis decidua Cuminum cyminum Linn. Cynodon dactylon Family Rosaceae Burseraceae Moringaceae Lamiaceae Rutaceae Fabaceae Liliaceae. Capparaceae Liliaceae Liliaceae Umbelliferae Bromeliaceae Caesalpinaceae Apiaceae Malvaceae Capparaceae Apiaceae Poaceae Conclusion Medicinal plants have potential to treat hypercholesterolemia and are useful in hypercholesterolemia. Present review indictes that medicinal plants are effective in hypercholesterolemia. Activity of plants is evident from in vitro/ in vivo and clinical trials studies mentioned in this review. Ethics Statement This is a review article and there is no need of approval from ethical committee Conflict of Interest: There is no conflict of interest Disclosure Statement None of the authors have a financial or proprietary interest in the subject matter or materials discussed in the manuscript, including, but not limited to, employment, consultancies, stock ownership, honoraria, and paid expert testimony. References Augusti K, Narayanan A, Pillai L, 2001. Beneficial effects of garlic (Allium sativum Linn) on rats fed with diets containing cholesterol and either of the oil seeds, coconuts or groundnuts. Indian J Exp Biol. 39:660-667. Berryman C, Preston A, Karmally W, 2011. Effects of almond consumption on the reduction of LDL (low density lipoprotein) cholesterol: a discussion of potential mechanisms and future research directions. Nutr Rev. 69:171-185. Bustos C, Hernandez P, 1998. HMG CoA Reductase inhibition by atorvastatin reduces neointimal inflammation in a rabbit model of atherosclerosis. J Am Coll Cardiol. 32: 2057-2064. Chen C, Hsu J, Wang S, 2003. Hibscus sabdariffa extract inhibits the development of atherosclerosis in cholesterol-fed rabbits. J Agric Food Chem. 51: 5472-5477. Devi K, Sivraj A, Kumar P, 2010. Hypolipidemic Effect of Aegle marmelos Leaf Extract in Streptozotocin Induced Diabetic Male Albino Rats. J Adv Pharm Technol Res. 2: 259-265. Reference Teotia et al., 1997 Pandey et al., 2005 Ghasi et al., 2000 Kianbakht et al., 2011 Vijaya et al., 2009 Dixit et al., 2012 Zhu et al., 2011 Eddouks et al., 2005 Sebastian et al., 1979 Augusti et al., 2001 Yazdanparast et al., 2001 Xie et al., 2007 Rajani et al., 2009 Tsi et al., 1995 Sabitha et al., 2011 Purohit et al., 2005 Sarika et al., 2009 Karthik et al., 2011

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Dixit P, Prakash T, Karki R, 2012. Anti-obese activity of Butea monosperma (Lam) bark extract in experimentally induced obese rats, Indian J Exp Biol. 50:476-483. Eddouks M, Lemhadri A, Michel J, 2005. Hypolipidemic activity of aqueous extract of Capparis spinosa L in normal and diabetic rats. J Ethnopharmacol. 98: 345-350. Ghasi S, Nwobodo E, Ofili J, 2000. Hypocholesterolemic effects of crude extract of leaf of Moringa oleifera Lam in high-fat diet fed wistar rats. J. Ethnopharmacol. 69:21-25. Ind J Physiol Pharmacol. 41(4):383-389. Karthik D, Ravikumar S, 2001. A study on the protective effect of Cynodon dactylon leaves extract in diabetic rats, Biomed Environ Sci. 24(2):190-199. Kianbakht S, Abasi B, Perham M, 2011. Antihyperlipidemic effects of Salvia officinalis L. leaf extract in patients with hyperlipidemia: a randomized double, Phytother Res. 25:1849-1853. Kumari K, Augusti K, 2006. Lipid lowering effect of S-methyl cysteine sulfoxide from Allium cepa Linn in high cholesterol diet fed rats, J Ethnopharmacol. 109(3):367-371 Malinow MR, McLaughlin P, Kohler G, 1977. Alfalfa saponins: a family of substances potentially useful for treatment of hypercholesterolemia. Clin Res. 25: 974-979. Pandey R, Singh B, Tripathi Y, 2005. Extract of gum resins of Boswellia serrata L. inhibits lipopolysaccharide induced nitric oxide production in rat macrophages along with hypolipidemic property. Indian J Exp Biol. 43: 509-516. Purohit A, Vyas K, 2005. Hypolipidaemic efficacy of Capparis decidua fruit and shoot extracts in cholesterol fed rabbits. Indian J Exp Biol. 43(10):863-866. Rajani G, Purnima A, 2009. In vitro antioxidant and antihyperlipidemic activities of Bauhinia variegata Linn. Indian J Pharmacol. 41(5): 227232. Saad B, Mahwish A, 2010. Herbal treatment for cardiovascular disease the evidence based therapy. Pak J Pharm Sci. 23:119-124. Sabitha V, Ramachandran S, Naveen KR, Panneerselvam K, 2011. Antidiabetic and antihyperlipidemic potential of Abelmoschus esculentus (L.) Moench. in streptozotocin-induced diabetic rats. J Pharm Bioallied Sci. 3(3):397-402 Salleh M, Runnie I, Roach P, 2002. Inhibition of low-density lipoprotein oxidation and up-regulation of lowdensity lipoprotein receptor in HepG2 cells by tropical plant extract. J Agric Food Chem. 50:36933697. Sarika A, Aarti G, 2009 . Effects of methanolic extract of Cuminum cyminum on total serum cholesterol in ovariectomized rats. Ind J Pharmacol. 41(2): 9293. Sebastian K, Zacharias N, Philip B, 1979. The hypolipidemic effect of onion (Allium cepa Linn) in sucrose fed rabbits. Ind J Physiol Pharmacol. 23:27-30. Sudhahar V, Sekar A, Varalakshmi P, 2006. Role of lupeol and lupeol linolate on lipemic-oxidative stress in experimental hypercholesteromia. Life Sci. 78:1329-1325. Teotia S, Singh M, Pant M, 1997. Effect of Prunus amygdalus seeds on lipid profile. Tsi D, Das N, Tan B, 1995. Effects of aqueous celery (Apium graveolens) extract on lipid parameters of rats fed a high fat diet. Planta Med. 61(1):18-21. Vijaya C, Ramanathan M, Suresh B, 2009. Lipid lowering activity of ethanolic extract of leaves of Aegle marmelos (Linn.) in hyperlipidaemic models of Wistar albino rats. Ind J Exp Biol. 47(3):182-185. Xie W, Wang W, Su H, 2007. Hypolipidemic mechanisms of Ananas comosus L. leaves in mice: Different from fibrates but similar to statins. J Pharmacol Sci. 103:267-274. Yazdanparast R, Alavi M, 2001. Antihyperlipidaemic and antihypercholesterolaemic effects of Anethum graveolens leaves after the removal of furocoumarins. Cytobios, 105:185-91. Zhu X, Zhang W, Pang X, Wang J, Zhao J, Qu W, 2011. Hypolipidemic effect of n-butanol Extract from Asparagus officinalis L. in mice fed a high-fat diet. Phytother Res. 25(8):1119-1124

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