Abstract
The aim of the present study was to evaluate the antidyslipidemic effect of ethanolic extract of Rheum emodi rhizomes and its constituents in Triton-WR-1339 and high-fat diet (HFD)-induced dyslipidemic rats. In preliminary screening, the ethanolic extract showed significant activity in Triton-treated rats. Bioassay-guided fractionation of the ethanolic extract resulted in the identification of four anthraquinone derivatives, viz. chrysophanol, emodin, chrysophanol 8-O-β-d-glucopyranoside and emodin 8-O-β-d-glucopyranoside as active constituents. All these compounds significantly reduced plasma lipid levels. The most active compound emodin showed significant lipid-lowering activity in the HFD-fed model. In addition, these compounds showed significant antioxidant activity. The effect of emodin on enzymes modulating lipid metabolism confirms and supports the efficiency of emodin as a potent antidyslipidemic agent.
Similar content being viewed by others
Abbreviations
- CVD:
-
Cardiovascular diseases
- HDL:
-
High density lipoprotein
- HMG:
-
3-Hydroxy-3-methyl-glutaryl
- LCAT:
-
Lecithin cholesterol acyl transferase
- LDL:
-
Low density lipoprotein
- LPL:
-
Lipoprotein lipase
- PHLA:
-
Post heparin lipolytic activity
- PL:
-
Phospholipids
- TBARS:
-
Thio-barbituric acid reactive species
- TC:
-
Total cholesterol
- TG:
-
Triglycerides
- VLDL:
-
Very low density lipoprotein
References
Kannel WB, Castelli WP, Gordon T, McNamara PM (1971) Serum cholesterol, lipoproteins, and the risk of coronary heart disease. The Framingham study. Ann Intern Med 74:1–12
Sparrow CP, Olszewski J (1993) Cellular oxidation of low density lipoprotein is caused by thiol production in media containing transition metal ions. J Lipid Res 34:1219–1228
Williams KJ, Tabas I (1995) The response-to-retention hypothesis of early atherogenesis. Arterioscler Thromb Vasc Biol 5:551–561
Drechsler M, Megens RT, Van Zandvoort M, Weber C, Soehnlein O (2010) Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation 122:1837–1845
Eisenberg DA (1998) Cholesterol lowering in the management of coronary artery disease: the clinical implications of recent trials. Am J Med 104:2S–5S
Istvan ES, Deisenhofer J (2001) Structural mechanism for statin inhibition of HMG-CoA reductase. Science 292:1160–1164
Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, Gurwitz JH, Chan KA, Goodman MJ, Platt R (2004) Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 292:2585–2590
Barker BJ, Goodenough RR, Falko JM (2003) Fenofibrate monotherapy induced rhabdomyolysis. Diabetes Care 8:2482–2483
Nautiyal BP, Prakash V, Maithani UC, Chauhan RS, Purohit H, Nautiyal MC (2003) Germinability, productivity and economic viability of Rheum emodi Wall. ex Meissn. cultivated at lower altitude. Curr Sci 84:143–148
Kapoor LD (1990) Handbook of Ayurvedic medicinal plants. CRC, Boca Raton, pp 487–497
Babu KS, Srinivas PV, Praveen B, Kishore KS, Murty US, Rao JM (2003) Antimicrobial constituents from the rhizomes of Rheum emodi. Phytochemistry 62:203–207
Agarwal SK, Singh SS, Verma S, Kumar S (2000) Antifungal activity of anthraquinone derivatives from Rheum emodi. J Ethnopharmacol 72:43–46
Huang Q, Lu G, Shen HM, Chung MC, Ong CN (2007) Anti-cancer properties of anthraquinones from rhubarb. Med Res Rev 5:609–630
Suresh Babu K, Tiwari AK, Srinivas PV, Ali AZ, China Raju B, Rao JM (2004) Yeast and mammalian alpha-glucosidase inhibitory constituents from Himalayan rhubarb Rheum emodi Wall. ex Meisson. Bioorg Med Chem Lett 14:3841–3845
Li C, Ye Y (1981) Effect of rhapontin of Rheum hotaoense on lipid and lipoprotein level serum. Acta Pharm Sinica 17:699–702
Verma SC, Singh NP, Sinha AK (2005) Determination and locational variation in the quantity of hydroxyl anthraquinones and their glycosides in rhizomes of Rheum emodi using high-performance liquid chromatography. J Chromatogr A 1097:59–65
Ayyangar NR, Bapat DS, Joshi BS (1961) Anthraquinones and anthrone series: part XXVI– a new synthesis of chrysophanol, rhein, islandicin, emodin and physcion. J Sci Ind Res 20B:493–497
Seo EJ, Ngoc TM, Lee SM, Kim YS, Jung YS (2012) Chrysophanol-8-O-glucoside, an anthraquinone derivative in rhubarb, has antiplatelet and anticoagulant activities. J Pharmacol Sci 118:245–254
Xiang MX, Xu Z, Su HW, Hu J, Yan YJ (2011) Emodin-8-O-β-d-glucoside from Polygonum amplexicaule D. Don var. sinense Forb. promotes proliferation and differentiation of osteoblastic MC3T3-E1 cells. Molecules 16:728–737
Kumar V, Khan MM, Khanna AK, Singh R, Singh S, Chander R, Mahdi F, Mahdi AA, Saxena JK, Singh RK (2008) Hypolipidemic activity of Anthocephalus indicus (kadam) in hyperlipidemic rats. Med Chem Res 17:152–158
Parekh AC, Jung DH (1970) Cholesterol estimation with ferric acetate-uranium acetate and sulfuric acid, ferrous sulfate reagents. Anal Chem 42:1423–1427
Zilversmit DB, Davis AK (1950) Microdetermination of plasma phospholipids by trichloroacetic acid precipitation. J Lab Clin Med 35:155–160
Bucolo G, David H (1973) Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 19:476–482
Shrivastava A, Chaturvedi U, Singh SV, Saxena JK, Bhatia G (2013) Lipid lowering and antioxidant effect of miglitol in triton treated hyperlipidemic and high fat diet induced obese rats. Lipids 48:597–607
Sashidhara KV, Singh SP, Srivastava A, Puri A, Chhonker YS, Bhatta RS, Shah P, Siddiqi MI (2011) Discovery of a new class of HMG-CoA reductase inhibitor from Polyalthia longifolia as potential lipid lowering agent. Eur J Med Chem 46:5206–5211
Nagasaki T, Akanuma Y (1977) A new colorimetric method for determination of plasma lecithin-cholesterol acyltransferase activity. Clin Chem Acta 75:371–375
Wing DR, Robinson DS (1968) Clearing factor lipase in adepose tissue. Biochem J 109:841–849
Mays PA, Felts JM (1968) The functional status of lipoprotein lipase in rat liver. Biochem J 108:483–487
Prasad J, Shrivastava A, Khanna AK, Bhatia G, Awasthi SK, Narender T (2012) Antidyslipidemic and antioxidant activity of the constituents isolated from the leaves of Calophyllum inophyllum. Phytomedicine 19:1245–1249
Rader DJ, Fitzgerald GA (1998) State of the art: atherosclerosis in a limited edition. Nat Med 4:899–900
Wattanapitayakul SK, Bauer JA (2001) Oxidative pathways in cardiovascular disease: roles, mechanisms and therapeutic implications. Pharmacol Therapeut 89:187–206
Sashidhara KV, Kumar M, Sonkar R, Singh BS, Khanna AK, Bhatia G (2012) Indole-based fibrates as potential hypolipidemic and antiobesity agents. J Med Chem 55:2769–2779
Schotz MC, Seanu A, Page IH (1957) Effect of triton on lipoprotein lipase of rat plasma. Am J Physiol 188:399–402
Applebaum DM, Goldberg AP, Pykalisto OJ, Brunzell JD, Hazzard WR (1977) Effect of estrogen on post-heparin lipolytic activity. Selective decline in hepatic triglyceride lipase. J Clin Invest 59:60–608
Jain KS, Kathiravan MK, Somania RS, Shishooc CJ (2007) The biology and chemistry of hyperlipidemia. Bioorg Med Chem 15:4674–4699
Tzeng TF, Lu HJ, Liou SS, Chang CJ, Liu IM (2012) Emodin, a naturally occurring anthraquinone derivative, ameliorates dyslipidemia by activating AMP-activated protein kinase in high-fat-diet-fed rats. Evid Based Complement Alternat Med 2012:781812. doi:10.1155/2012/781812
Acknowledgments
The authors are grateful to the Director CSIR-CDRI, Lucknow for excellent laboratory facilities, SAIF Department of CSIR-CDRI for spectral data and CSIR, New Delhi for providing financial support in the form of senior research fellowships.
Conflict of interest
There is no conflict of interest among the authors.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mishra, S.K., Tiwari, S., Shrivastava, A. et al. Antidyslipidemic effect and antioxidant activity of anthraquinone derivatives from Rheum emodi rhizomes in dyslipidemic rats. J Nat Med 68, 363–371 (2014). https://doi.org/10.1007/s11418-013-0810-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11418-013-0810-z