Butanol Fraction of Rivea ornata Attenuate Endothelial Dysfunction in Rats via Modulation of Cardiovascular Risk Factors


  • Raghavendra Institute of Pharmaceutical Education and Research (RIPER), Department of Pharmaceutical Chemistry, Ananthapuramu, Andhra Pradesh, 515721, India
  • Oil Technological and Pharmaceutical Research Institute (OTPRI), JNTUA College of Engineering, Ananthapuramu, Andhra Pradesh, 515001, India
  • JNTUA, Department of Pharmaceutical Sciences, Ananthapuramu, Andhra Pradesh, 515002, India


Atherosclerosis is caused by vascular inflammation and oxidative stress. Pro-atherogenic effect of hypercholesterolemia caused by impairment of nitric oxide generation due to activated arginase. The study takes up to find the atheroprotective role of polyphenolic fraction of Rivea ornata leaves by using lipid emulsion induced atherosclerosis in rat model. The study carried out by studying atherogenic markers in the serum (lipid profiles, C-reactive protein), vascular tissue (myeloperoxidase, arginase, hydroxyproline, lipid peroxidation) and atheroprotective factors in the serum (paraoxonase, nitric oxide), and in the vascular tissue (thiol levels, endogenous antioxidants) after feeding the rats with lipid emulsion for 12 weeks. Treatment of polyphenolic rich butanol fraction is able to correct the imbalance of atherogenic and antiatherogenic factors induced by lipid emulsion feeding. Butanol fraction at the dose of 400 mg/kg significantly increases high density lipoprotein, paraoxonase, nitric oxide, tissue thiol levels, endogenous antioxidants and decreases total triglycerides, total cholesterol, very low-density lipoprotein, low density lipoprotein, myeloperoxidase, arginase, hydroxyproline, lipid peroxidation. The atheroprotection reflected in histopathology studies also. Lipid emulsion associated foam cells formation is inhibited by butanol fraction. These all are due to the presence of gallic acid in polyphenol rich butanol fraction is responsible for the underlying mechanism of atheroprotection.


Butanol Fraction, Cardiac Rick Factors, High Performance Liquid Chromatography Analysis, Inflammation Markers, Lipid Emulsion Induced Atherosclerosis, Lipid Profiles

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Diao SL, Sun JW, Ma BX, Li XM, Wang D. Influence of crocetin on high-cholesterol diet induced atherosclerosis in rats via anti-oxidant activity together with inhibition of inflammatory response and p38 MAPK signaling pathway. Saudi J Biol Sci. 2018; 25(3):493–99. https://doi.org/10.1016/j. sjbs.2016.11.005. PMid:29692651. PMCid:PMC5911641

Abrams J. Clinical practice. Chronic stable angina. N Engl J Med. 2005; 352(24):2524-33. https://doi.org/10.1056/ NEJMcp042317. PMid:15958808

Tan ST, Scott W, Panoulas V, Sehmi J, Zhang W, Scott J, Elliott P, Chambers J, Kooner JS. Coronary heart disease in Indian Asians. Glob Cardiol Sci Pract. 2014; 2014(1):13– 23. https://doi.org/10.5339/gcsp.2014.4. PMid:25054115. PMCid:PMC4104373

Gao J, Liu C, Zhang H, Sun Z, Wang R. Myricitrin exhibits anti-atherosclerotic and anti-hyperlipidemic effects in diet-induced hypercholesterolemic rats. AMB Express. 2019; 9(1):204. https://doi.org/10.1186/s13568-019-0924-0. PMid:31865448 PMCid:PMC6925610

Yang Z, Ming XF. Arginase: the emerging therapeutic target for vascular oxidative stress and inflammation. Front Immunol. 2013; 4:149. https://doi.org/10.3389/fimmu.2013.00149

Pernow J, Jung C. Arginase as a potential target in the treatment of cardiovascular disease: reversal of arginine steal? Cardiovasc Res. 2013; 98(3):334–43. https://doi. org/10.1093/cvr/cvt036. PMid:23417041

Minozzo BR, Fernandes D, Beltrame FL. Phenolic compounds as arginase inhibitors: New insights regarding endothelial dysfunction treatment. Planta Med. 2018; 84(5):277–95. https://doi.org/10.1055/s-0044-100398. PMid:29342480

Kirtikar KR, Basu BD. Indian Medicinal Plants - Volume III. Second Edition, Dehra Dun: International book distributors; 2008.

Vaishali JS, Piyush MP. Bergenin-An active constituent of Rivea ornata Roxb. and its antioxidant property. Int J Pharmacogn. 2017; 4(9):309–19.

Sholapur HN, Patil BM. Effect of Moringa oleifera bark extracts on dexamethasone-induced insulin resistance in rats. Drug Res (Stuttg). 2013t; 63(10):527–31. https://doi. org/10.1055/s-0033-1347238. PMid:23780503

Baba SA, Malik SA. Determination of total phenolic and flavonoid content, antimicrobial and antioxidant activity of a root extract of Arisaema jacquemontii Blume. J. Taibah Univ. Sci. 2015; 9:4, 449–54. https://doi.org/10.1016/j. jtusci.2014.11.001

Siddiqui R, Ahamed HN, Yusuff I. Bisflavonoids fraction from Araucaria bidwilli Hook., reverses hyperlipidemia induced atherosclerosis in high-fat diet induced hyperlipidemia. Futur J Pharm Sci. 2020; 6:89. https://doi.org/10.1186/ s43094-020-00109-y

Kaya B, Menemen Y, Saltan FZ. Flavonoid compounds identified in Alchemilla L. species collected in the north-eastern Black Sea region of Turkey. Afr J Tradit Complement Altern Med. 2012; 9(3):418–25. https://doi.org/10.4314/ajtcam. v9i3.18. PMid:23983376. PMCid:PMC3746660

Konan KM, Mamyrbekova-Bekro JA, Bakalara N, Virieux D, Pirat JL, Bekro YA. HPLC analysis and cytotoxicity of n-butanol extract from glyphaea brevis roots against C6 glioma cells. Sci Pharm. 2013; 82(1):171–6. https:// doi.org/10.3797/scipharm.1307-08. PMid:24634849. PMCid:PMC3951227

Maithili V, Dhanabal SP, Mahendran S, Vadivelan R. Antidiabetic activity of ethanolic extract of tubers of Dioscorea alata in alloxan induced diabetic rats. Indian J Pharmacol. 2011; 43(4):455–9. https://doi.org/10.4103/0253-7613.83121. PMid:21845005. PMCid:PMC3153713

Gou SH, Liu BJ, Han XF, Wang L, Zhong C, Liang S, et al. Anti-atherosclerotic effect of Fermentum rubrum and Gynostemma pentaphyllum mixture in high-fat emulsion- and vitamin D3-induced atherosclerotic rats. J Chin Med Assoc. 2018; 81(5):398–408. https://doi.org/10.1016/j. jcma.2017.08.018. PMid:29107606

Subramani C, Rajakkannu A, Rathinam A, Gaidhani S, Raju I, Kartar Singh DV. Anti-atherosclerotic activity of root bark of Premna integrifolia Linn. in high fat diet induced atherosclerosis model rats. J Pharm Anal. 2017; 7(2):123–8. https://doi.org/10.1016/j.jpha.2016.12.002. PMid:29404027. PMCid:PMC5686870

Mehdi MM, Rizvi SI. Plasma protein hydroperoxides during aging in humans: correlation with paraoxonase 1 (PON1) arylesterase activity and plasma total thiols. Arch Med Res. 2013; 44(2):136–41. https://doi.org/10.1016/j.arcmed. 2013.01.003. PMid:23376056

Solanki YB, Jain SM. Antihyperlipidemic activity of Clitoria ternatea and Vigna mungo in rats. Pharm Biol. 2010; 48(8):915–23. https://doi.org/10.3109/13880200903406147. PMid:20673179

Chithra V, Leelamma S. Hypolipidemic effect of coriander seeds (Coriandrum sativum): Mechanism of action. Plant Foods Hum Nutr. 1997; 51(2):167–72. https://doi. org/10.1023/A:1007975430328. PMid:9527351

Arya DS, Arora S, Malik S, Nepal S, Kumari S, Ojha S. Effect of Piper betle on cardiac function, marker enzymes, and oxidative stress in isoproterenol-induced cardiotoxicity in rats. Toxicol Mech Methods. 2010; 20(9):564–71. https:// doi.org/10.3109/15376516.2010.514962. PMid:20846025

Hedayati M, Niazmand S, Hosseini M, Baghcheghi Y, Beheshti F, Niazmand S. Vitamin E improved redox homeostasis in heart and aorta of hypothyroid rats. Endocr Regul. 2017; 51(4):205–12. https://doi.org/10.1515/enr-2017- 0021. PMid:29232192

Akinyemi AJ, Onyebueke N, Faboya OA, Onikanni SA, Fadaka A, Olayide I. Curcumin inhibits adenosine deaminase and arginase activities in cadmium-induced renal toxicity in rat kidney. J Food Drug Anal. 2017; 25(2):438–46. https://doi.org/10.1016/j.jfda.2016.06.004. PMid:28911688

Boyapally R, Pulivendala G, Bale S, Godugu C. Niclosamide alleviates pulmonary fibrosis in vitro and in vivo by attenuation of epithelial-to-mesenchymal transition, matrix proteins and Wnt/?-catenin signaling: A drug repurposing study. Life Sci. 2019; 220:8–20. https://doi.org/10.1016/j. lfs.2018.12.061. PMid:30611787

Thippeswamy BS, Mahendran S, Biradar MI, Raj P, Srivastava K, et al. Protective effect of embelin against acetic acid induced ulcerative colitis in rats. Eur J Pharmacol. 2011; 654(1):100–5. https://doi.org/10.1016/j.ejphar.2010.12.012. PMid:21185828

Bale S, Sunkoju M, Reddy SS, Swamy V, Godugu C. Oropharyngeal aspiration of bleomycin: An alternative experimental model of pulmonary fibrosis developed in Swiss mice. Indian J Pharmacol. 2016; 48(6):643–8. https:// doi.org/10.4103/0253-7613.194859. PMid:28066100. PMCid:PMC5155463

Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004; 109(23 Suppl 1):III27–32. https://doi.org/10.1161/01.CIR.0000131515.03336.f8

Isolation of prunin from Bauhinia variegata and its antioxidant activity in rats fed an atherogenic diet. Nat Prod Commun. 2020; 15(10). https://doi. org/10.1177/1934578X20967875

Huseini HF, Anvari MS, Khoob YT, Rabbani S, Sharifi F, Arzaghi SM, Fakhrzadeh H. Anti-hyperlipidemic and anti-atherosclerotic effects of Pinus eldarica Medw. nut in hypercholesterolemic rabbits. Daru. 2015; 23(1):32. https:// doi.org/10.1186/s40199-015-0114-9. PMid:26054525. PMCid:PMC4483207

Akowuah GA, Sadikun A, Mariam A. Flavonoid identification and hypoglycaemic studies of the butanol fraction from gynura procumbens. Pharmaceutical Biology. 2008; 40(6):405–10. https://doi.org/10.1076/phbi.40.6.405.8440

Behl T, Bungau S, Kumar K, Zengin G, Khan F, Kumar A, et al. Pleotropic effects of polyphenols in cardiovascular system. Biomed Pharmacother. 2020; 130:110714. https://doi. org/10.1016/j.biopha.2020.110714. PMid:34321158

Hsu CL, Yen GC. Effect of gallic acid on high fat diet-induced dyslipidaemia, hepatosteatosis and oxidative stress in rats. Br J Nutr. 2007; 98(4):727–35. https://doi.org/10.1017/ S000711450774686X. PMid:17475086

Wu Y, Wang Y, Liu X, Jiang L, Guli A, Sailike J, et al. Ziziphora clinopodioides flavonoids based on network pharmacology attenuates atherosclerosis in rats induced by high-fat emulsion combined with vitamin D3 by downregulating VEGF/AKT/NF-?B signaling pathway. Biomed Pharmacother. 2020; 129:110399. https://doi.org/10.1016/j. biopha.2020.110399. PMid:32768933

Saravanan M, Pandikumar P, Prakash Babu N, Ignacimuthu S. Antihyperlipidemic activity of Ichnocarpus frutescens in triton WR-1339-induced and high-fat diet animals. Pharm Biol. 2011; 49(10):1074–81. https://doi.org/10.3109/138802 09.2011.565477. PMid:21591834

Munshi RP, Joshi SG, Rane BN. Development of an experimental diet model in rats to study hyperlipidemia and insulin resistance, markers for coronary heart disease. Indian J Pharmacol. 2014; 46(3):270–6. https:// doi.org/10.4103/0253-7613.132156. PMid:24987172. PMCid:PMC4071702

Variya BC, Bakrania AK, Chen Y, Han J, Patel SS. Suppression of abdominal fat and anti-hyperlipidemic potential of Emblica officinalis: Upregulation of PPARs and identification of active moiety. Biomed Pharmacother. 2018; 108:1274–81. https://doi.org/10.1016/j.biopha.2018.09.158. PMid:30372828

Zhu Z, Lin Z, Jiang H, Jiang Y, Zhao M, Liu X. Hypolipidemic effect of Youcha in hyperlipidemia rats induced by high-fat diet. Food Funct. 2017; 8(4):1680–7. https://doi.org/10.1039/C7FO00089H. PMid:28379241

Sandhya VG, Rajamohan T. Comparative evaluation of the hypolipidemic effects of coconut water and lovastatin in rats fed fat-cholesterol enriched diet. Food Chem Toxicol. 2008; 46(12):3586–92. https://doi.org/10.1016/j.fct.2008.08.030. PMid:18809454

Balzan S, Hernandes A, Reichert CL, Donaduzzi C, Pires VA, Gasparotto A Jr, et al. Lipid-lowering effects of standardized extracts of Ilex paraguariensis in high-fat-diet rats. Fitoterapia. 2013; 86:115–22. https://doi.org/10.1016/j. fitote.2013.02.008. PMid:23422228

Huang Y, Wu Z, Riwanto M, Gao S, Levison BS, Gu X, et al. Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex. J Clin Invest. 2013; 123(9):3815–28. https://doi.org/10.1172/JCI67478. PMid:23908111. PMCid:PMC3754253

Nicholls SJ, Hazen SL. Myeloperoxidase, modified lipoproteins, and atherogenesis. J Lipid Res. 2009; 50 Suppl(Suppl):S346–51. https://doi.org/10.1194/jlr. R800086-JLR200. PMid:19091698. PMCid:PMC2674690

Harisa GI, Attia SM, Zoheir KM, Alanazi FK. Chitosan treatment abrogates hypercholesterolemia-induced erythrocyte’s arginase activation. Saudi Pharm J. 2017; 25(1):120–7. https://doi.org/10.1016/j.jsps.2016.05.007. PMid:28223872. PMCid:PMC5310152

Lü L, Zhang D, Sun B, Hu Y, Yan M, Liu K, et al. Apocynum leaf extract inhibits the progress of atherosclerosis in rats via the AMPK/mTOR pathway. Pharmazie. 2017; 72(1):41–8.

Sarma R, Kumari S, Elancheran R, Deori M, Devi R. Polyphenol rich extract of Garcinia pedunculata fruit attenuates the hyperlipidemia induced by high fat diet. Front Pharmacol. 2016; 7:294. https://doi.org/10.3389/ fphar.2016.00294

Kilany OE, Abdelrazek HMA, Aldayel TS, Abdo S, Mahmoud MMA. Anti-obesity potential of Moringa olifera seed extract and lycopene on high fat diet induced obesity in male Sprauge Dawely rats. Saudi J Biol Sci. 2020; 27(10):2733–46. https://doi.org/10.1016/j.sjbs.2020.06.026. PMid:32994733. PMCid:PMC7499387


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