Official publication of Rawalpindi Medical University
Anti-Hyperlipidemic Effect of Zinc complex of Betulinic acid in High Fat Diet- Induced Hyperlipidemia

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Zinc, Betulinic acid, High Fat Diet, Hyperlipidemia, Simvastatin

How to Cite

Tayyab M, Jehangir A, Ayub F, Ijaz N, Ahmed` S, Munir A. Anti-Hyperlipidemic Effect of Zinc complex of Betulinic acid in High Fat Diet- Induced Hyperlipidemia. JRMC [Internet]. 2023 Apr. 1 [cited 2023 Jun. 5];27(1). Available from:


Background: Hyperlipidemia is considered a modifiable risk factor for cardiovascular disease and atherosclerosis. Drugs of first choice, Statins, despite being well tolerable, are accompanied by many adverse effects. To tackle the shortcomings of standard drugs, there is dire demand to make an agent which equates to a better response. This study evaluated the anti-hyperlipidemic and comparative effects of Zinc complex of Betulinic acid (Zn+BA) with simvastatin (SIM), on high-fat diet-induced hyperlipidemia in rats, and the safety profile of the two treatments was also assessed.

Methodology: Hyperlipidemia was induced by giving a high-fat diet. BA +Zn 10 mg/kg and SIM 20 mg/kg were given orally for four weeks. On the final day terminal sampling was done and serum lipid profile (TG, TC, LDL, HDL) and hepatic enzymes (ALT) for assessing hepatotoxicity were estimated. Results: Our results showed that BA+Zn significantly increased HDL levels and significantly reduced serum TC, TG, and LDL (p<0.001) as compared to Simvastatin. Correspondingly serum ALT levels also showed significant reduction (p<0.001) in comparison with Simvastatin.

Conclusion: Our study suggests that BA+Zn effectively attenuates high-fat diet-induced hyperlipidemia while preserving hepatic function and could serve as a better alternative to simvastatin in treating hyperlipidemia.


Sarker S, Haque MI, Sujan KM, Talukder MI, Miah MA. Curcumin attenuates butter fat induced hyperlipidemia in mice. J Bangladesh Agric Univ [Internet]. 2019;17(2):220–5. Available from:

Song D, Jiang J. Hypolipidemic components from medicine food homology species used in china: pharmacological and health effects. Arch Med Res [Internet]. 2017;48:569–81. Available from:

Bhatnagar P, Wickramasinghe K, Williams J, Rayner M, Townsend N. The epidemiology of cardiovascular disease in the UK 2014. Heart [Internet]. 2015;101:1182–9. Available from: doi: 10.1136/heartjnl-2015-307516

Shahid SU, Sarwar S. The abnormal lipid profile in obesity and coronary heart disease (CHD) in Pakistani subjects. Lipids Health Dis [Internet]. 2020;19:1–7. Available from:

Babelova A, Sedding DG, Brandes RP. Anti-atherosclerotic mechanisms of statin therapy. Curr Opin Pharmacol [Internet]. 2013;13:260–4. Available from:

Mehrpooya M, Larki-Harchegani A, Ahmadimoghaddam D, Kalvandi M, Mohammadi Y, Javad MT, et al. Evaluation of the Effect of Education Provided by Pharmacists on Hyperlipidemic Patient’s Adherence to Medications and Blood Level of Lipids. J Appl Pharm Sci [Internet]. 2018;8:29–33. Available from: doi: 10.7324/JAPS.2018.8105

Crisan E, Patil VK. Neuromuscular complications of statin therapy. Curr Neurol Neurosci Rep [Internet]. 2020;20(10):1–7. Available from:

Park JY, Rha S-W, Choi B, Choi JW, Ryu SK, Kim S, et al. Impact of low dose atorvastatin on development of new-onset diabetes mellitus in Asian population: three-year clinical outcomes. Int J Cardiol [Internet]. 2015;184:502–6. Available from:

Björnsson ES. Hepatotoxicity of statins and other lipid-lowering agents. Liver Int [Internet]. 2017 Feb 1;37(2):173–8. Available from:

Silva FSG, Oliveira PJ, Duarte MF. Oleanolic, Ursolic, and Betulinic Acids as Food Supplements or Pharmaceutical Agents for Type 2 Diabetes: Promise or Illusion? J Agric Food Chem [Internet]. 2016;64(15):2991–3008. Available from:

Ajala-Lawal RA, Aliyu NO, Ajiboye TO. Betulinic acid improves insulin sensitivity, hyperglycemia, inflammation and oxidative stress in metabolic syndrome rats via PI3K/Akt pathways. Arch Physiol Biochem [Internet]. 2018;0(0):1–9. Available from:

Khan MF, Nahar N, Rashid R Bin, Chowdhury A, Rashid MA. Computational investigations of physicochemical, pharmacokinetic, toxicological properties and molecular docking of betulinic acid, a constituent of Corypha taliera (Roxb.) with Phospholipase A2 (PLA2). BMC Complement Altern Med. 2018;18(1):1–15.

Shi Y, Zou Y, Shen Z, Xiong Y, Zhang W, Liu C, et al. Trace elements, PPARs, and metabolic syndrome. Int J Mol Sci [Internet]. 2020;21(7):2612. Available from:

Olechnowicz J, Tinkov A, Skalny A, Suliburska J. Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci [Internet]. 2018;68(1):19–31. Available from:

Pandurangan M, Jin BY, Kim DH. ZnO Nanoparticles upregulates adipocyte differentiation in 3T3-L1 cells. Biol Trace Elem Res [Internet]. 2016;170:201–7. Available from:

Zainub A, Ayub F, Jehangir A, Inam T, Lodhi S, Ayub S. Comparative Study of Betulinic Acid Versus Simvastatin on Total Cholesterol and HDL in Hyperlipidemic Model. Biomedica. 2018;34(4):248.

Speakman JR. Use of high-fat diets to study rodent obesity as a model of human obesity. Int J Obes [Internet]. 2019;43(8):1491–2. Available from:

Campolongo G, Riccioni CV, Raparelli V, Spoletini I, Marazzi G, Vitale C, et al. The combination of nutraceutical and simvastatin enhances the effect of simvastatin alone in normalising lipid profile without side effects in patients with ischemic heart disease. IJC Metab Endocr [Internet]. 2016;11:3–6. Available from:

Sadri H, Larki NN, Kolahian S. Hypoglycemic and Hypolipidemic Effects of Leucine, Zinc, and Chromium, Alone and in Combination, in Rats with Type 2 Diabetes. Biol Trace Elem Res [Internet]. 2017;180(2):246–54. Available from:

Zhou X, Ren F, Wei H, Liu L, Shen T, Xu S, et al. Combination of berberine and evodiamine inhibits intestinal cholesterol absorption in high fat diet induced hyperlipidemic rats. Lipids Health Dis. 2017;16:239.

OECD TN. 423: Acute Oral toxicity–Acute Toxic Class Method. OECD Guidel Test Chem Sect. 2001;4.

Chrysant SG. New onset diabetes mellitus induced by statins: current evidence. Postgrad Med [Internet]. 2017 May 19;129(4):430–5. Available from:

Ramkumar S, Raghunath A, Raghunath S. Statin Therapy: Review of Safety and Potential Side Effects. Acta Cardiol Sin [Internet]. 2016 Nov;32(6):631–9. Available from:

Adhyaru BB, Jacobson TA. New Cholesterol Guidelines for the Management of Atherosclerotic Cardiovascular Disease Risk: A Comparison of the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines with the 2014 National Lipid Association Recommendation. Endocrinol Metab Clin [Internet]. 2016 Mar 1;45(1):17–37. Available from:

Ahangarpour A, Shabani R, Farbood Y. The effect of betulinic acid on leptin, adiponectin, hepatic enzyme levels and lipid profiles in streptozotocin-nicotinamide-induced diabetic mice. Res Pharm Sci [Internet]. 2018;13(2):142–8. Available from: doi: 10.4103/1735-5362.223796

Naito Y, Yoshikawa Y, Yoshizawa K, Takenouchi A, Yasui H. Beneficial effect of bis(hinokitiolato)Zn complex on high-fat diet-induced lipid accumulation in mouse liver and kidney. In Vivo (Brooklyn) [Internet]. 2017;31(6):1145–51. Available from: doi: 10.21873/invivo.11181

Wei CC, Luo Z, Hogstrand C, Xu YH, Wu LX, Chen GH, et al. Zinc reduces hepatic lipid deposition and activates lipophagy via Zn2+/MTF-1/PPARa and Ca2+/CaMKKb/AMPK pathways. FASEB J. 2018;32(12):6666–80.

Yoon JJ, Lee YJ, Han BH, Choi ES, Kho MC, Park JH, et al. Protective effect of betulinic acid on early atherosclerosis in diabetic apolipoprotein-E gene knockout mice. Eur J Pharmacol [Internet]. 2017;796:224–32. Available from:

Choi S, Liu X, Pan Z. Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases. Acta Pharmacol Sin [Internet]. 2018;39(7):1120–32. Available from:

Asbaghi O, Sadeghian M, Fouladvand F, Panahande B, Nasiri M, Khodadost M, et al. Effects of zinc supplementation on lipid profile in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis [Internet]. 2020;30(8):1260–71. Available from:

Oriakhi K, Uadia PO, Shaheen F, Jahan H, Ibeji CU, Iqbal CM. Isolation, characterization, and hepatoprotective properties of betulinic acid and ricinine from Tetracarpidium conophorum seeds (Euphorbiaceae). J Food Biochem [Internet]. 2021;45(3):e13288. Available from:

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Copyright (c) 2023 Mehwish Tayyab, Adnan Jehangir, Farhana Ayub, Nimra Ijaz, Sameer Ahmed, Attiya Munir