Author(s): Muthaiyan Revathi, Ganesan Jagadeesan

Email(s): ,

DOI: 10.52711/0974-360X.2022.00199   

Address: Muthaiyan Revathi1, Ganesan Jagadeesan2*
1Ph.D., Research Scholar, Department of Zoology, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu, 608002, India.
2Professor and Head, Department of Zoology, Annamalai University, Annamalai Nagar, Chidambaram, Tamil Nadu, 608002, India.
*Corresponding Author

Published In:   Volume - 15,      Issue - 3,     Year - 2022

Mercuric is considered as a highly dangerous, universal environmental toxin and it promotes diverse pathophysiology in many organs appended liver disorders through oxidative stress. Hence, the existing investigation was organized to determine the ameliorative defensive character of betulinic acid and rotundic acid in adult albino male rats hepatotoxicity induced by Mercuric chloride. HgCl2 was given orally for 1.29 mg/kg of body weight of Albino wistar rats for 7 days and betulinic acid and rotundic acid (5mg/kg body weight) was dosed for another 7 days on intoxicated rats. Betulinic acid and rotundic acid treatment significantly improved the defense system through enhancing their enzymatic antioxidant properties [superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)], glutathione (GSH) level and decreased the elevated lipid peroxidation (LPO) content in toxicated rats. Histological alterations of liver tissues induced by HgCl2 were managed by infliction of betulinic acid and rotundic acid. The observed results from the present experiment proposed that betulinic acid and rotundic acid effectively suppress and terminates hepatotoxicity induced through HgCl2 by reliving oxidative stress and liver damage.

Cite this article:
Muthaiyan Revathi, Ganesan Jagadeesan. Hepato-Protective effect of Betulinic acid and Rotundic acid on Mercuric Chloride Intoxicated Albino Wistar Rats. Research Journal of Pharmacy and Technology. 2022; 15(3):1189-5. doi: 10.52711/0974-360X.2022.00199

Muthaiyan Revathi, Ganesan Jagadeesan. Hepato-Protective effect of Betulinic acid and Rotundic acid on Mercuric Chloride Intoxicated Albino Wistar Rats. Research Journal of Pharmacy and Technology. 2022; 15(3):1189-5. doi: 10.52711/0974-360X.2022.00199   Available on:

1.    L. Officioso, Panzella, F. Tortora, M.L. Alfieri, A. Napolitano, C. Manna, Comparative  analysis of the effects of olive oil hydroxytyrosol and its 5-S-lipoyl conjugate in protecting human erythrocytes from mercury toxicity, Oxid. Med. Cell. Longev. 2018.
2.    H. Zhang, X. Tan, D. Yang, J. Lu, B. Liu, R. Baiyun, Z. Zhang, Dietary luteolin attenuates chronic liver injury induced by mercuric chloride via the Nrf2/Nf-κB/P53 signaling pathway in rats, Oncotarget. 2017; 8 (25): 40982.
3.    M. Uzunhisarcikli, A. Aslanturk, S. Kalender, F.G. Apaydin, H. Bas, Mercuric chloride induced hepatotoxic and hematologic changes in rats: the protective effects of sodium selenite and vitamin E, Toxicol. Ind. Health. 2016; 1651–1662.
4.    Bharathi E, Jagadeesan G, Vijayakumar M. Hepato-ameliorative effect of hesperidin and ellagic acid on mercuric chloride intoxicated rats, Biomed Aging Pathol. 2014; 4: 17-21.
5.    D. Joshi, S.K. Srivastav, S. Belemkar, V.A. Dixit, Zingiber officinale and 6-gingerol alleviate liver and kidney dysfunctions and oxidative stress induced by mercuric chloride in male rats: a protective approach, Biomed. Pharmacother. 2017; 91: 645–655.
6.    M. Ekambaram, K.A. Ramalingam, A. Balasubramanian, Effect of solanum trilobatum linn on mercury-induced hepatotoxicity in Swiss albino mice, J. Drug. Deliv. Ther. 2012; 2(6): 68–70.
7.    P. Malini, G. Kanchana, M. Rajadurai, Antidiabetic efficacy of ellagic acid in streptozotoc in induced diabetes mellitus in albino wistar rats, Asian J. Pharm. Clin. Res. 2011; 4(3): 124–8.
8.    S. Kumar, N. Dhankhar, V. Kar, M. Shrivastava, S. Shrivastava, Myocardial injury provoked by cyclophosphamide, protective aspect of hesperidin in rats, Int. J. Res. Pharm. Biomed. Sci. 2011; 2(3): 1288–96.
9.    S.A. Bashandy, I.M. Alhazza, G.E. El-Desoky, Z.A. Al-Othman, Hepatoprotective and hypolipidemic effects of Spirulina platensis in rats administered mercuric chloride, Afr. J. Pharm. Pharmacol. 2011; 5(2): 175–82.
10.    R. Agarwal, S.K. Goel, R. Chandra, J.R. Behari, Role of vitamin E in preventing acute mercury toxicity in rat, Environ. Toxicol. Pharmacol. 2010; 29 (1): 70–78.
11.    J.P. Rooney, The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury, Toxicology. 2007; 234 (3): 145–156.
12.    A.E.A. Moneim, The neuroprotective effect of berberine in mercury-induced neurotoxicity in rats, Metab. Brain Dis. 2015; 30 (4): 935–942.
13.    D. Joshi, D.K. Mittal, S. Shukla, A.K. Srivastav, S.K. Srivastav, N-acetyl cysteine andselenium protects mercuric chloride-induced oxidative stress and antioxidant defensesystem in liver and kidney of rats: a histopathological approach, J. Trace Elem. Med. Biol. 2014; 28 (2): 218–226.
14.    C. Caglayan, F.M. Kandemir, S. Yildirim, S. Kucukler, G. Eser, Rutin protects mercuric chloride‐induced nephrotoxicity via targeting of aquaporin 1 level, oxidative stress, apoptosis and inflammation in rats, J. Trace Elem. Med. Biol. 2019; 54: 69–78.
15.    M.A. Boujbiha, G.B. Salah, A.B. Feleh, M. Saoudi, H. Kamoun, A. Bousslema, A. Ommezzine, K. Said, F. Fakhfakh, A. El Feki, Hematotoxicity and genotoxicity of mercuric chloride following subchronic exposure through drinking water in male rats, Biol. Trace Elem. Res. 2012; 148 (1): 76–82.
16.    D. Yang, X. Tan, Z. Lv, B. Liu, R. Baiyun, J. Lu, Z. Zhang, Regulation of Sirt1/Nrf2/TNF-α signaling pathway by luteolin is critical to attenuate acute mercuric chloride exposure induced hepatotoxicity, Sci. Rep. 2016; 6: 37157.
17.    Caglayana, F. M. Kandemir, E. Darendelioglu, S. Yıldırım, S. Kucuklerb, M. B. Dortbudak, Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis, J. Trace Elem. Med. Biol. 2019; 56: 60–68.
18.    T. Preeti, K. P. Rakesh Estimation of Total Phenolics and Flavonoids and Antioxidant Potential of Ashwagandharishta Prepared by Traditional and Modern Methods. Asian J. Pharm. Ana. 2014; 4(1) 05-10.
19.    Amit Roy, Dayananda Bhoumik, Ram Kumar Sahu, Jaya Dwivedi. Phytochemical Screening and Antioxidant Activity of Sesbania grandiflora Leaves Extracts. Asian J. Res. Pharm. Sci. 2014; 4(1) 16-21.
20.    Ahmad Zubaidi Bin A. Latif, Mainul Haque, C. Shanmugasundaram, U.S. Mahadeva Rao. Clinical Study of Preventive Potentials of Consumption of Buah naga [Cactaceae] Against Paracetamol–Induced Hepatotoxicity as well as the Other Associated Biological Effects. Asian J. Res. Pharm. Sci. 2012; 2(1): 16-23.
21.    Y. Wan, Y.L. Wu, L.H. Lian, W.X. Xie, X. Li, B.Q. OuYang, T. Bai, Q. Li, N. Yang, J.X. Nan, The anti-fibrotic effect of betulinic acid is mediated through the inhibition of NF-κB nuclear protein translocation, Cheml. Biol. Interact. 2012; 195: 215–223.
22.    S. Fulda, Betulinic acid: a natural product with anticancer activity, Mol. Nutr. Food Res. 2009; 53: 216–220.
23.    R.H. Cichewicz, S.A. Kouzi, Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection, Med. Res. Rev. 2004; 24: 90–114.
24.    J. Yi, R. Zhu, J. Wu, J. Wu, W. Xia, L. Zhu, W. Jiang, S. Xiang, Z. Tan, In vivo protective effect of betulinic acid on dexamethasone induced thymocyte apoptosis by reducing oxidative stress, Pharmacol. Rep. 2016; 68: 95–100.
25.    H. Sun, X.Q. Zhang, Y. Cai, W.L. Han, Y. Wang, W.C. Ye, Study on chemical constituents of Ilex rotunda Thunb, Chem. Indus. Forest Prod. 2009; 295: 111–114.
26.    H. Haraguchi, S. Kataoka, S. Okamoto, M. Hanafi, K. Shibata, Antimicrobial triterpenes from Ilex integra and the mechanism of antifungal action, Phytother. Res. 1999; 13: 151.
27.    W.M. Zhao, J.L. Wolfender, K. Hostettmann, K.F. Cheng, R.S. Xu, G.W. Qin, Triterpenes and triterpenoid saponins from Mussaenda pubescens, Phytochemistry. 1997; 45: 1073–1078.
28.    J. Bhattacharyya, M.D. Almeida, Isolation of the constituents of the root-bark of Guettarda platypoda, J. Nat. Prod. 1985; 48: 148.
29.    Z.H. Li, H.S. Zhang, F.L. Xu, Z.Y. Wu, Triterpene acids from the leaves of Planchonella duclitan (Blanco) Bakhuizan, J. Chin. Chem. Soc. 2005; 52: 1275–1280.
30.    H. Saimaru, Y. Orihara, P. Tahsakul, Y.H. Kang, M. Shibuya, Y. Ebizuka, Production of triterpene acids by cell suspension cultures of Olea europaea, Chem. Pharm. Bull. 2007; 55: 784–788.
31.    W.Z. Ma, T.J. Ling, Y.H. Zhang, L.D. Lin, Chemical Constituents from Nauclea officinalis, J. Trop. Subtrop. Bot. 2004; 13: 167–170.
32.    M. K. Parvez, M. S. Al-Dosari, A. H. Arbab et al., The in vitro and in vivo anti-hepatotoxic, anti-hepatitis B virus and hepatic CYP450 modulating potential of Cyperus rotundus in vitro and in vivo anti-hepatotoxic, anti-hepatitis B virus, Saudi Pharm. J. 2019; 2: 1319-0164.
33.    R. Xu, Studied on the Chemical Components and Antitumor Activity of Ilex rotunda Thunb, Ph.D. Thesis, Guangzhou University of Chinese Medicine, 2009. In Chinese. 30.
34.    G. Q. Liu, (2010); CHN 200810198190.7.
35.    Y.F. He, M.L. Nan, J.M. Sun, Z.J. Meng, W. Li, M. Zhang, Design, synthesis and cytotoxicity of cell death mechanism of rotundic acid derivatives, Bioorg. Med. Chem. Lett. 2013; 23: 2543–2547.
36.    M. Manju, G. Jagadeesan, In vivo hepatoprotective effect of caffeic acid on mercuric chloride-induced biochemical changes in albino wistar rats, Asian J. Pharm. Clin. Res. 2019; 12 (4): 119-124.
37.    W.G. Nichens, B. Samuelson, Fomulation of malondialdehyde from phospho-lipid arachidouate during microsomal lipid peroxidation, Eur. J. Biochem. 1968; 6: 126–30.
38.    E. Beutler, B.M. Kelley, The effect of disodium nitrate on RBC glutathione. Experintia. 1963; 29: 97-101.
39.    P. Kakkar, B. Das, P.N. Viswanathan, A modified spectrophotometric assay of SOD, Indian J. Biochem. Biophys. 1984; 21; 131–2.
40.    K.A. Sinha, Colorimetric assay of catalase, Anal. Biochem. 1972; 47: 389–94.
41.    J.J. Rotruck, A.L. Pope, H.E. Gauther, A.B. Swanson, D.G. Hateman, W.G. Hoekstra, Selenium biochemical role as a component at glutathione peroxidase, Science, 1973; 179: 588–90.
42.    Gurr, E.  Methods  for  analytical histology and histochemistry. Leonard Hill (Books) Ltd. London, 1959.
43.    B.D. Duncan, Duncan’s multiple range test for correlated and hetroscedastic mean, Biometics. 1957; 13: 354–64.
44.    R. Selvanayaki, T. Ananthi. Hepatoprotective Activity of Aqueous Extract of Lawsonia inermis against Paracetamol Induced Rats. Asian J. Pharm. Res. 2012;  2(2): 75-77.
45.    T.S. Dhanaraj, R. Gowthami, S. Rajlakshmi, K. Murugaiah. Antihepatotoxicity of Hygrophila auriculata on CCl4 Induced Hepatotoxicity in Rats. Asian J. Res. Pharm. Sci. 2012; 2(4): 140-142.
46.    Pushpendra K. Patel, Narendra K. Prajapati, B.K. Dubey. Hepatotoxicity: Causes, Symptoms and Herbal Remedies. Research J. Pharmacognosy and Phytochemistry 2012; 4(2): 104-111.
47.    Venkatalakshmi P., Ragadevi M. Protective effect of Tinospora cordifolia linn., on Paracetamol and Alcohol Induced Hepatotoxicity in Albino Rats. Research J. Pharm. and Tech. 2012; 5(2): 281-284.
48.    V. Sreedhar, L.K. Ravindra Nath, N. Madana Gopal, K. Venu Gopal, D.Raju, K.K. Rajasekhar. Hepatoprotective Activity of Vitex quinata Roots against Paracetamol-Induced Hepatic Injury in Rats. Research J. Pharmacognosy and Phytochemistry 2011; 3(2): 77
49.    Kanakam Vijayabhaskar, Goli Venkateshwarlu, J. Bhaskar, K. Srisailam, More Swapna. Antioxidant and Hepatoprotective Effects of the Methanol Extract of the Flowers of Tamarindus indica. Asian J. Pharm. Tech. 2011; 1(3): 73-78.
50.    S.S. Oda, I.M. El-Ashmawy, Protective effect of silymarin on mercury-induced acute nephro- hepatotoxicity in rats, Global Vet. 2012; 9(4): 376–83.
51.    G. Jagdeesan, Mercury poisoning and its antidotes – A review, Biochem. Cell Arch. (2004); 4(2): 61–6.
52.    G. Jagadeesan, S. Sankarsamipillai, Hepatoprotective effects of taurine against mercury induced toxicity in rats, J. Environ. Biol. 2007; 28(4): 753–6.
53.    J.P. Cheng, W.X. Hu, X.J.M. Lin, W. Shi, W.H. Wang, Expression of C-fos and oxidative stress on brain of rats reared on food from mercury-selenium coexisting mining area, J. Environ. Sci. (China). 2006; 18(4): 788–92.
54.    S. Sankarsamipillai, G. Jagadeesan, S. Ramesh, P. Arumugam, Role of Taurine and Glutathione treatment on lipid peroxidation and antioxidant defense in mercury induced toxicity in rats, Int. J. Hum. Sci. Tech. 2010; 1(1): 72–81.
55.    S. Kalender, F.G. Uzun, F. Demir, M. Uzunhisarcıklı, A. Aslanturk, Mercuric chloride induced testicular toxicity in rats and the protective role of sodium selenite and vitamin E, Food Chem. Toxicol. 2013; 55: 456–462.
56.    Y. Deng, Z. Xu, W. Liu, H. Yang, B. Xu, Y. Wei, Effects of lycopene and proanthocyanidins on hepatotoxicity induced by mercuric chloride in rats, Biol. Trace Elem. Res. 2012; 146 (2): 213–223.
57.    Vadapalli Umarani, Muvvala Sudhakar, Alluri Ramesh. Protective Potential effect of Gloriosa superba Linn. against lead Nitrate Induced Oxidative stress in Rats. Asian J. Res. Pharm. Sci. 2019; 9(3):186-192. doi: 10.5958/2231-5659.2019.00029.8
58.    M. Kirici, C. Turk, C. Caglayan, M. Kirici, Toxic effects of copper sulphate pentahydrate on antioxidant enzyme activities and lipid peroxidation of freshwater fish Capoeta umbla (Heckel, 1843) tissues, Appl. Ecol. Environ. Res. 2017; 15: 1685–1696.
59.    Maharaja P, Sengottuvel T, Aarthi A, Gopalasatheeskumar K. Review on Antioxidant and Hepatoprotective activity of Medicinal plants against Paracetamol Induced animal model. Res. J. Pharmacognosy and Phytochem. 2020; 12(2): 114-119. doi: 10.5958/0975-4385.2020.00020.5
60.    E. Bharathi, G. Jagadeesan, Antioxidant potential of hesperidin and ellagic acid on renal toxicity induced by mercuric chloride in rats, Biomed. Prev. Nutr. 2014; 4 (2): 131–136.
61.    M.S. Othman, G. Safwat, M. Aboulkhair, A.E.A. Moneim, The potential effect of berberine in mercury-induced hepatorenal toxicity in albino rats, Food Chem. Toxicol. 2014; 69: 175–18149.
62.    J. Yi, W. Xia, J. Wu, L. Yuan, J. Wu, D. Tu, J. Fang, Z. Tan, Betulinic acid prevents alcohol-induced liver damage by improving the antioxidant system in mice, J. Vet. Sci. 2014; 15 (1): 141-148.
63.    R. Fan, P.c. Hu, Y. Wang, H.y. Lin, K. Su,X.s. Feng, L. Wei, F. Yang, Betulinic acid protects mice from cadmium chloride-induced toxicity by inhibiting cadmium-induced apoptosis in kidney and liver, Toxicol. Lett. 2018; 299: 56-66.
64.    S. Ansar, M. Iqbal, Protective effect of diallylsulphide against mercuric chloride-induced hepatic injury in rats, Hum. Exp. Toxicol. 2016; 35 (12): 1305–1311.
65.    P. Malini, G. Kanchana, M. Rajadurai, Antiperoxidative and antioxidant effect of ellagic acid on normal and streptozotocin induced diabetes in albino wistar rats, Res. J. Pharm. Biol. Chem. Sci. 2011; 2 (3): 24–34.
66.    Y. Necib, A. Bahi, S. Zerizer, Amelioration of mercuric chloride toxicity on rat liver with argan oil and sodium selenite supplements, Int. J. Pharm. Biomed. Sci. 2013; 4B (2): 839–49.
67.    Y. Necib, A. Bahi, S. Zerizer, Argan oil (Argania spinosa L) provides protection against mercuric chloride induced oxidative stress in rat Albinos Wistar, Int. J. Basic Appl. Sci. 2013; 2 (1): 73–80.
68.    Sathyaseelan Thennarasan, Subbiah Murugesan, Vajiravelu Sivamurugan. Hepatoprotective activity of Brown Alga Lobophora variegata against Chromium Induced Oxidative Damage in Wistar Rats. Res. J. Pharmacology and Pharmacodynamics.2017; 9(2): 61-69. doi: 10.5958/2321-5836.2017.00011.8
69.    T. Sugunavarman, G. Jagadeesan, S. Sankarsamipillai, Tribulus terrestris extract protects against mercury-oxidative tissue damage in mice, J. Ecobiotech. 2010; 2(1): 59–65.
70.    S. Sankarsamipillai, G. Jagadeesan, Protective role of Taurine against mercuric chloride intoxicated rats, Recent Res. Sci. Technol. 2009; 1 (2): 81–7.

Recomonded Articles:

Research Journal of Pharmacy and Technology (RJPT) is an international, peer-reviewed, multidisciplinary journal.... Read more >>>

RNI: CHHENG00387/33/1/2008-TC                     
DOI: 10.5958/0974-360X 

56th percentile
Powered by  Scopus

SCImago Journal & Country Rank

Recent Articles


Not Available