Toxicological evaluation of Terminalia paniculata bark extract and its protective effect against CCl4-induced liver injury in rodents

BMC Complementary and Alternative Medicine

Krishnadas Nandakumar¹  Rekha R Shenoy¹  Punit Bansal¹  Anoop Kishore¹  Nitesh Kumar¹  Pawan G Nayak¹  Hitesh V Jagani²  Sahil Talwar¹ 

[1] Department of Pharmacology, Manipal College of Pharmaceutical Sciences,Manipal University, Manipal, Karnataka 576 104, India;Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Manipal University, Manipal, Karnataka 576 104, India

关键词: Apoptotic markers;    Mitochondrial staining;    CCl₄-induced liver toxicity;    Hepatoprotective;    Antioxidant;    Terminalia paniculata;   

Others  :  1229858
DOI  :  10.1186/1472-6882-13-127

 received in 2013-01-16, accepted in 2013-05-28,  发布年份 2013

【 摘 要 】

Background

Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage.

Methods

Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl₄-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl₄ administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl₄-treated Chang cells were also elucidated.

Results

TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl₄. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl₄-treated Chang cells, improving the viability considerably.

Conclusion

The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress.

【 授权许可】

   
2013 Talwar et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Somasundaram A, Karthikeyan R, Velmurugan V, Dhandapani B, Raja M: Evaluation of hepatoprotective activity of Kyllinga nemoralis (Hutch & Dalz) rhizomes. J Ethnopharmacol 2010, 127:555-557.
• [2]Fadhel ZA, Amran S: Effects of black tea extract on carbon tetrachloride-induced lipid peroxidation in liver, kidneys, and testes of rats. Phytother Res 2002, 16:S28-S32.
• [3]Nadkarni AK: Terminalia paniculata Roxb. In Dr KM Nadkarni’s Indian Materia Medica. Volume 1. 3rd edition. Mumbai, India: Popular Prakashan; 1996:931.
• [4]Talwar S, Nandakumar K, Nayak PG, Bansal P, Mudgal J, Mor V, Rao CM, Lobo R: Anti-inflammatory activity of Terminalia paniculata bark extract against acute and chronic inflammation in rats. J Ethnopharmacol 2011, 134:323-328.
• [5]Singh K, Khanna AK, Chander R: Hepatoprotective activity of ellagic acid against carbon tetrachloride induced hepatotoxicity in rats. Indian J Exp Biol 1999, 37:1025-1026.
• [6]Yuan HD, Jin GZ, Piao GC: Hepatoprotective effects of an active part from Artemisia sacrorum Ledeb. against acetaminophen-induced toxicity in mice. J Ethnopharmacol 2010, 127:528-533.
• [7]Dhanasekaran M, Ignacimuthu S, Agastian P: Potential hepatoprotective activity of ononitol monohydrate isolated from Cassia tora L. on carbon tetrachloride induced hepatotoxicity in wistar rats. Phytomedicine 2009, 16:891-895.
• [8]Huang B, Ban X, He J, Zeng H, Zhang P, Wang Y: Hepatoprotective and antioxidant effects of the methanolic extract from Halenia elliptica. J Ethnopharmacol 2010, 131:276-281.
• [9]Yan XB, Mei L, Feng X, Wan MR, Chen Z, Pavio N, Brechot C: Hepatitis C virus core proteins derived from different quasi species of genotype 1b inhibit the growth of Chang liver cells. World J Gastroenterol 2008, 14:2877-2881.
• [10]Houghton P, Fang R, Techatanawat I, Steventon G, Hylands PJ, Lee CC: The sulphorhodamine (SRB) assay and other approaches to testing plant extracts and derived compounds for activities related to reputed anticancer activity. Methods 2007, 42:377-387.
• [11]McManus JFA, Mowry RW: Staining methods: histologic and histochemical. New York, NY: Harper and Row; 1965.
• [12]Malloy HT, Evelyn KA: The determination of bilirubin with the photoelectric colorimeter. J Biol Chem 1937, 119:481-490.
• [13]Raj PV, Nitesh K, Gang SS, Jagani HV, Chandrashekhar HR, Rao JV, Rao CM, Udupa N: Protective role of catechin on d-galactosamine induced hepatotoxicity through a p53 dependent pathway. Indian J Clin Biochem 2010, 25:349-356.
• [14]Krithika R, Mohankumar R, Verma RJ, Shrivastav PS, Mohamad IL, Gunasekaran P, Narasimhan S: Isolation, characterization and antioxidative effect of phyllanthin against CCl4-induced toxicity in HepG2 cell line. Chem Biol Interact 2009, 181:351-358.
• [15]Jain A, Soni M, Deb L, Rout SP, Gupta VB, Krishna KL: Antioxidant and hepatoprotective activity of ethanolic and aqueous extracts of Momordica dioica Roxb. leaves. J Ethnopharmacol 2008, 115:61-66.
• [16]Chang RS: Continuous subcultivation of epithelial-like cells from normal human tissues. Proc Soc Exp Biol Med 1954, 87:440-443.
• [17]Manna P, Sinha M, Sil PC: Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders. BMC Complement Altern Med 2006, 6:33. BioMed Central Full Text
• [18]Raja S, Ahamed KF, Kumar V, Mukherjee K, Bandyopadhyay A, Mukherjee PK: Antioxidant effect of Cytisus scoparius against carbon tetrachloride treated liver injury in rats. J Ethnopharmacol 2007, 109:41-47.
• [19]Seifried HE, Anderson DE, Fisher EI, Milner JA: A review of the interaction among dietary antioxidants and reactive oxygen species. J Nutr Biochem 2007, 18:567-579.
• [20]Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J: Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007, 39:44-84.
• [21]Tabatabaie T, Floyd RA: Susceptibility of glutathione peroxidase and glutathione reductase to oxidative damage and the protective effect of spin trapping agents. Arch Biochem Biophys 1994, 314:112-119.
• [22]Duchen MR: Roles of mitochondria in health and disease. Diabetes 2004, 53:S96-S102.
• [23]Thompson T, Tovar C, Yang H, Carvajal D, Vu BT, Xu Q, Wahl GM, Heimbrook DC, Vassilev LT: Phosphorylation of p53 on key serines is dispensable for transcriptional activation and apoptosis. J Biol Chem 2004, 279:53015-53022.
• [24]Cory S, Adams JM: The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer 2002, 2:647-656.
• [25]Kroemer G, Galluzzi L, Brenner C: Mitochondrial membrane permeabilization in cell death. Physiol Rev 2007, 87:99-163.
• [26]Boulares AH, Yakovlev AG, Ivanova V, Stoica BA, Wang G, Iyer S, Smulson M: Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem 1999, 274:22932-22940.
• [27]Jadon A, Bhadauria M, Shukla S: Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharmacol 2007, 109:214-218.
• [28]Vattem DA, Shetty K: Biological functionality of ellagic acid: a review. J Food Biochem 2005, 29:234-266.
• [29]Chattopadhyay RR: Possible mechanism of hepatoprotective activity of Azadirachta indica leaf extract: part II. J Ethnopharmacol 2003, 89:217-219.