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BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2017

Open Access 01-12-2017 | Research article

Hepatoprotective effect of the solvent extracts of Viola canescens Wall. ex. Roxb. against CCl4 induced toxicity through antioxidant and membrane stabilizing activity

Authors: Abdullah, Mir Azam Khan, Waqar Ahmad, Manzoor Ahmad, Mohammad Nisar

Published in: BMC Complementary Medicine and Therapies | Issue 1/2017

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Abstract

Background

Viola canescens Wall. ex. Roxb. exhibits analgesic, antimalarial and antispasmodic activities. It is used folklorically for the treatment of liver diseases, hypertension, malaria and cancer. The current study investigates phytochemical constituents, antioxidant and hepatoprotective activity of solvent extracts of whole plant of Viola canescens.

Methods

Phytochemicals, acute toxicity study and antioxidant activity of Viola canescens methanolic extract (VCME), ethyl acetate fraction (EAF), and partially purified EAF (90% EAF and combination of 80% EAF + 20% methanol fraction (EAF + Me) was carried out. Hepatoprotective activity of VCME, EAF (200 and 400 mg/kg body weight) and partially purified EAF (50 mg/kg body weight) was investigated in carbon tetrachloride (CCl4) intoxicated BALB/c mice for 7 days. Membrane stabilization effect was determined by hypotonic solution induced hemolysis while DNA ladder assay was carried out by polyacrylamide gel electrophoresis.

Results

Phytochemical screening of VCME showed the presence of alkaloids, phenols, flavonoids, saponins, carbohydrates, tannins and triterpenes. VCME, EAF (at 200 and 400 mg/kg body weight) and partially purified EAF (90% EAF and EAF + Me) at 50 mg/kg body weight significantly reduced the level of ALT, ALP, total bilirubin and restored the level of serum protein in comparison to CCl4 treated group. A significant reduction in malondialdehyde (MDA) and elevation in catalase (CAT) and superoxide dismutase (SOD) level was observed in extract treated animals as compared to CCl4 (p < 0.05). The IC50 values in membrane stabilization potential for VCME, EAF and sodium salicylate were 3.7 ± 0.11, 3.4 ± 0.15 and 3.2 ± 0.09 mg/ml, respectively. Similarly, CCl4 induced degradation of DNA was counteracted by VCME and EAF. The liver biopsy of mice treated with the solvent extracts showed remarkable restoration of normal histological archeitecture.

Conclusions

Viola canescens showed significant hepatoprotective potential due to its antioxidant and membrane stabilization effect.
Literature
1.
Lin HM, Tseng HC, Wang CJ, Lo CW, Chou FP. Hepatoprotective effects of Solanum nigrum Linn extract against CCl4-iduced oxidative damage in rats. Chem Biol Interact. 2008;171:283–93.CrossRefPubMed
2.
Khan RA, Khan MR, Ahmed M, Sahreen S, Shah NA, Shah MS, Bokhari J, Rashid U, Ahmad B, Jan S. Hepatoprotection with a chloroform extract of Launaea procumbens against CCl4-induced injuries in rats. BMC Complement Altern Med. 2012;12:114.CrossRefPubMedPubMedCentral
3.
Stoyanovsky DA, Cederbaum AI. Thiol oxidation and cytochrome P450-dependent metabolism of CCl4 triggers Ca2+ release from liver microsomes. Biochemistry. 1996;35:15839–45.CrossRefPubMed
4.
Frank H, Link B. Anaerobic metabolism of carbon tetrachloride and formation of catabolically resistant phospholipids. Biochem Pharmacol. 1984;33:1127–30.CrossRefPubMed
5.
Recknagel RO, Ghoshal AK. Quantitative estimation of peroxidative degeneration of rat liver microsomal and mitochondrial lipids after carbon tetrachloride poisoning. Exp Mol Pathol. 1966;5:413–26.CrossRefPubMed
6.
Rector RS, Thyfault JP, Uptergrove GM, Morris EM, Naples SP, Borengasser SJ, Mikus CR, Laye MJ, Laughlin MH, Booth FW, Ibdah JA. Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model. J Hepatol. 2010;52:727–36.CrossRefPubMedPubMedCentral
7.
Kaplowitz N, Tsukamoto H. Oxidative stress and liver disease. Progr Liver Dis. 1996;14:131–59.PubMed
8.
9.
Zhang A, Sun H, Wang X. Recent advances in natural products from plants for treatment of liver diseases. Eur J Med Chem. 2013;63:570–7.CrossRefPubMed
10.
Edwards CRW, Bouchier IAD, Haslett C. Davidson’s principles and practice of medicine. 17th ed. Great Britain: BPC Paulton books limited; 1996.
11.
Au JS, Navarro VJ, Rossi S. Review article, Drug-induced liver injury—its pathophysiology and evolving diagnostic tools. Aliment Pharmacol The. 2011;34:11–20.CrossRef
12.
Madrigal-Santillan E, Madrigal-Bujaidar E, Alvarez-Gonzalez I, et al. Review of natural products with hepatoprotective effects. World J Gastroenterol. 2014;20:14787–804.CrossRefPubMedPubMedCentral
13.
Baranisrinivasan P, Elumalai EK, Sivakumar C, ViviyanTherasa S, David E. Hepatoprotective effect of Enicostemma littoraleblume and Eclipta alba during ethanol induced oxidative stress in albino rats. Int J Pharmacol. 2009;5:268–72.CrossRef
14.
Kren V, Walterova D. Silybin and silymarin–new effects and applications. Biomed Papers. 2005;149:29–41.CrossRef
15.
Woo JS, Kim TS, Park JH, Chi SC. Formulation and biopharmaceutical evaluation of silymarin using SMEDDS. Arch Pharm Res. 2007;30:82–9.CrossRefPubMed
16.
Wu JW, Lin LC, Tsai TH. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol. 2009;121:185–93.CrossRefPubMed
17.
18.
Soobrattee MA, Neergheen VS, Luximon-Ramma A, Aruoma OI, Bahorun T. Phenolics as potential antioxidant therapeutic agents: mechanism and actions. Mutat Res. 2005;579:200–13.CrossRefPubMed
19.
Qaiser M, Omer S. Violaceae. In: Nasir E, Ali SI, editors. Flora of Pakistan. 1985. p. 1–28.
20.
Zhua H, Qina SS, Zhang N, Yang DW, Han HR, Wei KH, Li MH. Chemical constituents and biological activities of plants from the Genus Viola. Chem Biod. 2015;12:1777–808.CrossRef
21.
Qadir MI, Ali M, Saleem M, Hanif M. Hepatoprotective activity of aqueous methanolic extract of Viola odorata against paracetamol-induced liver injury in mice. Bangladesh J Pharmacol. 2014;9:198–202.
22.
Bigoniya P, Singh CS. Hepatoprotective activity of luteolin from A. millefolium in CCl4 intoxicated rat model. Int J Ind Med Pla. 2013;46:2051–4263.
23.
Igarashi K, Mikami T, Takahashi Y, Sato H. Comparison of the preventive activity of isorhamnetin glycosides from Atsumi-kabu (Red Turnip, Brassica campestris L.) leaves on carbon tetrachloride-induced liver injury in mice. Biosci Biotechnol Biochem. 2008;72:856–60.CrossRefPubMed
24.
Vijayan P, Prashanth HC, Vijayaraj P, Dhanaraj SA, Badami S, Suresh B. Hepatoprotective effect of the total alkaloid fraction of Solanum pseudocapsicum leaves. Pharm Biol. 2003;41:443–8.CrossRef
25.
Lin J, Zhao J, Li T, Zhou J, Hu J, Hong Z. Hepatoprotection in a rat model of acute liver damage through inhibition of CY2E1 activity by total alkaloids extracted from Rubus alceifolius Poir. Int J Toxicol. 2011;30:237–43.CrossRefPubMed
26.
Rathi A, Srivastava AK, Shirwaikar A, Singh Rawat AK, Mehrotra S. Hepatoprotective potential of Fumaria indica Pugsley whole plant extracts, fractions and an isolated alkaloid protopine. Phytomedicine. 2008;15:470.CrossRefPubMed
27.
Verma G, Dua VK, Agarwal DD, Atul PK. Anti-malarial activity of Holarrhena antidysenterica and Viola canescens, plants traditionally used against malaria in the Garhwal region of north-west Himalaya. Malar J. 2011;10:20.CrossRefPubMedPubMedCentral
28.
Barkatullah, Ibrar M, Ali N, Muhammad N, Ehsan M. In-vitro pharmacological study and preliminary phytochemical profile of Viola canescens Wall. Ex Roxb. Afr J Pharm Pharmacol. 2012;6:1142–6.CrossRef
29.
Jan G, Khan MA, Gul F. Ethnomedicinal plants used against jaundice in Dir Kohistan Valleys (NWFP) Pakistan. Ethnobot Leafl. 2009;13:1029–41.
30.
Aneel GS, Qureshi RA, Gilani SJ. Indigenous uses of some important ethnomedicinal herbs of Ayubia National Park, Abbottabad Pakistan. Ethnobot Leafl. 2006;10:285–93.
31.
Ahmad L, Semotiuk A, Zafar M, Ahmad M, Sultana S, Liu QR, Zada MP, Abidin SZ, Yaseen G. Ethnopharmacological documentation of medicinal plants used for hypertension among the local communities of Dir Lower, Pakistan. J Ethnopharmacol. 2015;175:138–46.CrossRefPubMed
32.
Hamayun M, Khan SA, Sohn EY, Lee I. Folk medicinal knowledge and conservation status of some economically valued medicinal plants of District Swat, Pakistan. Lyonia. 2006;11:101–13.
33.
Williamson EM, Okpako DT, Evans FJ. Selection, Preparation and pharmacological evaluation of plant material. Chichester: Wiley; 1998.
34.
Tamokou JD, Mpetga DJS, Lunga PK, Tene M, Tane P, Kuiate JR. Antioxidant and antimicrobial activities of ethyl acetate extract, fractions and compounds from stem bark of Albizia adianthifolia (Mimosoideae). BMC Complement Altern Med. 2012;12:99.CrossRefPubMedCentral
35.
Mujwah AA, Mohammed MA, Ahmed MH. First isolation of a flavonoid from Juniperus procera using ethyl acetate extract. Arabian J Chem. 2010;3:85–8.CrossRef
36.
Harborne JB. Phytochemical Methods: A guide to modern techniques of plant analysis. 3rd ed. London: Chapman and Hall; 1998.
37.
Singleton VL, Rossi J.A. Colorimetry of total phenolic substances. US: American Chemical Society Symposium series. 1965; 26: 47–70.
38.
Park YS, Jung ST, Kang SG, Heo BK, Arancibia-Avila P, Toledo F, Zewiecki J, Namiesnik J, Gorinstein S. Antioxidants and proteins in ethylene-treated kiwifruits. Food Chem. 2008;107:640–8.CrossRef
39.
Braca A, Sortino C, Politi M, et al. Anti-oxidant activity of flavonoids from Licania licaniaeflora. J Ethnopharmacol. 2002;79:379–81.CrossRefPubMed
40.
Ruch RJ, Cheng SJ, Klaunig JE. Prevention of cytotoxicity and inhibition of intracellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogenesis. 1989;10:1003–8.CrossRefPubMed
41.
OECD. Guidelines for the testing of chemicals revised draft guideline 423: acute oral toxicity: Paris: OECD. 2000.
42.
Navaro MC, Montila MP, Martin A, Jimenez J, Utrilla M. Free radical scavenger and antihepatotoxic activity of Rosmarinus tomentosus. Planta Med. 1993;59:312–4.CrossRef
43.
Anand KK, Gupta VN, Rangari VD, Chandan BK. Structure and hepatoprotective activity of a biflavonoid from Canarium manii. Planta Med. 1992;58:493–5.CrossRefPubMed
44.
Beers RF, Seizer IW. A Spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem. 1952;195:133.PubMed
45.
Sagu H, Ohishi N, Dexr D. A selective increase in particular SOD activity in parkinsonism. J Neurochem. 1989;53:692–7.CrossRef
46.
Sevanian A, Ursini F. LPO in membranes and low density lipoproteins- Similarities and differences. J Biol Med. 2000;29:306–11.
47.
Sadique J, Al-Rqobahs WA, Bughaith, EI-Gindi AR. The bioactivity of certain medicinal plants on the stabilization of RBC membrane system. Fitoterapia. 1989;60:525–32.
48.
Kuo JH, Jan MS, Jeng J, Chiu HW. Induction of apoptosis in macrophages by air oxidation of dioleoylphosphatidylglycerol. J Control Release. 2005;108:442–52.CrossRefPubMed
49.
Johnston DE, Kroening C. Mechanism of early carbon tetra chloride toxicity in cultured rat hepatocytes. Pharmacol Toxicol. 1998;83:231–9.CrossRefPubMed
50.
Michael JD. The toxicologist’s pocket handbook. 2nd ed. New York: Informa Healthcare USA, Inc; 2008.
51.
Deng JS, Chang YC, Wen CL, Liao JC, Hou WC, Amagaya S, Huang SS, Huang GJ. Hepatoprotective effect of the ethanol extract of Vitis thunbergii on carbon tetrachloride-induced acute hepatotoxicity in rats through anti-oxidative activities. J Ethnopharmacol. 2012;142:795–803.CrossRefPubMed
52.
Singal AK, Jampana SC, Weinman SA. Antioxidants as therapeutic agents for liver disease. Liver Int. 2011;31:1432–48.
53.
Huang B, Ban XQ, He JS, Zeng H, Zhang P, Wang YW. Hepatoprotective and antioxidant effects of the methanolic extract from Halenia elliptica. J Ethnopharmacol. 2010;131:276–81.CrossRefPubMed
54.
Sundararajan R, Haja NA, Venkatesan K, Mukherjee K, Saha BP, Bandyopadhyay A, Mukherjee PK. Cystisus scoparius—A natural antioxidant. BMC Complement Altern Med. 2006;16:6–8.
55.
Awika JM, Rooney LW, Wu XL, Prior RL, Cisneros-Zevallos L. Screening methods to measure antioxidant activity of Sorghum (Sorghum bicolor) and Sorghum product. J Agr Food Chem. 2003;51:6657–62.CrossRef
56.
Halliwell B. Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med. 1991;91:14S–22.CrossRefPubMed
57.
Weber LW, Boll M, Stampfl A. Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model. Crit Rev Toxicol. 2003;33:105–36.CrossRefPubMed
58.
Drotman RB, Lawhorn GT. Serum enzymes are indicators of chemical induced liver damage. Drug Chem Toxicol. 1978;1:163–71.CrossRefPubMed
59.
Khan MR, Rizvi W, Khan GN, Khan RA, Shaheen S. Carbon tetrachloride induced nephrotoxicity in rat: Protective role of Digera muricata. J Ethnopharmacol. 2009;122:91–9.CrossRefPubMed
60.
Khan RA, Daud A. Protective effects of Digera muricata (L.) Mart. on testis against oxidative stress of carbon tetrachloride in rat. Toxicol. 2009;47:1393–9.
61.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxidation in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95:351–8.CrossRefPubMed
62.
Jia X, Han C, Chen J. Effect of tea on preneoplastic lesions and cell cycle regulators in rat liver. Cancer Epidemiol Biomarkers Prev. 2002;11:1663–7.PubMed
63.
Murugesan GS, Sathishkumar M, Jayabalan R, Binupriya AR, Swaminathan K, Yun SEZ. Hepatoprotective and curative properties of Kombucha tea against carbon tetrachloride induced toxicity. J Microbiol Biotechnol. 2009;19:397–402.CrossRefPubMed
64.
Peters JM, Boyd EM. Organ weights and water levels of the rat following reduced food intake. J Nutr. 1966;90:354–60.PubMed
65.
Pfeiffer CJ. A mathematical evaluation of the thymic weight parameter. Toxicol Appl Pharmacol. 1968;13:220–7.CrossRefPubMed
Metadata
Title
Hepatoprotective effect of the solvent extracts of Viola canescens Wall. ex. Roxb. against CCl4 induced toxicity through antioxidant and membrane stabilizing activity
Authors
Abdullah
Mir Azam Khan
Waqar Ahmad
Manzoor Ahmad
Mohammad Nisar
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2017
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-016-1537-7

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