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Drug Res (Stuttg) 2015; 65(1): 30-39
DOI: 10.1055/s-0034-1371829
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Hepatoprotective and Antioxidant Activities of Hepacare®, a Herbal Formulation Against Carbon Tetrachloride-Induced Liver Injury

I. O. Ishola
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, ­University of Lagos, Lagos, Nigeria
,
A. A. Akinyede
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, ­University of Lagos, Lagos, Nigeria
,
A. K. Robert
1   Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, ­University of Lagos, Lagos, Nigeria
,
S. A. Omilabu
2   Virology Unit, Department of Microbiology and Parasitology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
› Author Affiliations
Further Information

Publication History

received 09 January 2014

accepted 25 February 2014

Publication Date:
07 April 2014 (online)

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Abstract

Background:

Hepacare® is a herbal formulation used to treat patients with sickle-cell anaemia complicated with jaundice, also recommended as a protective agent against liver damage due to chronic ingestion of alcohol.

Methods:

In vitro antioxidant properties of Hepacare® was determined using 1, 1- diphenyl-2-picryl-hydrazyl (DPPH), total antioxidant capacity, reducing power ability, and nitric oxide assays. Hepatoprotective effect of Hepacare® (50–400 mg/kg/day for 7 days, p.o.) was investigated in male Sprague Dawley rats against carbon tetrachloride (CCl4 /olive oil, 1:1, 0.7 ml/kg, i.p.)-induced liver damage. At the end of the study, blood samples and liver tissue were assayed for biochemical and antioxidants parameters.

Results:

Hepacare produced concentration dependent inhibition of DPPH and nitric oxide activity with IC50 of 48.50 and 55.00 µg/ml, respectively, it suppressed the absorbance of ABTS.+ with total antioxidant capacity of 423.47±8.37 mg QUE/g. CCl4 administration induced significant (P<0.001) elevation of serum aspartate transaminase (1.70 fold), alanine transaminase (1.60 fold), alkaline phosphatase (2.90 fold) and bilirubin (2.00 fold) in comparison to control. The increase in serum biomarker were dose-depen­dently reversed by Hepacare® pretreatment. More­over, CCl4 pretreatment increased (P<0.001) malondialdehyde (MDA) (73.98%) and decreased (P<0.001) antioxidant enzymes level but Hepacare pretreatment produced dose-dependent attenuation of the increased MDA (3.84 fold) with enhancement of glutathione (3.08 fold), superoxide dismutase (2.08 fold), and catalase (3.14 folds) levels in comparison to CCl4 treated group, similar to those of silymarin reference standard.

Conclusion:

Hepacare was beneficial in the prevention of CCl4-induced hepatocellular injury, possibly by scavenging reactive free radicals, and boosting endogenous antioxidant systems.

Key words

antioxidant systems - DPPH - flavonoid - hepatotoxicity - liver tonic - oxidative stress - reducing power capacity - serum transaminases
 

  • References

  • 1 Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Alimentary Pharmacol Ther 2011; 34: 274-285
    CrossrefPubMedGoogle Scholar
  • 2 Abbound G, Kaplowitz N. Drug induced liver injury. Drug Saf 2007; 30: 277-294
    CrossrefPubMedGoogle Scholar
  • 3 Kalyani GA, Ramesh CK, Krishna V. Hepatoprotective and antioxidant activities of Desmodium triquetrum DC. Indian J Pharm Sci 2011; 73: 463-466
    PubMedGoogle Scholar
  • 4 Medina J, Moreno-Otero R. Pathophysiological basis for antioxidant therapy in chronic liver disease. Drugs 2005; 65: 2445-2465
    CrossrefPubMedGoogle Scholar
  • 5 Williams AT, Burk RF. Carbon tetrachloride hepatotoxicity: an example of free radical mediated injury. Semin Liver Dis 1990; 10: 279-284
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Recknagel RO, Glende Jr EA, Dolak JA et al. Mechanism of carbon tetrachloride toxicity. Pharmacol Ther 1989; 43: 139-154
    CrossrefPubMedGoogle Scholar
  • 7 Verma S, Thuluvath PJ. Complementary and alternative medicine in hepatology: Review of the evidence of efficacy. Clin Gastroenterol Hepatol 2007; 5: 408-416
    CrossrefPubMedGoogle Scholar
  • 8 Braca A, De Tommasi N, Di Bari L et al. Antioxidant principles from Bauhinia terapotensis. J Nat Prod 2001; 64: 892-895
    CrossrefPubMedGoogle Scholar
  • 9 Viturro C, Molina A, Schmeda-Hirschmann G. Free radical scavengers from Mutisia friesiana (Asteraceae) and Sanicula graveolens (Apiaceae). Phytother Res 1999; 13: 422-424
    CrossrefPubMedGoogle Scholar
  • 10 Prieto P, Pineda M, Aguilar M. Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: Specific application to the determination of vitamin E. Anal Biochem 1999; 269: 337-341
    CrossrefPubMedGoogle Scholar
  • 11 Chia CC, Ming HY, Hwei MW et al. Estimation of total phenolic content by two complementary colorimetric methods. J Food Drug Anal 2002; 10: 163-173
    PubMedGoogle Scholar
  • 12 Karunakaran K. Estimation of total flavonoid content in propolis by two complementary colorimetric methods. J Food Drug Anal 2007; 10: 178-182
    PubMedGoogle Scholar
  • 13 Chanwitheesuk A, Teerawutgulrag A, Rakariyatham N. Screening of antioxidant activity and antioxidant compounds of some edible plants of Thailand. Food Chem 2005; 92: 491-497
    CrossrefPubMedGoogle Scholar
  • 14 Oyaizu M. Studies on product of browning reaction prepared from glucose amine. Japanese Journal of Nutrition 1986; 44: 307-315
    CrossrefPubMedGoogle Scholar
  • 15 Garratt DC. The quantitative analysis of Drugs. Volume 3. Chapman and Hall ltd; Japan: 1964: 456-458
    Google Scholar
  • 16 NIH. Guide for the Use of Laboratory Animals DHHS, PHS. NIH Publication No. 85-23 (1985 Revised)
    PubMedGoogle Scholar
  • 17 Habbu PV, Shastry RA, Mahadevan KM et al. Hepatoprotective and antioxidant effects of Argyreia speciosa in rats. African Journal of Traditional, Complementary and Alternative Medicine 2008; 5: 158-164
    PubMedGoogle Scholar
  • 18 Soon YY, Tan BKH. Evaluation of the hypoglycaemic and antioxidant activities of Morinda officinalis in streptozocin-induced diabetic rats. Singapore Med J 2002; 43: 077-085
    PubMedGoogle Scholar
  • 19 Galigher AE, Kozloff EN. Essentials of Practical Microtechniques. 2nd (ed.). Lea and Febiger; Philadelphia: 1971: 77
    Google Scholar
  • 20 Brand-Williams W, Cuvelier ME, Berset C. Use of a free radical method to evaluate antioxidant activity. LWT Food Sci Technol 1995; 28: 25-30
    CrossrefPubMedGoogle Scholar
  • 21 Conforti F, Marrelli M, Carmela MC et al. Bioactive phytonutrients (omega fatty acids, tocopherols, polyphenols), in vitro inhibition of nitric oxide production and free radical scavenging activity of non-cultivated Mediterranean vegetables. Food Chem 2011; 129: 1413-1419
    CrossrefPubMedGoogle Scholar
  • 22 Nijveldt RJ, van Nood E, van Hoorn DEC et al. Flavonoids: A review of probable mechanisms of action and potential applications. Am J Clin Nutr 2001; 74: 418
    PubMedGoogle Scholar
  • 23 Govind P. Medicinal plants against liver diseases. IJPR 2011; 2: 115-121
    PubMedGoogle Scholar
  • 24 Nunes PX, Silva SF, Guedes RJ et al. Biological oxidations and antioxidant activity of natural products, phytochemicals as nutraceuticals – Global Approaches to Their Role in Nutrition and Health. 2012
    PubMedGoogle Scholar
  • 25 Sharififar F, Dehghn-Nudeh G, Mirtajaldini M. Major flavonoids with antioxidant activity from Teucrium polium L. Food Chem 2009; 112: 885-888
    CrossrefPubMedGoogle Scholar
  • 26 Saeed N, Khan MR, Shabbir M. Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement Altern Med 2012; 12: 221
    CrossrefPubMedGoogle Scholar
  • 27 Shimoda H, Tanaka J, Kikuchi M et al. Walnut polyphenols prevent liver damage induced by carbon tetrachloride and d-galactosamine: hepatoprotective hydrolyzable tannins in the kernel pellicles of ­walnut. J Agric Food Chem 2008; 56: 4444-4449
    CrossrefPubMedGoogle Scholar
  • 28 Gordon MH In: Food antioxidants. Hudson BJ. (ed.). London: Elsevier Applied Science. The mechanism of antioxidant action in vitro; 1990: 18
    Google Scholar
  • 29 Kimura Y, Okuda H, Mori K et al. Studies on the activities of tannins and related compounds from medicinal plants and drugs, IV: Effects of various extracts of Geranii herba and Geraniin on liver injury and lipid metabolism in rats fed peroxidized oil. Chem Pharm Bull 1984; 32: 1866-1871
    CrossrefPubMedGoogle Scholar
  • 30 Mahadevappa P, Chapeyil KR, Venkatarangaiah K et al. Hepatoprotective and in vitro antioxidant effect of Carthamus tinctorious L, var Annigeri-2-, an oil-yielding crop, against CCl4-induced liver injury in rats. Pharmacogn Mag 2011; 7: 289-297
    CrossrefPubMedGoogle Scholar
  • 31 Khan RA, Khan MR, Sahreen S et al. Assessment of flavonoids contents and in vitro antioxidant activity of Launaea procumbens. Chem Cent J 2012; 6: 43
    CrossrefPubMedGoogle Scholar
  • 32 Gardner CR, Heck DE, Yang CS et al. Role of nitric oxide in acetaminophen-induced hepatotoxicity in the rat. Hepatol 1998; 27: 748-754
    CrossrefPubMedGoogle Scholar
  • 33 Recknagel RO, Glende Jr EA, Dolak JA et al. Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 1989; 43: 139-154
    CrossrefPubMedGoogle Scholar
  • 34 Manibusan MK, Odin M, Eastmond DA. Postulated carbon tetrachloride mode of action: a review. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2007; 25: 185-209
    CrossrefPubMedGoogle Scholar
  • 35 Lin X, Liu X, Huang Q et al. Hepatoprotective Effects of the Polysaccharide Isolated from Tarphochlamys affinis (Acanthaceae) against CCl4-Induced Hepatic Injury. Biol Pharm Bull 2012; 35: 1574-1580
    PubMedGoogle Scholar
  • 36 Williams AT, Burk RF. Carbon tetrachloride hepatotoxicity: an example of free radical-mediated injury. Semin Liver Dis 1990; 10: 279-284
    Article in Thieme ConnectPubMedGoogle Scholar
  • 37 De Groot H, Sies H. Cytochrome P-450, reductive metabolism, and cell injury. Drug Metab Rev 1989; 20: 275-284
    CrossrefPubMedGoogle Scholar
  • 38 Islam R, Parvin S, Islam E. Antioxidant and hepatoprotective activity of an ethanol extract of Syzygium jambos (L.) leaves. Drug Discoveries Ther 2012; 6: 205-211
    PubMedGoogle Scholar
  • 39 Zheng QS, Sun X, Xu B et al. Mechanisms of apigenin-7-glucoside as a hepatoprotective agent. Biomed Environ Sci 2005; 18: 65-70
    PubMedGoogle Scholar