Effects of Extract of Morus alba Linn. Callus and Mulberroside A on Glutathione Profiles in Paracetamol-Induced Oxidative Stress Mouse Livers

Main Article Content

Yonlada Sriset
Waraporn Putalun
Waranya Chatuphonprasert

Abstract

Introduction: Morus alba Linn. (Mulberry) has been used in Thai traditional medicine as a perspiration drug, and as a hepatoprotective and nephroprotective agent. Mulberroside A is the major bioactive compound of M. alba, possessing antioxidant and hepatoprotective activities. The objective of this study was to evaluate the effect of methanolic extract of M. alba callus (MA) and mulberroside A (MBS) on hepatic histopathology and the glutathione profile of livers of mice with paracetamol-induced oxidative stress. Methods: Seven-week-old male ICR mice were given paracetamol (400 mg/kg/day, p.o.), in combination with N-acetylcysteine (NAC) (300 mg/kg/day, i.p.), or MBS (50 mg/kg/day, i.p.), or MA (250, 500 and 1,000 mg/kg/day, i.p.) for 7 consecutive days, while the control group received the vehicle, 0.5% carboxymethylcellulose. Histopathological examination of the liver tissue was by hematoxylin and eosin staining and the reduced glutathione (GSH) and oxidized glutathione (GSSG) contents, and glutathione peroxidase (GPx) activities were determined. Results: Injury of hepatic tissue after receiving paracetamol was observed as pyknosis, the characteristic histopathology of necrosis and apoptosis. In addition, the levels of GSH and GSSG, and the activity of GPx were significantly decreased in mice receiving paracetamol. Treatment of paracetamol-induced oxidative stress mice with NAC, MBS, and MA reduced the hepatic tissue injury compared to the controls, in accordance with increased GSH and GSSG levels. Treatment with MBS and MA also significantly increased GPx activity. Conclusion: Paracetamol treatment diminished the glutathione profile and GPx activity in mouse livers leading to oxidative stress and hepatic injury. MBS and MA exhibited effective hepatoprotective activity by improving the glutathione profile and GPx activity. Therefore, MBS and MA may be worth further development as alternative medicines or health supplement products for hepatoprotection.

Article Details

Section
Pharmaceutical Sciences

References

Aftab N, Likhitwitayawuid K, Vieira A. Comparative antioxidant activities and synergism of resveratrol and oxyresveratrol. Nat Prod Res 2010; 24: 1726-33.

Caciatore I, Cornacchia C, Pinnen F, Mllica A, Stefano AD. Prodrug approach for increasing cellular glutathione levels. Molecules 2010; 15: 1242-64.

Chatuphonprasert W, Udomsuk L, Monthak O, Churikhit Y, Putalun W, Jarukamjorn K. Effect of Pueraria mirifica and miroestrol on the antioxidation-related enzyme in ovariectomized mice. J Pharm Pharmacol 2012; 65: 447-56.

D’Agata LD, Balistreri WF. Evaluation of liver disease in the pediatric patient. Pediatr Rev 1999; 20(11): 376-89.

Erfan N, Mirjam V, Dirk W, et al. Increased efflux of oxidized glutathione (GSSG) causes glutathione depletion and potentially diminishes antioxidant defense in sickle erythrocytes. Biochim Biophys Acta 2011; 1812(11): 1412-17.

Francesco M, Hariom Y, Upendra G, Amr H, Shalini J, Emilio M. Protective effect of a phytocompound on oxidative stress and DNA fragmentation against paracetamol induced-liver damage. Ann Hepatol 2009; 8(1): 50-6.

Galindo I, Hernaez B, Berna J, et al. Comparative inhibitory activity of the stilbene resveratrol and oxyresveratrol on African swine fever virus replication. Antiviral Res 2011; 9: 57-63.

Hamza RZ, Al-Harbi MS. Amelioration of paracetamol hepatotoxicity and oxidative stress on mice liver with silymarin and Nigella sativa extract supplement. Asian Pac J Trop Biomed 2015; 5(7): 521-31.

Hinson JA, Reid AB, Mccullough SS, James LP. Acetaminophen-induced hepatotoxicity: role of metabolic activation reactive oxygen/nitrogen species and mitochondrial permeability transition. Drug Metab Rev 2004; 36: 805-22.

Hodgman JM, Garrard RA. A review of acetaminophen poisoning. Crit Care Nurs Clin North Am 2012; 28: 499-516.

James LP, Mayeux PR, Hinson JA. Acetaminophen-induced hepatotoxicity. Drug Metab Dispos 2003; 31(12): 1499-506.

Jearapong N, Chatuphonprasert W, Jarukamjorn K. Effect of tetrahydrocurcumin on the profiles of drug-metabolizing enzymes induced by a high fat and high fructose diet in mice. Chem Biol Interact 2015; 239: 67-75.

Jin Zhou, Shun-xiang Li, Wei Wang, et al. Variation in the levels of mulberroside A, oxyresveratrol and resveratrol in mulberries in different seasons and during growth. Sci World J 2013; 2013: 1-7.

Kals J, Starkopf J, Zilmer M, et al. Antioxidant UPF1 attenuates myocardial stunning in isolated rat hearts. Int J Cardiol 2008; 125: 133-5.

Kidd PM. Glutathione: systemic protectant against oxidative and free radical damage. Altern Med Rev 1997; 1: 155-76.

Komaikul J, Kitisripanya T, Tanaka H, Sritularak B, Putalun W. Development of an enzyme-linked immunosorbent assay for specific detection of mulberroside A in mulberry (Morus alba L.) using anti-mulberroside A polyclonal antibody. Food Anal Method 2014; 7(1): 58-63.

Kondo S, Chatuphonprasert W, Jaruchotikamol A, Sakuma T, Nemoto N. Cellular glutathione content modulates the effect of andrographolide on β-naphthoflavone-induced CYP1A1 mRNA expression in mouse hepatocytes. Toxicology 2011; 280(1-2): 18-23.

Lipipun V, Sasivimolphan P, Yoshida Y, et al. Topical cream- based oxyresveratrol in the treatment of cutaneous HSV-1 infection in mice. Antiviral Res 2011; 91: 154-60.

Meyers LL, Beierschmitt WP, Khairallah EA, Cohen SD. Acetaminophen-induced inhibition of mitochondrial respiration in mice. Toxicol Appl Pharmacol 1998; 93: 378-87.

Polson J, Lee WM. The management of acute liver failure. Hepatology 2005; 41(5): 1179-97.

Qiu F, Komatsu K, Kawasaki K, Satio K, Yao XS, Kano Y. A novel stilbene glucoside, oxyresveratrol 3’-O-beta-glucopyranoside from the root bark of Morus alba. Planta Med 1996; 62(6): 559-61.

Rice-Evans CA, Miller NJ, Paganga G. Antioxidant properties of phenolic compounds. Trends Plant Sci 1997; 2(4): 152-9.

Saensouk P, Suddee N. Effect of NAA and BA on callus and shoot formation of Asparagus racemosus Wild. KKU Res J 2004; 9(2): 31-9.

Shah VN, Deval K. Hepatoprotective activity of leaves of Parkinsonia aculeate Linn. against paracetamol induced hepatotoxicity in rats. Int J Pharm 2011; 1(2): 59-66.

Shapoval GS, Gromovaia VF. Mechanism of antioxidant protection of an organism from oxidative stress. Ukr Biochem J 2003; 75(2): 5-13.

Shi L, Zhang Z, Jin J. Protective function of cis-mulberroside A and oxyresveratrol from Ramulus mori against ethanol-induced hepatic damage. Environ Toxicol Phar 2008; 26: 325-30.

Somparn N, Jitvaropas R, Saenthaweesuk S, Thuppia A. Hepatoprotective and antioxidant effects of Polygonum odoratum L. extract against acetaminophen-induced hepatotoxicity in rats. Thammasat Med J 2013; 13(4): 456-64.

Tengamnuay P, Pengrungruangwong K, Pheansri I, Likhitwitayawuid K. Artocarpus lakoocha heartwood extract as a novel cosmetic ingredient: evaluation of the in vitro anti-tyrosinase and in vivo skin whitening activities. Int J Cosmet Sci 2006; 28: 269-76.

Tiwari B, Khosa R. Hepatoprotective and antioxidant effect of Sphaeranthus indicus against acetaminophen–induced hepatotoxicity in rats. J Trop Med 2009; 6(2): 1-5.

Vale JA, Proudfoot AT. Paracetamol (acetaminophen) poisoning. Lancet Neurol 1995; 346(8974): 547-52.

Wuttidhammaved W. The Rattanakosin pharmacy ancient book. Bangkok: Odian store; 2007.

Yoshimatsu K. Tissue culture of medicinal plant: Micropropagation, transformation and production of useful secondary of metabolites. Stud Nat Prod Chem 2008; 34: 647-752.