Differential response of antioxidant defense in HepG2 cells on exposure of Livotrit®, in a concentration dependent manner

10.1016/j.jtcme.2017.08.007

S.A. Malik；S. Khole；S.P.K. Mittal；T. Urmode；R. Kusurkar；S.S. Ghaskadbi

Antioxidant enzymes ； HO-1 ； BACH-1 ； miRNA

Journal of Traditional and Complementary Medicine

9卷1期（2019 / 01 / 01）

38 - 44

英文

Livotrit®, a polyherbal formulation (Zandu, India) is commonly prescribed for liver health. The present study was undertaken to elucidate possible mechanism of antioxidant potential of Livotrit®. Livotrit® exhibited concentration dependent radical scavenging activity, inhibition of lipid peroxidation as well as activation and gene expression of antioxidant enzymes. Interestingly, lower concentration of Livotrit® (0.05%) significantly increased activities and gene expression of catalase, Glutathione reductase (GR) and Gluthathione peroxidase (GPx), while higher concentration of Livotrit® (0.5%) significantly increased antioxidant enzyme Heme-oxygenase 1(HO-1) and not catalase (CAT), GR and GPx. Transcription factor, Nuclear factor erythroid 2-related factor 2 (Nrf2) required for expression of catalase, GR, GPx and HO-1 was efficiently translocated into the nucleus at both concentrations. Inspite of this, concentration dependent activation of these enzymes was found to be mediated through miRNAs involved in regulation of their gene expression.

1. Aebi, H(1984).Catalase in vitro.Methods Enzym,105,121-126.
2. Aquino, R,Morelli, S,Lauro, MR,Abdo, SA,Saija, A,Tomaino, A(2001).Phenolic constituents and antioxidant activity of an extract of anthurium v ersicolor leaves.J Nat Prod,64,1019-1023.
3. Aruoma, O(1994).Nutrition and health aspects of free radicals and antioxidants.Food Chem Toxicol,32,671-683.
4. Bermeyer, HU(ed.)(1983).Methods of Enzymatic Analysis.Weinhein:Verlagchemie GmbH.
5. Bradford, MM(1976).A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.Anal Biochem,72,248-254.
6. Cheng, X,Ku, CH,Siow, RC(2013).Regulation of the Nrf2 antioxidant pathway by microRNAs: new players in micromanaging redox homeostasis.Free Radic Biol Med,64,4-11.
7. Devasagayam, TP,Pushpendran, CK,Eapen, J(1983).Differences in lipid peroxidation of rat liver rough and smooth microsomes.Biochim Biophys Acta,750,91-97.
8. Dixit, P,Ghaskadbi, S,Mohan, H,Devasagayam, TP(2005).Antioxidant properties of germinated fenugreek seeds.Phyto Res,19,977-983.
9. Dong, X,Liu, H,Chen, F,Li, D,Zhao, Y(2014).MiR-214 promotes the alcohol-induced oxidative stress via down-regulation of glutathione reductase and cytochrome P450 oxidoreductase in liver cells.Alcohol Clin Exp Res,38,68-77.
10. Girish, C,Koner, B,Jayanthi, S,Rao, K,Rajesh, B,Pradhan, S(2009).Hepatoprotective activity of six polyherbal formulations in paracetamol induced liver toxicity in mice.Indian J Med Res.,129,569-578.
11. Govindarajan, R,Vijayakumar, M,Rawat, A,Mehrotra, S(2003).Free radical scavenging potential of Picrorhiza kurrooa Royle ex Benth.Indian J Exp Biol,41,875-879.
12. Goyal, B,Bansal, P,Gupta, V,Kumar, S,Singh, R,Maithani, M(2010).Pharmacological potential of Boerhaavia diffusa: an overview.Int J Pharm Sci Drug Res,2,17-22.
13. Halliwell, B(1999).Antioxidant defence mechanisms: from the beginning to the end (of the beginning).Free Rad Res,31,261-272.
14. Haque, R,Chun, E,Howell, JC,Sengupta, T,Chen, D,Kim, H(2012).MicroRNA-30bmediated regulation of catalase expression in human ARPE-19 cells.PLoS One,7,e42542.
15. Jian, Z,Li, K,Liu, L(2011).Heme oxygenase-1 protects human melanocytes from H2O2-induced oxidative stress via the Nrf2-ARE pathway.J Invest Dermatol,131,1420-1427.
16. Jing, G,Xuechao, S,Guonian, W,Mingming, L,Meng, C(2011).Icariside II enhances Nrf2 nuclear translocation to upregulate phase II detoxifying enzyme expression coupled with the ERK, Akt and JNK signaling pathways.Molecules,16,9234-9244.
17. Lawrence, RA,Burk, RF(1976).Glutathione peroxidase activity in selenium-deficient rat liver.Biochem Biophys Res Commun,71,952-958.
18. Motterlini, R,Foresti, R,Bassi, R,Green, CJ(2000).Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress.Free Radic Biol Med,28,1303-1312.
19. Niranjan, A,Tewari, S,Lehri, A(2010).Biological activities of kalmegh (Andrographis paniculata Nees).Indian J Nat Prod Res,1,125-135.
20. Rice-Evans, C,Miller, NJ(1994).Total antioxidant status in plasma and body fluids.Methods Enzym,234,279-293.
21. Shan, Y,Lambrecht, RW,Ghaziani, T,Donohue, SE,Bonkovsky, HL(2004).Role of Bach-1 in regulation of heme Oxygenase-1 in human liver cells: insights from studies with small interfering RNAs.J Biol Chem,279,51769-51774.
22. Teixeira, HD,Meneghini, R(1996).Chinese hamster fibroblasts overexpressing CuZn-superoxide dismutase undergo a global reduction in antioxidants and an increasing sensitivity of DNA to oxidative damage.Biochem J,315,821-825.
23. Wang, L,Huang, H,Fan, Y(2014).Effects of downregulation of microRNA-181a on H2O2-induced H9c2 cell apoptosis via the mitochondrial apoptotic pathway.Oxid Med Cell Longev,1-16.
24. Wu, D,Cederbaum, AI(1996).Ethanol cytotoxicity to a transfected HepG2 cell line expressing human cytochrome P4502E1.J Biol Chem,271,23914-23919.
25. Young, I,Woodside, J(2001).Antioxidants in health and disease.J Clin Pathol,54,176-186.