Abstract
Alcoholic liver disease (ALD) is a common and serious threat to human health worldwide. In this study, the hepatoprotective effect of gastrodin against alcohol-induced liver injury in mice was examined. Mice with alcohol-induced hepatotoxicity were treated intragastrically with gastrodin (50, 80, or 100 mg/kg). The mice treated with gastrodin experienced better outcomes than those who received only one dose of alcohol (50%, 10 mL/kg b.w.). Gastrodin treatment reduced the activities of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), decreased hepatic malondialdehyde (MDA) content, and increased hepatic superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) activities in a dose-dependent manner. Gastrodin also alleviated histopathological changes induced by alcohol. Gastrodin protected against alcohol-induced increases in expression levels of the cytochrome P450 2E1 (CYP2E1) and mRNA levels of chemokine (C-X-C motif) ligand 1 (CXCL-1), interferon-γ (IFN-γ), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), vascular cell adhesion molecule 1 (VCAM-1), nuclear factor-kappa B (NF-κB), Toll-like receptor 4 (TLR-4), and activator of transcription 3 (STAT-3). Moreover, gastrodin-increased nuclear transcription factor 2 (Nrf2) translocates to the nucleus and enhanced the activity of anti-oxidant enzymes, and could thereby ameliorate alcohol-induced liver injury in mice. This study demonstrated that gastrodin may be an effective therapeutic agent against alcohol-induced liver injury.
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References
Bryan HK, Olayanju A, Goldring CE, Park BK (2013) The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochem Pharmacol 85:705–717. https://doi.org/10.1016/j.bcp.2012.11.016
Cederbaum AI, Lu Y, Wu D (2009) Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol 83:519–548. https://doi.org/10.1007/s00204-009-0432-0
Ceni E, Mello T, Galli A (2014) Pathogenesis of alcoholic liver disease: role of oxidative metabolism. World J Gastroenterol 20:17756–17772. https://doi.org/10.3748/wjg.v20.i47.17756
Centers for Disease Contorl and Prevention (2004) Alcohol-attributable deaths and years of potential life lost--United States, 2001. MMWR Morb Mortal Wkly Rep 53:866–870
Comoglio A, Tomasi A, Malandrino S, Poli G, Albano E (1995) Scavenging effect of silipide, a new silybin-phospholipid complex, on ethanol-derived free radicals. Biochem Pharmacol 50:1313–1316
Feng H, Zheng Y, Chang H, Zhao YH (2017) Study on the protective effect mechanism of total flavones from Prunus cerasifera fruits for alcoholic liver disease in rats. China Pharmacy 28:1332–1337. https://doi.org/10.6039/j.issn.1001-0408.2017.10.10
Gao B, Bataller R (2011) Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology 141:1572–1585. https://doi.org/10.1053/j.gastro.2011.09.002
Gufford BT, Barr JT, González-Pérez V, Layton ME, White JRJ, Oberlies NH, Paine MF (2015) Quantitative prediction and clinical evaluation of an unexplored herb-drug interaction mechanism in healthy volunteers. CPT Pharmacometrics Syst Pharmacol 4:701–710. https://doi.org/10.1002/psp4.12047
Huang Q, Shi J, Gao B, Zhang HY, Fan J, Li XJ, Fan JZ, Zhang JK (2015) Gastrodin: an ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species. Bone 73:132–144. https://doi.org/10.1016/j.bone.2014.12.059
Jiang ZH, Chen C, Wang J, Xie WY, Wang M, Li XP, Zhang XY (2016) Purple potato (Solanum tuberosum L.) anthocyanins attenuate alcohol-induced hepatic injury by enhancing antioxidant defense. J Nat Med 70:45–53. https://doi.org/10.1007/s11418-015-0935-3
Ji W, Zhang M, Wang D, Wang X, Liu J, Huang L (2015) Superhydrophilic molecularly imprinted polymers based on a water-soluble functional monomer for the recognition of gastrodin in water media. J Chromatogr A 1425:88–96. https://doi.org/10.1016/j.chroma.2015.11.053
Kalthoff S, Ehmer U, Freiberg N, Manns MP, Strassburg CP (2010) Interaction between oxidative stress sensor Nrf2 and xenobiotic-activated aryl hydrocarbon receptor in the regulation of the human phase II detoxifying UDP-glucuronosyltransferase 1A10. J Biol Chem 285:5993–6002. https://doi.org/10.1074/jbc.M109.075770
Kensler TW, Wakabayashi N, Biswal S (2007) Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu Rev Pharmacol Toxicol 47:89–116. https://doi.org/10.1146/annurev.pharmtox.46.120604.141046
Kumar H, Kim IS, More SV, Kim BW, Bahk YY, Choi DK (2013) Gastrodin protects apoptotic dopaminergic neurons in a toxin-induced Parkinson's disease model. Evid Based Complement Alternat Med 2013:514095. https://doi.org/10.1155/2013/514095
Li HL, Wang XB, Liu M, Feng YB, Zhang QF (2015) Protective effects of NYG-1 on CCL4-induced acute liver injury in rats. Chin J Pharm Toxicol 29:59
Jiang B, Cai F, Gao SH, Meng LY, Liang FY, Dai X, Xu W, Chen WS (2012) Induction of cytochrome P450 3A by Shexiang Baoxin Pill and its main components. Chem Biol Interact 195:105–113. https://doi.org/10.1016/j.cbi.2011.12.001
Luo M, Zhao A, Li J, Chen Y, Tian D, Wang C, Hu Z, Gao J (2015) Acute liver injury attenuation of a novel recombinant sTNFR through blocking hepatic apoptosis. Immunopharmacol Immunotoxicol 37:295–300. https://doi.org/10.3109/08923973.2015.1035390
Luper S (1998) A review of plants used in the treatment of liver disease: part 1. Altern Med Rev 3:410–421
Mani V, Arivalagan S, Siddique AI, Namasivayam N (2016) Antioxidant and anti-inflammatory role of zingerone in ethanol-induced hepatotoxicity. Mol Cell Biochem 421:169–181. https://doi.org/10.1007/s11010-016-2798-7
Park JW, Shin NR, Shin IS, Kwon OK, Kim JS, Oh SR, Kim JH, Ahn KS (2016) Silibinin inhibits neutrophilic inflammation and mucus secretion induced by cigarette smoke via suppression of ERK-SP1 pathway. Phytother Res 30:1926–1936. https://doi.org/10.1002/ptr.5686
Qu LL, Yu B, Li Z, Jiang WX, Jiang JD, Kong WJ (2016) Gastrodin ameliorates oxidative stress and proinflammatory response in nonalcoholic fatty liver disease through the AMPK/Nrf2 pathway. Phytother Res 30:402–411. https://doi.org/10.1002/ptr.5541
Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J (2009) Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 373:2223–2233. https://doi.org/10.1016/S0140-6736(09)60746-7
Salomone F, Barbagallo I, Godos J, Lembo V, Currenti W, Cinà D, Avola R, D'Orazio N, Morisco F, Galvano F, Li Volti G (2017) Silibinin restores NAD+ levels and induces the SIRT1/AMPK pathway in non-alcoholic fatty liver. Nutrients 9:pii 9:E1086. https://doi.org/10.3390/nu9101086
Singh M, Kapoor A, Bhatnagar A (2015) Oxidative and reductive metabolism of lipid-peroxidation derived carbonyls. Chem Biol Interact 234:261–273. https://doi.org/10.1016/j.cbi.2014.12.028
Strolin Benedetti M, Whomsley R, Baltes E (2006) Involvement of enzymes other than CYPs in the oxidative metabolism of xenobiotics. Expert Opin Drug Metab Toxicol 2:895–921. https://doi.org/10.1517/17425255.2.6.895
Sultana B, Yaqoob S, Zafar Z, Bhatti HN (2018) Escalation of liver malfunctioning: a step toward herbal awareness. J Ethnopharmacol 216:104–119. https://doi.org/10.1016/j.jep.2018.01.002
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84. https://doi.org/10.1016/j.biocel.2006.07.001
Wang M, Sun J, Jiang Z, Xie W, Zhang X (2015) Hepatoprotective effect of kaempferol against alcoholic liver injury in mice. Am J Chin Med 43:241–254. https://doi.org/10.1142/S0192415X15500160
Wu YH, Hao BJ, Shen E, Meng QL, Hu MH, Zhao Y (2012) Protective properties of Laggera alata extract and its principle components against d-galactosamine-injured hepatocytes. Sci Pharm 80:447–456. https://doi.org/10.3797/scipharm.1108-16
Xiao MM, Zhang YQ, Wang WT, Han WJ, Lin Z, Xie RG, Cao Z, Lu N, Hu SJ, Wu SX, Dong H, Luo C (2016) Gastrodin protects against chronic inflammatory pain by inhibiting spinal synaptic potentiation. Sci Rep 6:37251. https://doi.org/10.1038/srep37251
Xu G, Huang K, Zhou J (2018) Hepatic AMP kinase as a potential target for treating nonalcoholic fatty liver disease: evidence from studies of natural products. Curr Med Chem 25:889–907. https://doi.org/10.2174/0929867324666170404142450
Yang XW, Yao WJ, Shi HT, Liu HL, Li YF, Gao YB, Liu RH, Xu LP (2016) Paeoniflorin protects Schwann cells against high glucose induced oxidative injury by activating Nrf2/ARE pathway and inhibiting apoptosis. J Ethnopharmacol 185:361–369. https://doi.org/10.1016/j.jep.2016.03.031
Zhao S, Li N, Zhen Y, Ge M, Li Y, Yu B, He H, Shao RG (2015) Protective effect of gastrodin on bile duct ligation-induced hepatic fibrosis in rats. Food Chem Toxicol 86:202–207. https://doi.org/10.1016/j.fct.2015.10.010
Zhi X, Ding SQ, Shen YF (2014) Silibinin activates AMP-activated protein kinase to protect neuronal cells from oxygen and glucose deprivation-re-oxygenation. Biochem Biophys Res Commun 454:313–319. https://doi.org/10.1016/j.bbrc.2014.10.080
Funding
This work was supported by Construction Project of Shaanxi Collaborative Innovation Center/Qinling-Bashan Mountains Bioresources Comprehensive Development and Collaborative Innovation (QBXT-Z(Z)-15-1, QBXT-Z(Z)-15-21), the High-end Foreign Experts Recruitment Program of State Administration of Foreign Experts Affairs (GDT20176100048, GDT20186100426), Shaanxi Science and Technology Coordinating Innovation Engineering Program (2015KTTSSF01-03, 2015HBGC-18), Shaanxi Provincial Science and Technology Research Development Program (2017NY180), Shaanxi Province Key Research and Development Plan (2017SF-074), The Scientific Research Program of the Shaanxi Provincial Education Department (17JK0135), and Shaanxi University of Technology Master Graduate Innovation Project (SLGYCX1833).
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All animal experimental protocols were reviewed and approved by the Ethics Committee of Shaanxi University of Technology for the use of laboratory animals.
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Li, XX., Jiang, ZH., Zhou, B. et al. Hepatoprotective effect of gastrodin against alcohol-induced liver injury in mice. J Physiol Biochem 75, 29–37 (2019). https://doi.org/10.1007/s13105-018-0647-8
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DOI: https://doi.org/10.1007/s13105-018-0647-8