Journal of Ethnopharmacology 135 (2011) 344–350 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm An herbal fruit, Amomum xanthoides, ameliorates thioacetamide-induced hepatic fibrosis in rat via antioxidative system Jing-Hua Wang, Jang-Woo Shin, Min-Kyung Choi, Hyeong-Geug Kim, Chang-Gue Son ∗ Liver and Immunology Research Center, Institute of Traditional Medicine and Bioscience of Daejeon University, 22-5 Daeheung-dong Jung-gu, Daejeon 301-704, Republic of Korea article info Article history: Received 22 November 2010 Received in revised form 28 February 2011 Accepted 9 March 2011 Available online 16 March 2011 Keywords: Amomum xanthoides Methanol fraction Oxidative stress Antifibrosis Hepatoprotective Antioxidative abstract Aim of the study: Amomum xanthoides is a well-known traditional herbal medicine mainly for diverse digestive system disorders in Asia for a long time. In the present study, we investigate the effects and action mechanism of methanol fraction of Amomum xanthoides (MFAX) on thioacetamide (TAA)-induced liver fibrosis in rat model. Materials and methods: TAA (200 mg/kg, ip on twice a week for 14 weeks) treated rats were orally administered with MFAX (25, 50 or 100 mg/kg) once a day from the 7th week until 14th week. Result: Significantly elevated serum bilirubin, liver tissue hydroxyproline and malondialdehyde (MDA) in liver fibrosis were ameliorated by MFAX treatment. Further, MFAX treatment attenuated the reactive oxygen species (ROS) levels and restored glutathione (GSH) content and glutathione-peroxidase (GPx) activity. Histopathological data showed that MFAX treatment inhibited collagen accumulation and acti- vation of hepatocyte stellate cells (HSCs) in the liver tissue. Compared to the TAA group, activation of inducible nitric oxide synthase (iNOS), tumor necrosis factor alpha (TNF-), transforming growth factor beta (TGF-), platelet-derived growth factor beta (PDGF-) mRNAs and the level of pro-fibrotic cytokines PDGF- and connective tissue growth factor (CTGF) in the liver tissue were attenuated in MFAX treated groups. Conclusion: The above evidences collectively indicate that MFAX is a potential herb which can be used as an anti-hepatofibrotic remedy. © 2011 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Amomi Fructus is a traditional medicinal herb in Asia which has been used extensively for digestive system disorders for two thou- sand years. According to the traditional Chinese medicine (TCM) Abbreviations: ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; CTGF, connective tissue growth factor; DAB, diaminoben- zidine; DDB, dimethyl dimethoxy biphenyl dicarboxylate; DEPPD, N,N-diethyl- para-phenylendiamine sulfate; DTNB, 5,5-dithiobis-(2-nitrobenzoic acid); ECM, extracellular matrix; GPx, glutathione peroxidase; GSH, glutathione; H2O2, hydro- gen peroxide; HCl, hydrochloric acid; HPTLC, high performance thin layer chromatography; HSCs, hepatic stellate cells; iNOS, inducible nitric oxide synthase; KCl, potassium chloride; MDA, malondialdehyde; MFAX, methanol soluble frac- tion of Amomum xanthoides; PDGF-, platelet-derived growth factor-beta; PFAX, petroleum ether soluble fraction of Amomum xanthoides; QOL, quality of life; ROS, reactive oxygen species; SOD, superoxide dismutase; SPF, specific pathogen-free; TAA, thioacetamide; TBA, thiobarbituric acid; TEP, 1,1,3,3-tetraethoxypropane; TGF- , transforming growth factor-beta; TNF-, tumor necrosis factor-alpha; -SMA, alpha-smooth muscle actin; -NADPH, -nicotinamide adenine dinucleotide phos- phate. ∗ Corresponding author at: Liver and Immunology Research Center, Daejeon Oriental Hospital of Daejeon University, 22-5 Daeheung-dong Jung-gu, Daejeon 301-704, Republic of Korea. Tel.: +82 42 229 6723; fax: +82 42 257 6398. E-mail address: ckson@dju.ac.kr (C.-G. Son). theory, liver-Qi is easy to stagnate, and Amomi Fructus has a strong function of promoting the circulation of Qi. Therefore, many tradi- tional hepatotherapeutic formulas in TCM contain Amomi Fructus as an indispensable ingredient (Wang et al., 2010b).Generally, Amomi Fructus is a dried ripe fruit of Amomum xanthoides WALL, Amomum villosum LOUR or Amomum longiligulare T.L. Wu. Amomi Fructus belongs to the Zingiberaceae family, grows in tropical and subtropical regions (Pharmacopoeia of China, 1995). Amomi Fructus contains five main classes of chemical components includ- ing volatile oil (approximately 1.7–3%), saponins (approximately 0.69%), flavonoid glycosides, organic acids and inorganic compo- nents (Sun et al., 2002; Hu et al., 2005). Previous studies reported many pharmaceutical activities of Amomi Fructus in experimen- tal models, hypoglycemic effect on diabetes (Park and Park, 2001; Kwon et al., 2003), improvement gastrointestinal motility (Zhu et al., 2001; Zhu et al., 2006), antioxidative effect (Guo et al., 2008), analgesic and anti-inflammatory effect (Wu et al., 2004), etc. On the other hand, most of chronic liver injuries including alcoholic disorder, viral hepatitis, biliary obstruction, or hemochro- matosis consequently lead to hepatic fibrosis, a critical step deciding clinical outcome of chronic liver diseases (Friedman, 2003; Kung et al., 2008). Typical mechanism of liver fibrosis is explicated by a continuous insult to hepatocytes and Kupffer cells followed by 0378-8741/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2011.03.026