Ethyl Acetate Fraction of Amomum xanthioides Exerts Antihepatofibrotic Actions via the Regulation of Fibrogenic Cytokines in a Dimethylnitrosamine‐Induced Rat Model

Abstract

Amomum xanthioides has been traditionally used to treat diverse digestive system disorders in the Asian countries. We investigated antihepatofibrotic effects of ethyl acetate fraction of Amomum xanthioides (EFAX). Liver fibrosis is induced by dimethylnitrosamine (DMN) injection (intraperitoneally, 10 mg/kg of DMN for 4 weeks to Sprague-Dawley rats). EFAX (25 or 50 mg/kg), silymarin (50 mg/kg), or distilled water was orally administered every day. The DMN injection drastically altered body and organ mass, serum biochemistry, and platelet count, while EFAX treatment significantly attenuated this alteration. Severe liver fibrosis is determined by trichrome staining and measurement of hydroxyproline contents. EFAX treatment significantly attenuated these symptoms as well as the increase in oxidative by-products of lipid and protein metabolism in liver tissues. DMN induced a dramatic activation of hepatic stellate cells and increases in the levels of protein and gene expression of transforming growth factor-beta (TGF-β), platelet derived growth factor-beta (PDGF-β), and connective tissue growth factor (CTGF). Immunohistochemical analyses revealed increases in the levels of protein and gene expression of α-smooth muscle actin. These alterations were significantly normalized by EFAX treatment. Our findings demonstrate the potent antihepatofibrotic properties of EFAX via modulation of fibrogenic cytokines, especially TGF-β in the liver fibrosis rat model.

Ethyl Acetate Fraction of Amomum xanthioides Ameliorates Nonalcoholic Fatty Liver Disease in a High-Fat Diet Mouse Model

“…Prolonged inflammation in the liver could progress into hepatic fibrosis, cirrhosis, and sometimes hepatocarcinoma which determine liver disorder-related mortality [49]. Our previous studies presented anti-hepatofibrotic effects of EFAX using bile-duct ligation and DMN liver injury animal models [21,22]; however, this study first reports the therapeutic effects of EFAX against NAFLD.…”

“…To confirm the reproducibility of the EFAX chemical composition, ultrahigh-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS, Thermo Scientific, Waltham, CA, USA) was performed as described previously [ 21 ]. Briefly, quantitative analysis of the major three compounds in EFAX was performed using UHPLC-MS/MS.…”

“…Amomum xanthioides is a medicinal herb that has been reported to show gastrointestinal protection, liver protective, and anti-dyslipidemic effects [ 20 ]. Moreover, our previous studies proved that one A. xanthioides fraction has anti-hepatofibrotic activity in dimethylnitrosamine (DMN) and bile duct-ligation animal models [ 21 , 22 ]. Hepatic fibrosis is considered an advanced pathologic stage of NAFLD [ 13 ].…”

Treatment Efficiency of Different Routes of Bone Marrow-Derived Mesenchymal Stem Cell Injection in Rat Liver Fibrosis Model

“…Activated HSCs secrete TGF-β1 and CTGF to achieve their auto-activation [18]. TGF-β1 is a primary agent in the liver fibrogenic response, which is the result of an imbalance between ECM synthesis and degradation with the overproduction of ECM components [19].…”

Anti-Inflammatory Effect of <i>o</i>-Vanillic Acid on Lipopolysaccharide-Stimulated Macrophages and Inflammation Models

“…Amomum xanthoides is a traditional herbal medicine used across Asia for treatment of digestive system disorders [11]. Many studies have reported its pharmacological effects such as anti-allergy and anti-inflammatory activities [12,13]. Furthermore, several studies have indicated the anti-inflammatory effect of the active components in Amomum xanthoides, such as vanillic acid, tyrosol, and 1,2,4,5-tetramethoxybenxene [13,14].…”