Qichao Wang1, Rui Wen2, Qinghua Lin3, Na Wang1, Ping Lu1, Xianmin Zhu4. 1. Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China. 2. Department of Resources Science of Traditional Chinese Medicines, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. 3. Department of Natural Medicinal Chemistry, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. 4. Translational Center for Stem Cell Research, Tongji Hospital, Department of Regenerative Medicine, Tongji University School of Medicine, Shanghai, 200065, China. xianminzhu@hotmail.com.
Abstract
BACKGROUD: Wogonoside (WO), a flavonoid extracted from Huangqin, plays multiple physiological roles. However, it has remained elusive how WO regulates hepatic fibrogenesis until now. AIM: The purpose of the study was to investigate the potential protective effects of WO against liver fibrosis induced by carbon tetrachloride (CCl4). METHODS: In this study, male rats were randomly allocated into four groups: a control group, the CCl4 group, the CCl4 and WO (4 mg/kg) group, and CCl4 and WO (8 mg/kg) group. Hepatic fibrosis was induced by subcutaneous injection of CCl4 twice a week for a continuous 6-week period. Then the rats were intragastrically administrated with WO daily for 4 weeks before being killed. RESULTS: As expected, histopathological assessment, Masson trichrome staining, and Sirius red staining demonstrated that WO drastically ameliorated the hepatic fibrosis caused by CCl4. WO significantly attenuated the CCl4-induced upregulations of liver indices including alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin-1β, IL-6, hexadecenoic acid and laminin in serum, as well as hydroxyproline, malondialdehyde and phosphatidylinositol 3-kinase (PI3K)/protein Kinase B(Akt)/mechanistic target of rapamycin (mTOR)/nuclear factor-kappa B signalings in liver. Meanwhile, WO also effectively recovered the depletions of superoxide dismutase, glutathione and IL-10. Furthermore, we evaluated the effects of WO on the alpha smooth muscle actin, type I collagen expressions, and PI3K/Akt/ mTOR/ribosomal protein S6 kinase 70 kDa (p70S6K) signaling in transforming growth factor (TGF-β) stimulated hepatic stellate cell-T6 cells. CONCLUSIONS: These results suggested that WO had significant protective effects against liver fibrosis induced by CCl4.
BACKGROUD: Wogonoside (WO), a flavonoid extracted from Huangqin, plays multiple physiological roles. However, it has remained elusive how WO regulates hepatic fibrogenesis until now. AIM: The purpose of the study was to investigate the potential protective effects of WO against liver fibrosis induced by carbon tetrachloride (CCl4). METHODS: In this study, male rats were randomly allocated into four groups: a control group, the CCl4 group, the CCl4 and WO (4 mg/kg) group, and CCl4 and WO (8 mg/kg) group. Hepatic fibrosis was induced by subcutaneous injection of CCl4 twice a week for a continuous 6-week period. Then the rats were intragastrically administrated with WO daily for 4 weeks before being killed. RESULTS: As expected, histopathological assessment, Masson trichrome staining, and Sirius red staining demonstrated that WO drastically ameliorated the hepatic fibrosis caused by CCl4. WO significantly attenuated the CCl4-induced upregulations of liver indices including alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor-α, interleukin-1β, IL-6, hexadecenoic acid and laminin in serum, as well as hydroxyproline, malondialdehyde and phosphatidylinositol 3-kinase (PI3K)/protein Kinase B(Akt)/mechanistic target of rapamycin (mTOR)/nuclear factor-kappa B signalings in liver. Meanwhile, WO also effectively recovered the depletions of superoxide dismutase, glutathione and IL-10. Furthermore, we evaluated the effects of WO on the alpha smooth muscle actin, type I collagen expressions, and PI3K/Akt/ mTOR/ribosomal protein S6 kinase 70 kDa (p70S6K) signaling in transforming growth factor (TGF-β) stimulated hepatic stellate cell-T6 cells. CONCLUSIONS: These results suggested that WO had significant protective effects against liver fibrosis induced by CCl4.
Authors: Lin Luo; Adam A Wall; Jeremy C Yeo; Nicholas D Condon; Suzanne J Norwood; Simone Schoenwaelder; Kaiwen W Chen; Shaun Jackson; Brendan J Jenkins; Elizabeth L Hartland; Kate Schroder; Brett M Collins; Matthew J Sweet; Jennifer L Stow Journal: Nat Commun Date: 2014-07-15 Impact factor: 14.919
Authors: Erwin Gäbele; Shimon Reif; Shigeki Tsukada; Ramon Bataller; Yutaka Yata; Terry Morris; Laura W Schrum; David A Brenner; Richard A Rippe Journal: J Biol Chem Date: 2005-01-26 Impact factor: 5.157