PMID- 26019805 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150528 LR - 20201001 IS - 2008-3866 (Print) IS - 2008-3874 (Electronic) IS - 2008-3866 (Linking) VI - 18 IP - 4 DP - 2015 Apr TI - Modulation of IKKbeta/NF-kappaB and TGF-beta1/Smad via Fuzheng Huayu recipe involves in prevention of nutritional steatohepatitis and fibrosis in mice. PG - 404-11 AB - OBJECTIVES: Fuzheng Huayu recipe (FZHY) exerts significant protective effects against liver fibrosis by strengthening the body's resistance and removing blood stasis. However, the molecular mechanisms through which FZHY affects liver fibrosis are still unclear. In this study, we examined the expression levels of factors involved in the inhibitor kappaB kinase-beta (IKK-beta)/nuclear factor-kappaB (NF-kappaB) and transforming growth factor beta 1 (TGF-beta1)/Smad signaling pathways to elucidate whether FZHY could attenuate nutritional steatohepatitis and fibrosis in mice. MATERIALS AND METHODS: C57BL/6J mice were fed with methionine-choline deficient (MCD) diet for 8 weeks to induce fibrotic steatohepatitis. FZHY and/or heme oxygenase-1 (HO-1) chemical inducer (hemin) were administered to mice. The effects of FZHY alone and in combination with hemin were assessed by comparing the severity of hepatic injury, activation of hepatic stellate cells (HSCs), and the expression of oxidative stress, inflammation and fibrogenesis related genes. RESULTS: Administration of FZHY, hemin and FZHY plus hemin significantly ameliorated liver injury. Additionally, our analysis indicated that administration of these agents significantly attenuated oxidative stress, downregulated the expression of pro-inflammatory and pro-fibrotic genes, including IKK-beta, NF-kappaB, monocyte chemoattractant protein-1 (MCP-1), alpha-smooth muscle actin (alpha-SMA), TGF-beta1, Smad3 and Smad4, and upregulated the expression of the antifibrogenic gene Smad7 (P< 0.001). CONCLUSION: FZHY-containing therapies prevented nutritional steatohepatitis and fibrosis through modulating the expression of factors associated with the IKKbeta/NF-kappaB and TGF-beta1/Smad signaling pathways and oxidative stress related genes. FAU - Wang, Rong-Qi AU - Wang RQ AD - Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Mi, Hong-Mei AU - Mi HM AD - Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Li, Hui AU - Li H AD - Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Zhao, Su-Xian AU - Zhao SX AD - Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Jia, Yan-Hong AU - Jia YH AD - Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China. FAU - Nan, Yue-Min AU - Nan YM AD - Department of Traditional and Western Medical Hepatology, Third Hospital of Hebei Medical University, Shijiazhuang, China. LA - eng PT - Journal Article PL - Iran TA - Iran J Basic Med Sci JT - Iranian journal of basic medical sciences JID - 101517966 PMC - PMC4439457 OTO - NOTNLM OT - FuzhengHuayu OT - Heme oxygenase-1 OT - Hepatic fibrosis OT - IKK-beta/NF-kappaB signaling pathway OT - Non-alcoholic steatohepatitis OT - TGF-beta1/Smad signaling pathway COIS- Conflict of interest The authors declared no conflict of interest. EDAT- 2015/05/29 06:00 MHDA- 2015/05/29 06:01 PMCR- 2015/04/01 CRDT- 2015/05/29 06:00 PHST- 2014/06/30 00:00 [received] PHST- 2014/11/24 00:00 [accepted] PHST- 2015/05/29 06:00 [entrez] PHST- 2015/05/29 06:00 [pubmed] PHST- 2015/05/29 06:01 [medline] PHST- 2015/04/01 00:00 [pmc-release] AID - IJBMS-18-404 [pii] PST - ppublish SO - Iran J Basic Med Sci. 2015 Apr;18(4):404-11.