Ziqi Chen1, Fang Liu1, Nanxin Zheng2, Meng Guo1, Leilei Bao3, Yangyang Zhan3, Mingjian Zhang3, Yuanyu Zhao1, Wenyuan Guo4, Guoshan Ding5. 1. Department of Organ Transplantation, ChangZheng Hospital, Second Military Medical University, Shanghai, 200003, China. 2. Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China. 3. National Key Laboratory of Medical Immunology, Second Military Medical University, Shanghai, 200433, China. 4. Department of Organ Transplantation, ChangZheng Hospital, Second Military Medical University, Shanghai, 200003, China. Electronic address: guowenyuan@smmu.edu.cn. 5. Department of Organ Transplantation, ChangZheng Hospital, Second Military Medical University, Shanghai, 200003, China. Electronic address: dingguoshan@smmu.edu.cn.
Abstract
OBJECTIVE: Wuzhi (WZ) capsule contains an ethanol extract of Schisandra sphenanthera. The efficacy of WZ in treating non-alcoholic fatty liver disease (NAFLD) has not yet been elucidated. The present study assessed the effects of WZ on NAFLD. MATERIAL AND METHODS: A C57BL/6 male mouse model of NAFLD was established by feeding the animals a methionine-choline-deficient (MCD) diet. Mice fed the basal diet were used as controls. Both groups were randomly administered WZ or vehicle by gavage for 5 weeks. Body weight change, liver/body weight ratio, metabolic parameters, and histological changes were assessed. Serum levels of IL-1β, IL-6, IL-10, and TNF-α were analysed by ELISA; mRNA expression of these genes in the liver was studied by real-time PCR. Western blotting was used to analyse the protein levels of PPAR-α, PPAR-γ, MCAD, LCAD, and p65 in the liver. RESULTS: After 5 weeks of the MCD diet, the liver/body weight ratio of WZ mice was higher than that of control mice. Liver histology revealed significantly less steatosis, inflammation, and necrosis, which was confirmed by decreased intrahepatic triglycerides and serum ALT in WZ-treated mice. WZ also reduced the liver mRNA expression of IL-1β, IL-6, and TNF-α and the serum levels of IL-1β and IL-6. Sensitivity to steatohepatitis due to WZ administration correlated significantly with alterations in the expression of PPAR-α/γ, as well as the NF-κB signalling pathway. CONCLUSIONS: WZ plays a protective role against MCD-induced steatohepatitis. The underlying mechanism likely involves the upregulation of PPAR-α/γ and downregulation of the NF-κB signalling pathway. Based on its beneficial effects on the liver, WZ is a promising therapeutic for NAFLD patients.
OBJECTIVE: Wuzhi (WZ) capsule contains an ethanol extract of Schisandra sphenanthera. The efficacy of WZ in treating non-alcoholic fatty liver disease (NAFLD) has not yet been elucidated. The present study assessed the effects of WZ on NAFLD. MATERIAL AND METHODS: A C57BL/6 male mouse model of NAFLD was established by feeding the animals a methionine-choline-deficient (MCD) diet. Mice fed the basal diet were used as controls. Both groups were randomly administered WZ or vehicle by gavage for 5 weeks. Body weight change, liver/body weight ratio, metabolic parameters, and histological changes were assessed. Serum levels of IL-1β, IL-6, IL-10, and TNF-α were analysed by ELISA; mRNA expression of these genes in the liver was studied by real-time PCR. Western blotting was used to analyse the protein levels of PPAR-α, PPAR-γ, MCAD, LCAD, and p65 in the liver. RESULTS: After 5 weeks of the MCD diet, the liver/body weight ratio of WZ mice was higher than that of control mice. Liver histology revealed significantly less steatosis, inflammation, and necrosis, which was confirmed by decreased intrahepatic triglycerides and serum ALT in WZ-treated mice. WZ also reduced the liver mRNA expression of IL-1β, IL-6, and TNF-α and the serum levels of IL-1β and IL-6. Sensitivity to steatohepatitis due to WZ administration correlated significantly with alterations in the expression of PPAR-α/γ, as well as the NF-κB signalling pathway. CONCLUSIONS: WZ plays a protective role against MCD-induced steatohepatitis. The underlying mechanism likely involves the upregulation of PPAR-α/γ and downregulation of the NF-κB signalling pathway. Based on its beneficial effects on the liver, WZ is a promising therapeutic for NAFLD patients.