Lili Zhu1, Lei Wang2, Fei Cao3, Peng Liu3, Haidong Bao4, Yumei Yan5, Xin Dong3, Dong Wang6, Zhongyu Wang3, Peng Gong3. 1. Department of Gynaecology and Obstetrics, The First Affiliated Hospital of Dalian Medical University, Dalian, China. 2. Department of Anesthesiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China. 3. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Dalian Medical University, 222 Zhongshan Road, Dalian 116011, China. 4. Department of Gastrointestinal Endoscopy, The First Affiliated Hospital of Dalian Medical University, Dalian, China. 5. Department of Ultrasound, The First Affiliated Hospital of Dalian Medical University, Dalian, China. 6. Department of Hepatobiliary Surgery, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, China.
Abstract
BACKGROUND: The purpose of the present study was to investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). METHODS: Rats received vehicle or CA (20, 50, or 100 mg/kg per day) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR and western blot. RESULTS: After BDL, plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology. Hepatic uptake transporters (Ntcp, Oatp 1a4, and Oatp 1b2) were downregulated, while efflux transporters (Bsep and Mrp 2/3/4) were upregulated. BDL inhibited the expressions of Cyp7a1, Cyp8b1, and Cyp27a1 and induced Ugt1a1. CA treatment decreased ALT, AST, TBIL, and TBA (P < 0.05) and alleviated the liver pathological changes. The degree of expression changes in the transporters and enzymes was extended by CA (P < 0.05). SIRT1 protein was induced after CA treatment in BDL rats. CONCLUSIONS: Chlorogenic acid attenuated hepatotoxicity and cholestasis by decreasing the uptake and synthesis of bilirubin and bile acids and accelerating the metabolism and efflux of bilirubin and bile acids.
BACKGROUND: The purpose of the present study was to investigate the effect and potential mechanism of chlorogenic acid (CA) on liver injury induced by cholestasis in a rat model of bile duct ligation (BDL). METHODS:Rats received vehicle or CA (20, 50, or 100 mg/kg per day) orally for 3 days. On the 4th day, the rats underwent sham or BDL surgery, and were orally administrated vehicle or CA for 3 or 7 days. mRNA and protein expression levels were evaluated by qRT-PCR and western blot. RESULTS: After BDL, plasma levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and total bile acids (TBA) were increased and typical pathological changes were observed in liver morphology. Hepatic uptake transporters (Ntcp, Oatp 1a4, and Oatp 1b2) were downregulated, while efflux transporters (Bsep and Mrp 2/3/4) were upregulated. BDL inhibited the expressions of Cyp7a1, Cyp8b1, and Cyp27a1 and induced Ugt1a1. CA treatment decreased ALT, AST, TBIL, and TBA (P < 0.05) and alleviated the liver pathological changes. The degree of expression changes in the transporters and enzymes was extended by CA (P < 0.05). SIRT1 protein was induced after CA treatment in BDL rats. CONCLUSIONS:Chlorogenic acid attenuated hepatotoxicity and cholestasis by decreasing the uptake and synthesis of bilirubin and bile acids and accelerating the metabolism and efflux of bilirubin and bile acids.
Authors: Emil Paluch; Piotr Okińczyc; Anna Zwyrzykowska-Wodzińska; Jakub Szperlik; Barbara Żarowska; Anna Duda-Madej; Przemysław Bąbelewski; Maciej Włodarczyk; Wioleta Wojtasik; Robert Kupczyński; Antoni Szumny Journal: Molecules Date: 2021-12-08 Impact factor: 4.411