title: Protective effects of hepatocyte-specific glycyrrhetic derivatives against carbon tetrachloride-induced liver damage in mice.
abstract: Glycyrrhetic acid (GA), the main hydrolysate of glycyrrhizic acid extracted from the roots of the Chinese herb Glycyrrhiza glabra, was reported to be accumulated in hepatocytes due to the extensive distribution of GA receptors in liver. A series of hepatocyte-specific derivatives on the basis of anetholtrithione and glycyrrhizic were designed and synthesized. The potential beneficial effect was evaluated in carbon tetrachloride (CCl4)-induced liver injury model. In addition, the hepatoprotective activity of these derivatives was assessed by measuring levels of serum marker enzymes, including serum glutamate oxaloacetate transaminase (GOT), serum glutamate pyruvate transaminase (GPT), alkaline phosphatase (AKP), lactate dehydrogenase (LDH) and the ratio of GSH to GSSG. Gratifyingly, compounds 5a-c (100mg/kg, p.o.) markedly prevented CCl4-induced elevation of levels of serum GPT, GOT. A comparative histopathological study of liver exhibited almost a normal liver lobular architecture and cell structure of the livers, as compared to CCl4-treated group. These findings were confirmed with the histopathological observations, where hepatocyte-specific glycyrrhetic acid derivatives 5a-c were capable of reversing the toxic effects of CCl4on hepatocytes.
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center of Drug Discovery, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Yang
authors.affiliation: Center of Drug Discovery, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Yaodan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Center of Drug Discovery, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China.
authors.forename: Pan
authors.initials: P
authors.lastname: Chen
authors.affiliation: Center of Drug Discovery, Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: zhanghb80@163.com.
authors.forename: Huibin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, PR China. Electronic address: jpzhou668@163.com.
authors.forename: Jinpei
authors.initials: J
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006034:Glycyrrhetinic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D002251:Carbon Tetrachloride; D006034:Glycyrrhetinic Acid
keywords: Anethol trithione; Glycyrrhetic acid; Hepatic injury; Hepatoprotective