title: Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin.
abstract: Geniposide (GE) is the main bioactive component of Gardeniae Fructus. The hepatotoxicity of geniposide limited clinical application. In order to get a new geniposide derivative that has less hepatotoxicity and still possesses the antidepressant activity, a new C-1 hydroxyl methylation derivative named methyl genipin (MG) was synthesized from geniposide. In the present study, we demonstrated that MG did not increase the liver index, alanine aminotransferase (ALT) and aspirate aminotransferase (AST). Histopathological examination suggested that no toxic damages were observed in rats treated orally with MG (0.72 mmol/kg). More importantly, a 7-day treatment with MG at 0.13, 0.26, and 0.52 mmol/kg/day could reduce the duration of immobility. It showed that the antidepressant-like effects of MG were similar to GE in the tail suspension test and the forced swim test. Furthermore, we found MG could be detected in the brain homogenate of mice treated orally with MG 0.52 mmol/kg/day for 1 day by HPLC. The area under the curve (AUC) of MG in the brain homogenate was enhanced to 21.7 times that of GE. The brain amount and distribution speed of MG were improved significantly after oral administration. This study demonstrated that MG possessed the antidepressant effects and could cross the blood-brain barrier, but had less hepatotoxicity.
authors.affiliation: School of Pharmacy, Yantai University, Yantai 264005, China. 13792527062@163.com.|Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Yantai 264005, China. 13792527062@163.com.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China. 13792527062@163.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Che
authors.affiliation: School of Pharmacy, Yantai University, Yantai 264005, China. wangmei123yu@163.com.|Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Yantai 264005, China. wangmei123yu@163.com.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China. wangmei123yu@163.com.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Yantai University, Yantai 264005, China. bluewangtian@hotmail.com.|Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Yantai 264005, China. bluewangtian@hotmail.com.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China. bluewangtian@hotmail.com.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Yantai University, Yantai 264005, China. katiefhydong@sina.com.|Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Yantai 264005, China. katiefhydong@sina.com.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China. katiefhydong@sina.com.
authors.forename: Huaying
authors.initials: H
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Yantai University, Yantai 264005, China. mingyan-123456@163.com.|Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Yantai 264005, China. mingyan-123456@163.com.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China. mingyan-123456@163.com.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Yang
authors.affiliation: School of Pharmacy, Yantai University, Yantai 264005, China. wangwenyan@luye.cn.|Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Yantai 264005, China. wangwenyan@luye.cn.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China. wangwenyan@luye.cn.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Yantai University, Yantai 264005, China. xuhui33@sina.com.|Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Yantai 264005, China. xuhui33@sina.com.|Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai 264005, China. xuhui33@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D039823:Iridoids / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D015394:Molecular Structure; D010539:Permeability; D051381:Rats; D014018:Tissue Distribution
chemical_list: D000928:Antidepressive Agents; D039823:Iridoids; C007835:geniposide; C007834:genipin
keywords: antidepressant effect; blood–brain barrier; geniposide derivative; hepatotoxicity