Cargando…

Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin

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 nam...

Descripción completa

Detalles Bibliográficos
Autores principales: Che, Xin, Wang, Meiyu, Wang, Tian, Fan, Huaying, Yang, Mingyan, Wang, Wenyan, Xu, Hui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273916/
https://www.ncbi.nlm.nih.gov/pubmed/27438811
http://dx.doi.org/10.3390/molecules21070923
_version_ 1783377497281265664
author Che, Xin
Wang, Meiyu
Wang, Tian
Fan, Huaying
Yang, Mingyan
Wang, Wenyan
Xu, Hui
author_facet Che, Xin
Wang, Meiyu
Wang, Tian
Fan, Huaying
Yang, Mingyan
Wang, Wenyan
Xu, Hui
author_sort Che, Xin
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6273916
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62739162018-12-28 Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin Che, Xin Wang, Meiyu Wang, Tian Fan, Huaying Yang, Mingyan Wang, Wenyan Xu, Hui Molecules Article 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. MDPI 2016-07-16 /pmc/articles/PMC6273916/ /pubmed/27438811 http://dx.doi.org/10.3390/molecules21070923 Text en © 2016 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Che, Xin
Wang, Meiyu
Wang, Tian
Fan, Huaying
Yang, Mingyan
Wang, Wenyan
Xu, Hui
Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin
title Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin
title_full Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin
title_fullStr Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin
title_full_unstemmed Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin
title_short Evaluation of the Antidepressant Activity, Hepatotoxicity and Blood Brain Barrier Permeability of Methyl Genipin
title_sort evaluation of the antidepressant activity, hepatotoxicity and blood brain barrier permeability of methyl genipin
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6273916/
https://www.ncbi.nlm.nih.gov/pubmed/27438811
http://dx.doi.org/10.3390/molecules21070923
work_keys_str_mv AT chexin evaluationoftheantidepressantactivityhepatotoxicityandbloodbrainbarrierpermeabilityofmethylgenipin
AT wangmeiyu evaluationoftheantidepressantactivityhepatotoxicityandbloodbrainbarrierpermeabilityofmethylgenipin
AT wangtian evaluationoftheantidepressantactivityhepatotoxicityandbloodbrainbarrierpermeabilityofmethylgenipin
AT fanhuaying evaluationoftheantidepressantactivityhepatotoxicityandbloodbrainbarrierpermeabilityofmethylgenipin
AT yangmingyan evaluationoftheantidepressantactivityhepatotoxicityandbloodbrainbarrierpermeabilityofmethylgenipin
AT wangwenyan evaluationoftheantidepressantactivityhepatotoxicityandbloodbrainbarrierpermeabilityofmethylgenipin
AT xuhui evaluationoftheantidepressantactivityhepatotoxicityandbloodbrainbarrierpermeabilityofmethylgenipin