Preparation and Antidepressant Activity Study of β-sitosterol and Its Derivatives from the Fruit of Sorbus pohuashanensis
- VernacularTitle:百花花楸果中β-谷甾醇及其衍生物的制备及抗抑郁活性研究
- Author:
Xiaofeng LIU
1
;
Xinyuan CAO
1
;
Yongxia YIN
2
;
Bo WANG
1
;
Wenhua HUANG
1
Author Information
1. Dept. of Pharmacy，Ningxia Hui Autonomous Region People’s Hospital，Yinchuan 750002，China
2. Chinese Medicine Material College，Jilin Agricultural University，Changchun 130118，China
- Publication Type:Journal Article
- Keywords:
Fruit of Sorbus pohuashanensis;
β-sitosterol;
Derivative;
Antidepressant activities
- From:
China Pharmacy
2021;32(1):64-70
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE： To prepare β-sitosterol （shorted fo r “Sit”） and its deri vatives from the fruit of Sorbus pohuashanensis，and to investigte their antidepressant activities. METHODS ：Using the fruit of S. pohuashanensis as raw material ， extracted with 75％ ethanol and 20％KOH solution ，Sit was obtained after extraction and crystallization. C 3 hydroxyl group of Sit was used as the structural modification site ，CH2Cl2 was used as the reaction solvent ，DMAP was used as catalyst ，EDCI was used as dehydrating agent ，4 kinds of organic acids （salicylic acid ，2-tetrahydrofuranic acid ，phenylalanine，sorbic acid ）were added to make the carboxylation reaction to produce ester derivatives Sit-S ，Sit-T，Sit-P and Sit-Sr. The chemical structure of its derivatives were elucidated by IR and NMR. The tail suspension test and the forced swimming model were used to preliminarily explore the antidepressant active components of Sit and 4 kinds of derivatives ；tail suspension test and the spontaneous exercise capacity test were used to screen effective dose of the compounds with antidepressant active. The compound was used alone or in combination with agomelatin [ 40 mg/kg，5-hydroxytryptamine（5-HT）and 5-HT 2C receptor antagonist] ，haloperidol [ 0.2 mg/kg，non-selective D2 receptor antagonist] and bicuculline [ 4 mg/kg，competitive γ-aminobutyric acid（GABA）antagonist]，respectively. Sixty minutes after intraperitoneal injection ，tail suspension test was performed. The levels of 5-HT，dopamine（DA）and GABA in brain tissues of mice were detected by ELISA. The blank control group was given intraperitoneal injection of 10％ propylene glycol solution. RESULTS：By spectrum technology ，the corresponding ester compounds were synthesized by the reaction of Sit with four kinds of organic acids. Among Sit and its four derivatives ，the immobility time of Sit-S group was the shortest in tail suspension test and forced swimming test ，which was significantly shorter than that of blank control group （P＜0.05）. Screening results of Sit-S showed that the effective antidepressant dose was 4 mg/kg， ＊ and it did not affect the spontaneous activity of mice compared with the blank control group （P＞0.05）. With this dose ，Sit-S could significantly shorten the immobility time of mice in tail hua1666@163.com suspension test （P＜0.01），and can s ignificantly increase the ·64levels of 5-HT，DA and GABA in the brain tissue of mice （P＜0.05 or P＜0.01），but its effect can be reversed by agomelatine ， haloperidol and bicuculline to different extent. CONCLUSIONS ：Sit salicylate derivatives Sit-S exhibits good antidepressant activity，and its mechanism of action may be mediated by increasing the levels of 5-HT，DA and GABA.
