Insights into the anorexic mechanism of Khat:an integrated in vivo,ex vivo,and in silico investigations  

作　　者：Ahmed Ali Jerah Manal Mohamed Elhassan Taha Abdullah Farasani Sivakumar Sivagurunathan Moni Emad Sayed Shaheen Andleeb Khan Ibrahim Abdo Khardali Magbool Oraiby Heyam Mohamed Ali Sidahmed Siddig Ibrahim Abdelwahab 

机构地区：[1]Department of Medical Laboratory Technology,College of Applied Medical Sciences,Jazan University,Jazan 45142,Saudi Arabia [2]Health Research Centre,Jazan University,Jazan 45142,Saudi Arabia [3]Department of Pharmaceutics,College of Pharmacy,Jazan University,Jazan 45142,Saudi Arabia [4]Department of Biosciences,Faculty of Science,Integral University,Lucknow 226026,India [5]Poison Control and Medical Forensic Chemistry Center,General Directorate of Health Affairs,Jazan 45142,Saudi Arabia [6]Department of Pharmaceutical Chemistry,Faculty of Pharmacy,Al-Neelain University,Khartoum 16458,Sudan

出　　处：《Traditional Medicine Research》2024年第10期36-51,共16页TMR传统医学研究

基　　金：The authors extend their appreciation to the Deputyship for Research&Innovation,Ministry of Education in Saudi Arabia,for funding this research work through project number ISP23-82.

摘　　要：Background:Chewing Khat(Catha edulis)releases cathine and cathinone,which may reduce appetite via an unknown mechanism.This study investigated the peripheral and central effects of fresh leaves and buds of Catha edulis water extract(CEWE)on appetite biomarkers,gene expression,and body weight,using in vivo,ex vivo,and in silico models.Methods:Rats of both sexes were orally administered CEWE at different doses and durations in three different experiments.Liquid chromatography-mass spectroscopy(LC-MS)-MS was used to detect cathinone and cathine in the murine blood.The effect of Khat on serotonin receptors was studied in isolated rat fundus samples.Docking of the two Khat ligands was performed on G(The 5-hydroxytryptamine-type 2C receptor(5-HT2C)in an agonist-bound active conformation)and H(5-HT2C in an antagonist-bound inactive conformation)proteins to determine which ligands are most likely to act as agonists or antagonists.Results:Significant differences(P<0.05)in body weight were observed between the CEWE-treated groups and the controls over eight weeks.However,the plasma leptin and ghrelin levels did not change significantly(P>0.05).The expression of the ghrelin and leptin genes was also unaffected,but the expression of the 5-hydroxytryptamine(5-HT)gene decreased(P<0.05)with CEWE treatment.CEWE antagonizes 5-HT receptors in isolated rat fundus samples.Docking findings indicated that the khat ligands bound to 5-HT2C receptors.Cathine and cathinone levels in rat plasma were measured.Conclusion:Khat extract may suppress appetite by antagonizing the 5-HT receptors.Further research is required to understand its mechanism and potential applications.

关 键 词：Catha edulis APPETITE LEPTIN GHRELIN 5-HYDROXYTRYPTAMINE molecular docking 

分 类 号：R-332[医药卫生]