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

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.

Immune Augmentation of Injectable PLGA – Dextran (PLDEX) a Double Polymeric Microspheres as an Adjuvant for Hepatitis B Vaccine

A new method has been developed to prepare microspheres by blending PLGA and dextran polymers (PLDEX) using solvent evaporation technique. Recombinant hepatitis B vaccine (HBsAg) was incorporated in to the double polymeric system. The objective of this study was to investigate the feasibility of PLDEX polymeric microspheres as an adjuvant for hepatitis B vaccine (HBsAg). The present study demonstrates the immunogenicity profile of HBsAg encapsulated in PLDEX and compared their efficacy with alum adsorbed HBsAg. The single intramuscular injection of HBsAg loaded PLDEX microspheres in Wistar rats resulted satisfactory antibody titers. Based on in vivo findings PLDEX microspheres were able induce satisfactory immune response.