Insights into the Anorexic Potential of Khat: An Integrated in vivo, ex vivo, and in silico Investigation

Abstract Chewing khat (Catha edulis) releases cathine and cathinone, which may reduce appetite through an unknown mechanism. This study investigated the peripheral and central effects of fresh leaves and buds of C. edulis water extract (CEWE) on appetite and body weight, using in vivo, ex vivo, and in silico models. Rats of both sexes were used for three different experiments. Serotonin receptors were studied using isolated rat fundus samples and molecular docking. Significant differences in body weight were observed in the CEWE-treated groups compared with the controls over eight weeks. However, plasma leptin and ghrelin levels did not change significantly. The expression of the ghrelin and leptin genes was also unaffected, but the expression of the 5-HT gene decreased with CEWE treatment. CEWE antagonizes 5-HT receptors in isolated rat fundus samples. In silico docking indicated that the khat ligands inhibited 5-HT2C receptors. Cathine and cathinone levels in rat plasma were measured. These findings suggest that the appetite-suppressing role of khat can be attributed to its antagonistic effect on 5-HT receptors. Further research is needed to fully understand the mechanism of action of the khat extract. These findings provide a basis for future studies to validate and expand on these discoveries.