R. T. Altaee, M. G. Aldabbagh, O. Y. Al-Abbasy

Department of Chemistry, College of Education for Pure Sciences, University of Mosul, Iraq;
*e-mail: chem.omar1978@uomosul.edu.iq

Received: 09 January 2026; Revised: 29 January 2026;
Accepted: 03 April 2026; Available on-line: April 2026

Excessive accumulation of adipose tissue is a hallmark of obesity as a critical factor in the development of numerous chronic medical problems. Pancreatic lipase (PLase), which controls the absorption of fats in the intestine, has gained significance as a target in anti-obesity therapy. This study aimed to evaluate the potential effects of Aspirin as a PLase inhibitor and a weight-loss agent compared to the commonly used anti-obesity drug Xenical. Pancreatic lipase was purified 28.5-fold from the plasma of obese male volunteers using ion-exchange chromatography. Enzyme activity was evaluated using p-nitrophenyl butyrate as a substrate. The kinetic analysis of Aspirin effect on purified enzyme activity revealed a competitive inhibition mechanism with K_i of 24.3 mM. In vivo studies were performed using 20 male Wistar rats randomly divided into four equal groups provided with: 1 – control conditions; 2 – high-fat diet (HFD) for 12 weeks; 3 – HFD and Xenical orally (10 mg/kg BW daily); 4 – HFD and Aspirin orally (14.4 mg/kg BW daily). In an HFD group, increased animals body weight and elevated PLase activity in plasma compared to the control were demonstrated. Treatment with both Aspirin and Xenical resulted in a significant decrease in body weight and PLase activity compared with untreated HFD rats. Molecular docking of Human Pancreatic lipase-related protein 1 (PDB ID: 2PPL) binding with Aspirin and Xenical showed the values of binding energy (ΔG) 5.4 and -4.4 kcal/mol, respectively, indicating a stronger protein interaction with Aspirin compared to Xenical. This combined study reinforces the conclusion that Aspirin has the potential to be a novel anti-obesity agent.