Inhibition of human pancreatic lipase by aspirin: experimental and in silico study

13.04.2026   Uncategorized

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 Ki 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.

Keywords: , , , , , , ,

References:

  1. Mhatre SV, Bhagit AA, Yadav RP. Pancreatic lipase inhibitor from food plant: Potential molecule for development of safe anti-obesity drug. MGM J Med Sci. 2016;3(1):34-41. CrossRef
  2. Liu TT, Liu XT, Chen QX, Shi Y. Lipase Inhibitors for Obesity: A Review. Biomed Pharmacother. 2020;128:110314. PubMed, CrossRef
  3. Bjerregaard LG, Jensen BW, Ängquist L, Osler M, Sørensen TIA, Baker JL. Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes. N Engl J Med. 2018;378(14):1302-1312. PubMed, CrossRef
  4. Doll S, Paccaud F, Bovet P, Burnier M, Wietlisbach V. Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries. Int J Obes Relat Metab Disord. 2002;26(1):48-57. PubMed, CrossRef
  5. Teixeira LG, Leonel AJ, Aguilar EC, Batista NV, Alves AC, Coimbra CC, Ferreira AV, de Faria AM, Cara DC, Alvarez Leite JI. The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation. Lipids Health Dis. 2011;10:204. PubMed, PubMedCentral, CrossRef
  6. Ernst ND. NIH Consensus Development Conference on lowering blood cholesterol to prevent heart disease: implications for dietitians. J Am Diet Assoc. 1985;85(5):586-588. PubMed, CrossRef
  7. Alrushdi FMM, Al-Abaasy OYM, Al-Saffar RN, Abbood HY, Al-Hamairy AK, Saleh MY, Abdelzaher H, Abdelzaher MA, Kenawy MA. In vitro: inhibition of partially purified pancreatic ovine lipase by willow bark extracts. J Biosci Appl Res. 2025;11(1):168-179. CrossRef
  8. Alabbas KS, Salih OA, and Al-Abbasy OY. Isolation, Purification, and Characterization of Pecan Nut Lipase and Studying its Affinity towards Pomegranate Extracts and 1, 4-Diacetoxybenzene. Iraqi J Sci. 2022;63(3):908-922. CrossRef
  9. Huang X, Zhu J, Wang L, Jing H, Ma C, Kou X, Wang H. Inhibitory mechanisms and interaction of tangeretin, 5-demethyltangeretin, nobiletin, and 5-demethylnobiletin from citrus peels on pancreatic lipase: Kinetics, spectroscopies, and molecular dynamics simulation. Int J Biol Macromol. 2020;164:1927-1938. PubMed, CrossRef
  10. Javed S, Azeem F, Hussain S, Rasul I, Siddique MH, Riaz M, Afzal M, Kouser A, Nadeem H. Bacterial lipases: A review on purification and characterization. Prog Biophys Mol Biol. 2018;132:23-34. PubMed, CrossRef
  11. Patel N, Rai D, Shivam, Shahane S, Mishra U. Lipases: Sources, Production, Purification, and Applications. Recent Pat Biotechnol. 2019;13(1):45-56. PubMed, CrossRef
  12. Tuzimski T, Petruczynik A. New trends in the practical use of isoquinoline alkaloids as potential drugs applicated in infectious and non-infectious diseases. Biomed Pharmacother. 2023;168:115704. PubMed, CrossRef
  13. Rani N, Vasudeva N, Sharma SK. Quality assessment and anti-obesity activity of Stellaria media (Linn.) Vill. BMC Complement Altern Med. 2012;12:145. PubMed, PubMedCentral, CrossRef
  14. Chanoine JP, Hampl S, Jensen C, Boldrin M, Hauptman J. Effect of orlistat on weight and body composition in obese adolescents: a randomized controlled trial. JAMA. 2005;293(23):2873-2883. PubMed, CrossRef
  15. Chauhan D, George G, Sridhar SNC, Bhatia R, Paul AT, Monga V. Design, synthesis, biological evaluation, and molecular modeling studies of rhodanine derivatives as pancreatic lipase inhibitors. Arch Pharm (Weinheim). 2019;352(10):e1900029. PubMed, CrossRef
  16. Thi Vo CV, Thanh Nguyen T, Ngoc Dang T, Quoc Dao M, Thao Vo V, Thi Tran O, Thanh Vu L, Tran TD. Design, synthesis, biological evaluation and molecular docking of alkoxyaurones as potent pancreatic lipase inhibitors. Bioorg Med Chem Lett. 2024;98:129574. PubMed, CrossRef
  17. Wichapong K, Rohe A, Platzer C, Slynko I, Erdmann F, Schmidt M, Sippl W. Application of docking and QM/MM-GBSA rescoring to screen for novel Myt1 kinase inhibitors. J Chem Inf Model. 2014;54(3):881-893. PubMed, CrossRef
  18. Robyt JF, White BJ. Biochemical techniques: theory and practice. 1987. 450 p.
  19. Lee D, Koh Y, Kim K, Kim B, Choi H, Kim D, Suhartono MT, Pyun Y. Isolation and characterization of a thermophilic lipase from bacillus thermoleovorans ID-1. FEMS Microbiol Lett. 1999;179(2):393-400. PubMed, CrossRef
  20. Al-Abbasy OY, Ali WI, Younus SA. Study on inhibitory effect of Rosmarinus officinalis L extracts and Quercitine on partially purified cow’s brain polyamine oxidase. Biochem Cell Arch. 2020;20(2):5617-5625.
  21. Younus SA, Mahdi NM, Al-Abbasy OY, Ahmad OAS. Antioxidative effect of Maillard reaction products of spermine-sugar system on partially purified plum polyphenol oxidase. J Food Sci Technol. 2025;22(160):227-241. CrossRef
  22. Smine S Obésité induite par un régime riche en lipides (HFD) et effet protecteur d’un extrait polyphénolique de raisin (GSSE): approche protéomique. Normandie Université; Université de Tunis El Manar. 2017.
  23. Mahdi NM, Younus SA, Al-Burgus AF, Al-Abbasy OY. In vivo, in vitro, and molecular docking study of rat pancreatic lipase inhibition using isopropyl salicylate. Ukr Biochem J. 2025;97(4):84-93. CrossRef
  24. Zaitone SA, Essawy S. Addition of a low dose of rimonabant to orlistat therapy decreases weight gain and reduces adiposity in dietary obese rats. Clin Exp Pharmacol Physiol. 2012;39(6):551-559. PubMed, CrossRef
  25. Novelli EL, Diniz YS, Galhardi CM, Ebaid GM, Rodrigues HG, Mani F, Fernandes AA, Cicogna AC, Novelli Filho JL. Anthropometrical parameters and markers of obesity in rats. Lab Anim. 2007;41(1):111-119. PubMed, CrossRef
  26. Wahabi S, Rtibi K, Atouani A, Sebai H. Anti-Obesity Actions of Two Separated Aqueous Extracts From Arbutus (Arbutus unedo) and Hawthorn (Crataegus monogyna) Fruits Against High-Fat Diet in Rats via Potent Antioxidant Target. Dose Response. 2023;21(2):15593258231179904. PubMed, PubMedCentral, CrossRef
  27. Al-Burgus AF, Thanoon-Ali O, and O.Y. Al-Abbasy OY. Design, synthesis and molecular docking of new spiro heterocyclic coumarin as antibacterial agents. Rev Roum Chim. 2024;69(7-8):399-404. CrossRef
  28. Hevener KE, Zhao W, Ball DM, Babaoglu K, Qi J, White SW, Lee RE. Validation of molecular docking programs for virtual screening against dihydropteroate synthase. J Chem Inf Model. 2009;49(2):444-460. PubMed, PubMedCentral, CrossRef
  29. Phan CT, Tso P. Intestinal lipid absorption and transport. Front Biosci. 2001;6:D299-D319. PubMed, , CrossRef
  30. Woolley P, Petersen SB. Sequence analysis of lipases, esterases and related proteins. In: Lipases: their structure, biochemistry and application. 1994: 27-28.
  31. Iizuka K, Higurashi H, Fujimoto J, Hayashi Y, Yamamoto K, Hiura H. Purification of human pancreatic lipase and the influence of bicarbonate on lipase activity. Ann Clin Biochem. 1991;28(Pt 4):373-378. PubMed, CrossRef
  32. Kimura H, Futami Y, Tarui S, Shinomiya T. Activation of human pancreatic lipase activity by calcium and bile salts. J Biochem. 1982;92(1):243-251. PubMed, CrossRef
  33. Di Bella S, Luzzati R, Principe L, Zerbato V, Meroni E, Giuffrè M, Crocè LS, Merlo M, Perotto M, Dolso E, Maurel C, Lovecchio A, Dal Bo E, Lagatolla C, Marini B, Ippodrino R, Sanson G. Aspirin and Infection: A Narrative Review. Biomedicines. 2022;10(2):263. PubMed, PubMedCentral, CrossRef
  34. Ninomiya K, Matsuda H, Shimoda H, Nishida N, Kasajima N, Yoshino T, Morikawa T, Yoshikawa M. Carnosic acid, a new class of lipid absorption inhibitor from sage. Bioorg Med Chem Lett. 2004;14(8):1943-1946. PubMed, CrossRef
  35. Zhao HL, Kim YS. Determination of the kinetic properties of platycodin D for the inhibition of pancreatic lipase using a 1,2-diglyceride-based colorimetric assay. Arch Pharm Res. 2004;27(10):1048-1052. PubMed, CrossRef
  36. Won SR, Kim SK, Kim YM, Lee PH, Ryu JH, Kim JW, Rhee HI. Licochalcone A: A lipase inhibitor from the roots of Glycyrrhiza uralensis. Food Res Int. 2007;40(8):1046-1050. CrossRef
  37. Rajan L, Das N, Chakkyarath V, Natarajan J, Palaniswamy D, Shaw S, Mishra SK. Pancreatic lipase related protein 1 as a potential target in triglyceride breakdown: A molecular docking studies with in vitro appraisal. Results Chem. 2023;5:100960. CrossRef
  38. Tran TH, Mai TT, Ho TT, Le TN, Cao TC, Thai KM, Tran TS. Inhibition of Pancreatic Lipase by Flavonoid Derivatives: In Vitro and In Silico Investigations. Adv Pharmacol Pharm Sci. 2024;2024:6655996. PubMed, PubMedCentral, CrossRef
  39. Wu X, He W, Zhang H, Li Y, Liu Z, He Z. Acteoside: a lipase inhibitor from the Chinese tea Ligustrum purpurascens kudingcha. Food Chem. 2014;142:306-310. PubMed, CrossRef
  40. Egloff MP, Marguet F, Buono G, Verger R, Cambillau C, van Tilbeurgh H. The 2.46 A resolution structure of the pancreatic lipase-colipase complex inhibited by a C11 alkyl phosphonate. Biochemistry. 1995;34(9):2751-2762. PubMed, CrossRef
  41. Hadváry P, Sidler W, Meister W, Vetter W, Wolfer H. The lipase inhibitor tetrahydrolipstatin binds covalently to the putative active site serine of pancreatic lipase. J Biol Chem. 1991;266(4):2021-2027. PubMed, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.