Inhibition of pancreatic elastase in silico and in vitro by Rubus rosifolius leaves extract and its constituents

Yesi Desmiaty; Esti Mulatsari; Fadlina Chany Saputri; Muhammad Hanafi; Rini Prastiwi; Berna Elya

doi:10.4103/jpbs.JPBS_271_19

Inhibition of pancreatic elastase in silico and in vitro by Rubus rosifolius leaves extract and its constituents

J Pharm Bioallied Sci. 2020 Jul-Sep;12(3):317-323. doi: 10.4103/jpbs.JPBS_271_19. Epub 2020 Jul 18.

Authors

Yesi Desmiaty^{1

2}, Esti Mulatsari¹, Fadlina Chany Saputri², Muhammad Hanafi^{1

3}, Rini Prastiwi⁴, Berna Elya²

Affiliations

¹ Department of Phytochemistry, Faculty of Pharmacy, Pancasila University, Jakarta, Indonesia.
² Department of Phytochemistry, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
³ Research Centre for Chemistry Indonesian Institute of Sciences, Jakarta, Indonesia.
⁴ Department of Pharmacognosy, Faculty of Pharmacy, Universitas Muhammadiyah Prof. Dr. Hamka, Jakarta, Indonesia.

Abstract

Objective: Elastases are protease enzymes, which mainly hydrolyze proteins of the connective tissue, so they have a significant impact on human disease. Rubus rosifolius is one of the Rubus species found in Indonesian mountains, and it has potential as an elastase inhibitor. The objective of this research was to examine the in vitro elastase inhibitor activity of R. rosifolius leaves and to dock different ligands of its constituents against target protein of Porcine Pancreatic Elastase (PPE) receptor.

Method: Dried leaves powder of R. rosifolius was extracted using Soxhlet apparatus with n-hexane, ethyl acetate, and methanol. The extract was evaporated, and in vitro elastase inhibitor activity was determined using PPE with the quercetin used as control positive. Selected nine constituents of R. rosifolius were evaluated on the docking behavior of elastase receptor using Protein-Ligand ANT System (PLANTS) computational software with PPE enzyme with Protein Data Bank (PDB) file 1BRU.

Result: The methanol extract showed significantly inhibited elastase with IC50 186.13 μg/mL, but ethyl acetate extract showed weak activity, and n-hexane extract did not show any activity. Docking studies and binding free energy calculations and hydrogen bonding with some amino acids revealed that ellagic acid showed the least binding energy for the target enzyme.

Conclusion: This research has opened new insights into understanding that constituents of R. rosifolius methanol extract are potential inhibitors against elastase, and suggested the active compound is ellagic acid.

Keywords: Docking studies; Rubus rosifolius; elastase inhibitor; ellagic acid.