In Silico Analysis of PTP1B Inhibitors and TLC-MS Bioautography-Based Identification of Free Radical Scavenging and α-Amylase Inhibitory Compounds from Heartwood Extract of Pterocarpus marsupium

Mohammad Irfan Dar; Mohammad Irfan Qureshi; Sultan Zahiruddin; Sageer Abass; Bisma Jan; Armiya Sultan; Sayeed Ahmad

doi:10.1021/acsomega.2c04283

In Silico Analysis of PTP1B Inhibitors and TLC-MS Bioautography-Based Identification of Free Radical Scavenging and α-Amylase Inhibitory Compounds from Heartwood Extract of Pterocarpus marsupium

ACS Omega. 2022 Dec 9;7(50):46156-46173. doi: 10.1021/acsomega.2c04283. eCollection 2022 Dec 20.

Authors

Mohammad Irfan Dar¹, Mohammad Irfan Qureshi¹, Sultan Zahiruddin², Sageer Abass¹, Bisma Jan^{2

3}, Armiya Sultan¹, Sayeed Ahmad²

Affiliations

¹ Department of Biotechnology, Jamia Millia Islamia, New Delhi110025, India.
² Centre of Excellence in Unani Medicine (Pharmacognosy & Pharmacology) and Bioactive Natural Product Laboratory, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi110062, India.
³ Department of Food Technology School of Interdisciplinary Science & Technology, Jamia Hamdard, New Delhi110062, India.

Abstract

Type 2 diabetes mellitus leads to metabolic impairment caused by insulin resistance and hyperglycemia, giving rise to chronic diabetic complications and poor disease prognosis. The heartwood of Pterocarpus marsupium has been used in Ayurveda for a long time, and we sought to find the actual mechanism(s) driving its antidiabetic potential. Methanol was used to prepare the extract using a Soxhlet extraction, and the identification of metabolites was performed by thin-layer chromatography (TLC) and ultraperformance-liquid chromatography and mass spectroscopy (UP-LCMS). The antioxidant potential of methanolic heartwood extract of Pterocarpus marsupium MHPM was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and a reducing power assay. The α-amylase and α-glucosidase enzyme inhibitory potential of MHPM were investigated for their antidiabetic activity against acarbose. TLC-MS-bioautography was performed to identify the compounds responsible for possible antioxidant and antidiabetic activities. Moreover, targeting protein tyrosine phosphatase 1B (PTP1B), a key regulator of insulin resistance, by identified metabolites from MHPM through molecular docking and all-atom molecular dynamics (MD) simulations was also undertaken, suggesting its potential as an antidiabetic herb. The IC₅₀ of free-radical scavenging activity of MHPM against DPPH was 156.342 ± 10.70 μg/mL. Further, the IC₅₀ values of MHPM in α-amylase and α-glucosidase enzymatic inhibitions were 158.663 ± 10.986 μg/mL and 180.21 ± 11.35 μg/mL, respectively. TLC-MS-bioautography identified four free radical scavenging metabolites, and vanillic acid identified by MS analysis showed both free radical scavenging activity and α-amylase inhibitory activity. Among the identified metabolites from MHPM, epicatechin showed significant PTP1B docking interactions, and its MD simulations revealed that PTP1B forms a stable protein-ligand complex with epicatechin throughout the progression, which indicates that epicatechin may be used as a promising scaffold in the development of the antidiabetic drug after isolation from Pterocarpus marsupium. Overall, these findings imply that Pterocarpus marsupium is a source of valuable metabolites that are accountable for its antioxidant and antidiabetic properties.