Structure-based screening of inhibitor platelet-derived growth factor from ethanol extract of Uncaria gambir (Hunter) Roxb. as an antifibrotic in keloid fibroblast cells

Abstract

This study aimed to determine the potency of the compounds in gambir [Uncaria gambir (Hunter) Roxb.] to inhibit the proliferation of keloid fibroblasts using an in silico study with molecular docking and an in vitro assay. In this study, the interaction between compounds found in the gambir plant and platelet-derived growth factor subunit A (PDGF-α) as the target protein and the percentage inhibition were analyzed to determine its potential as a candidate for herbalbased keloid therapy. The compounds found in the plant gambir [(+)-catechin, gambirin A1, gambirin A2, gambirin B1, gambirin B2, gambirin C, procyanidin B1, procyanidin B2, epigallocatechin gallate, and (+)-epicatechin] were docked to the target protein PDGF-α (PBD ID: 3MJK). An MTT assay was conducted to determine the cytotoxicity of each compound. The three compounds gambirin A1, procyanidin B2, and neooxygambirtannine had the best affinity values 10.218, and 9.129, respectively. The IC 50 of the ethanolic extract of gambir was 22.40 ± 0.071 ug/ml against keloid fibroblast cells. The potential bioactive compounds as PDGF inhibitors have been identified, namely, gambirin A1, procyanidin B2, and neooxygambirtannine. These compounds can be isolated for further research. IC 50 can be used to understand the molecular mechanism of the inhibition of the gambir extract against keloid fibroblast cells.

Profibrotic Inflammatory Cytokines and Growth Factors Are Predicted as the Key Targets of Uncaria gambir (Hunter) Roxb. in Keloids: An Epistatic and Molecular Simulation Approach

“…A total 74 bioactive compounds of Uncaria gambir (Hunter) Roxb. were identified from the literature study [ 9 , 17 , 24 ], with 5048 protein-specific targets based on SWISS target prediction. A total of 277 targets from 29 bioactive compounds were predicted to be targeted to keloid-related target proteins.…”

“…Keloid is defined as tissue fibrosis due to its effusive accumulation of ECM, particularly collagen [ 2 ]. Jusman et al [ 17 ] have shown that some gambir bioactive compounds have potency to inhibit platelet-derived growth factor subunit A (PDGFA) as a target protein to reduce fibroblast proliferation through in silico study. Therefore, gambir is assumed to be a promising herb-based antifibrotic agent to deal with keloid disease.…”