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. 2024 Mar 21:15:1358037.
doi: 10.3389/fphar.2024.1358037. eCollection 2024.

In silico identification of compounds from Piper sarmentosum Roxb leaf fractionated extract inhibit interleukin-6 to prevent rheumatoid arthritis

Tran Nhat Phong Dao  1   2 , Sunday Amos Onikanni  3   4 , Adewale Oluwaseun Fadaka  5 , Ashwil Klein  5 , Van De Tran  6 , Minh Hoang Le  2 , Chih-Hao Wang  3   7 , Hen-Hong Chang  1   8   9
Affiliations

In silico identification of compounds from Piper sarmentosum Roxb leaf fractionated extract inhibit interleukin-6 to prevent rheumatoid arthritis

Tran Nhat Phong Dao et al. Front Pharmacol. .

Abstract

Objective: Medicinal herbs with a phytonutrient background has been applied globally as major alternatives to ameliorate the continuous increase in rheumatoid arthritis cases worldwide. We herein aimed to critically examine the bioactive components of the medicinal herb Piper sarmentosum Roxb leaf fractionated extract for its potential to inhibit the influx of interleukin-6 (IL-6) in rheumatoid arthritis. Methods: The Schrödinger platform was employed as the main computational acumen for the screening of bioactive compounds identified and reference compounds subjected to molecular simulation (MDS) for analyzing the stability of docked complexes to assess fluctuations and conformational changes during protein-ligand interactions. Results: The values of the simulatory properties and principal component analysis (PCA) revealed the good stability of these phytochemicals in the active pocket of interleukin-6 (IL-6). Discussion: Our findings reveal new strategies in which these phytochemicals are potential inhibitory agents that can be modified and further evaluated to develop more effective agents for the management of rheumatoid arthritis, thereby providing a better understanding and useful model for the reproduction and/or discovery of new drugs for the management of rheumatoid arthritis and its complications.

Keywords: conformational; interleukin-6; phytonutrient; rheumatoid arthritis; simulation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The ADEMET predictive study of (A) WSP water soluble properties, (B) pharmacokinetics, lipophilicity, (C) drug likeness and medicinal chemistry of the top-scoring compounds from PS leaf fractionated extract.
FIGURE 2
FIGURE 2
Comprehensive 2D and 3D molecular interaction data for 5280441 with the receptor (interleukin-6 (IL-6)) obtained from docking analysis.
FIGURE 3
FIGURE 3
Comprehensive 2D and 3D molecular interaction data for 5281672 with the receptor (interleukin-6 (IL-6)) obtained by docking analysis.
FIGURE 4
FIGURE 4
Comprehensive 2D and 3D molecular interaction packages of 5280343 with the receptor (interleukin-6 (IL-6)) from docking analysis.
FIGURE 5
FIGURE 5
Comprehensive 2D and 3D molecular interaction packages of 5280443 with the receptor (Interleukin-6 (IL-6)) from docking analysis.
FIGURE 6
FIGURE 6
Comprehensive 2D and 3D molecular interaction packages of 439246 with the receptor (interleukin-6 (IL-6)) from docking analysis.
FIGURE 7
FIGURE 7
Comprehensive 2D and 3D molecular interaction packages of 5280863 with the receptor (interleukin-6 (IL-6)) from the docking analysis.
FIGURE 8
FIGURE 8
Comprehensive 2D and 3D molecular interaction packages of 5281601 with the receptor (interleukin-6 (IL-6)) from docking analysis.
FIGURE 9
FIGURE 9
Comprehensive 2D and 3D molecular interaction packages of standard with the receptor (Interleukin-6 (IL-6)) from the docking analysis.
FIGURE 10
FIGURE 10
Plot of free binding energy against docking score from in silico analysis of the ligands identified from the fractionated Piper sarmentosum Roxb leaf extract.
FIGURE 11
FIGURE 11
MD simulation of 1P9M complexed with 5280343 (quercetin), 5280443 (apigenin), 5280863 (kaempferol) and 5281601 (5-hydroxy-7,4-dimethoxyflavone). (A) L_RMSD and (B) P_RMSF graphical illustration plots. All the simulations were carried out using the Schrödinger suite version maestro v21.3.
FIGURE 12
FIGURE 12
MD simulation of 1P9M complexed with 5280343 (quercetin), 5280443 (apigenin), 5280863 (kaempferol) and 5281601 (5-hydroxy-7,4-dimethoxyflavone). (A) MolSA representation and (B) SASA diagram. All the simulations were carried out using the Schrödinger suite version maestro v21.3.
FIGURE 13
FIGURE 13
MD simulation of 1P9M complexed with 5280343 (quercetin), 5280443 (apigenin), 5280863 (kaempferol) and 5281601 (5-hydroxy-7,4-dimethoxyflavone). (A) rGyr representation and (B) PSA diagram. All the simulations were carried out using the Schrödinger suite version maestro v21.3.
FIGURE 14
FIGURE 14
Principal component analysis of the native protein and ligands: (B) 5280443 (apigenin), (C) 5280863 (kaempferol), (D) 5280343 (quercetin), and (E) 5281601 (5-hydroxy-7,4-dimethoxyflavone).
FIGURE 15
FIGURE 15
Eigenvalues against principal component analysis of the native protein and ligands: (A) 5280443 (apigenin), (B) 5280863 (kaempferol), (C) 5280343 (quercetin), and (D) 5281601 (5-hydroxy-7,4-dimethoxyflavone).
FIGURE 16
FIGURE 16
Schematic illustration of (A) Boltzmann and (B) Gaussian accelerated molecular dynamics of the ligands: ligands 5280343 (quercetin), 5280443 (apigenin), 5280863 (kaempferol) and 5281601 (5-hydroxy-7,4-dimethoxyflavone).
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