Simulation-Based Research on Phytoconstituents of Embelia ribes Targeting Proteins with Pathophysiological Implications in Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a heterogeneous inflammatory disease with an autoimmune origin and an incompletely elucidated pathophysiological mechanism. RA pharmacotherapy is based on chemically or biologically active substances that provide clinical alleviation and remission, but the disease is still incurable. As a result, there remains a need for significant therapeutic development, and adjuvant therapies may play an essential role in the search for novel RA treatment strategies. The aim of the present study was to investigate potential phytocompounds and phytocompound derivates as RA treatment agents, using in silico methodologies. In this regard, five phytoconstituents identified in different structures of Embelia ribes were evaluated by in silico methods for their potential action on target proteins of therapeutic interest in RA. The methodology involved identifying the phytocompound with the highest binding toward the target protein via molecular docking using AutoDock Vina 1.5.7, followed by a ligand-based virtual screening based on the structure of the most promising phytocompound using SwissSimilarity. This process led to the identification of ligands that are not currently utilized in medical practice, but that might have the potential to be used in the management of RA after further extensive experimental endorsements. ZINC000004024651 showed the highest binding affinity for the Bruton’s tyrosine kinase protein, followed by ZINC000000434197 for p38 mitogen-activated protein kinases, ZINC000087606977 for interleukin-1 receptor-associated kinase 4, and ZINC000014728393 for matrix metallopeptidase 9, the latter two showing higher affinity than the co-crystallized compound. The relatively high affinities to target proteins and the pharmacokinetic data obtained by in silico studies using SwisADME suggest a first step for the inclusion of promising new compounds in various more advanced studies, leading to the evaluation of efficacy and safety profiles.

Based on Network Pharmacology and Molecular Docking, the Active Components, Targets, and Mechanisms of Flemingia philippinensis in Improving Inflammation Were Excavated

“…Numerous plants are rich in natural anti-inflammatory constituents, such as polyphenols, flavonoids, and terpenes. These components significantly alleviate inflammatory responses by inhibiting the release of inflammatory mediators, reducing oxidative stress, and modulating immune responses [ 36 , 37 , 38 ]. Although the anti-inflammatory effects of Flemingia philippinensis have been reported, the underlying mechanisms remain unclear.…”

New insights into the influence of encapsulation materials on the feasibility of ultrasonic-assisted encapsulation of Mosla chinensis essential oil

“…The main component (carvacrol) from Mosla chinensis EO was chosen to search for the interaction between the EO and the CDs. At first, the potential complex formation between carvacrol and CDs was calculated by AutoDock Vina (version 1.5.7) [42] . The crystal structures of α-CD, β-CD, and γ-CD were collected from the Cambridge Crystallographic Data Centre (CCDC) named 1106001, 1235577, and 1126610, respectively [43] .…”