The immunomodulatory activity of Orthosiphon aristatus against atopic dermatitis: Evidence-based on network pharmacology and molecular simulations

Abstract

Objectives: To explore the potential activity of Orthosiphon aristatus (OA) against atopic dermatitis (AD). Methods: Phytocompounds from OA were identified through chromatography analysis, then continued to target identification and functional annotation to explore the potential target of OA. Then, network pharmacology from annotated proteins determined protein targets for OA phytocompounds. Protein with highest rank according to the betweenness and closeness algorithm then continued to molecular docking and validated through molecular dynamics analysis. Results: Chromatography data analysis revealed thirtysix compounds, predominantly classified as carboxylic acid, fatty acyls, and polyphenols. Upon identifying these compounds, network biology-based target identification revealed their potential bioactivity in modulating inflammation in AD. Tumour Necrosis Factor-alpha (TNF-a) and Prostaglandin G/H synthase 2 (PTGS2) emerged as the most probable targets based on hub centrality in the proteineprotein interaction network. Later, molecular docking analyses highlighted sixteen compounds with good inhibitory activity against these two proteins. Notably, molecular dynamics simulation revealed that three compounds out of the previous sixteen potential compounds were more likely to act as the TNFa and PTGS2 inhibitor as well as their native inhibitor. Those compounds are (1R,9R)-5-Cyclohexyl-11- (propylsulfonyl)- 7,11- diazatricyclo[7.3.1.02,7]trideca- 2,4- dien-6-one, also known as ZINC8297940, as the best TNF-a inhibitor along with dl-Leucineamide and Benazol P as the potential inhibitor of PTGS2. Conclusions: These findings suggest that OA may exert therapeutic effects against AD by controlling inflammation through TNF-a and PTGS2 signalling pathways.