Multi-Target Pharmacological Evaluation of Embelin and Piperine against Rheumatoid Arthritis: A Network Pharmacology and Molecular Docking Study

Abstract

Rheumatoid arthritis is a chronic autoimmune inflammatory illness that causes synovial inflammation, cartilage degradation, joint deterioration, and increasing disability. Conventional medicinal techniques are frequently linked with side effects and poor long-term success, prompting the search for safer multitarget phytotherapeutics. The present study used an integrated network pharmacology and molecular docking technique to examine Embelin and Piperine's antiarthritic potential. SwissTargetPrediction and PubChem were used to identify potential Embelin and Piperine targets, while the GeneCards database was used to find rheumatoid arthritis-associated targets. To discover critical hub genes, common targets were studied using protein-protein interaction (PPI) networks. GO and KEGG pathway enrichment analysis revealed a considerable involvement of inflammatory and immune-regulatory pathways, notably the PI3K-Akt signaling pathway. The Key hub genes discovered were HSP90AA1, SRC, PIK3CA, JAK2, PTK2, and MET. Piperine binds strongly to HSP90AA1 (-7.2 kcal/mol) and JAK2 (-7.5 kcal/mol), similar to the standard treatment Tofacitinib (-7.5 kcal/mol), according to a molecular docking investigation. Embelin had a positive affinity with HSP90AA1 (-6.1 kcal/mol) and JAK2 (-5.8 kcal/mol). These data indicate that Embelin and Piperine may have antiarthritic properties through multitarget regulation of inflammatory and immunological pathways.