Antiangiogenic Effect of Pluchea lanceolata in Adjuvant-Induced Rheumatoid Arthritis in Wistar Rats by Downregulating VEGF Signaling Pathway and Proinflammatory Cytokines

The current work aimed to investigate the therapeutic potential of Pluchea lanceolata (Rasna) in the management of rheumatoid arthritis (RA) using in silico, in vitro, and in vivo studies. After administering Rasna (aqueous and ethanolic extracts), physical parameters such as paw volume and arthritic score were found suppressed in rats (in Freund’s complete adjuvant-induced model). Also, radiography and histopathological findings revealed that joint deformities, pannus formation, and tissue swelling of the ankle joint improved when compared with standard and arthritis-induced after 4 weeks. Simultaneously, ELISA results revealed that the serum levels of IL-1β, IL-6, TNF-α, C-reactive protein (CRP), and COL2A1 were lowered when compared with the standard group. An in silico study revealed that quercetin, isorhamnetin, and linalool were the potential active phytoconstituents and showed promising binding affinity toward targets such as KDR (VEGFR2), matrix metalloproteinase (MMPs), ALOX5, IL-1β, IL-6, TNF-α, CRP, and COL2A1. The biological mechanism of Rasna includes several molecular and cellular functions involving the downregulation of angiogenesis through the vascular endothelial growth factor signaling pathway, the MAPK signaling pathway, PI3K-Akt signaling pathway, and the reduction of cytokines and anti-collagen II antibodies. Rasna inhibits the activation of the abovementioned pathways and mRNA expression of IL-1β, IL-6, and TNF-α in RA. The study suggested the potential use of Rasna in managing arthritis treatment over the conventional therapy in immunocompromised patients.