Downmodulation of lysophosphatidic acid by Berberine loaded folate-conjugated glycol chitosan nanoparticles (BFGCN) to mitigate Rheumatoid arthritis (RA) & Cardio-vascular disease(CVD): Current knowledge and future perspectives

The perils of cardiovascular diseases (CVD) are enhanced by systemic chronic inflammation in autoimmune disorders like Rheumatoid arthritis (RA), in which the patients generally exhibit a high inflammatory burden, dyslipidemia causing 50-60% of RA patients susceptible to CVD dependent mortality. Lysophosphatidic acid (LPA) is a polar, pleiotropic lipid molecule that is water soluble and present in the synovial fluid that can be exploited as an effective biomarker for lipid-signalling. Current research on alternative medicine has recognized various new molecular targets of Berberine (BBR) and established novel signals in support of the efficacy and therapeutic potential of BBR to fight CVD. Therefore, BBR, an alkaloid with poor aqueous solubility could be foreseen as a therapeutic strategy for the reduction of inflammation induced lipidemia by targeting the macrophages and modulating their functions. Hence, a novel BBR loaded folate-conjugated glycol chitosan nanoparticles (BFGCN) could be hypothesized as a three-pronged approach to target activated macrophages, fibroblasts of synovial fluid for downmodulation of LPA. The greatest challenge is the heterogeneity, complexity and interdependence of RA and CVD. Investigation of prognostic and predictive biomarkers is urgently required. Therefore, an improved understanding of the pathogenesis of RA would facilitate identifying an improved targeted treatment and management of RA patients.