Transcriptomic profiling revealed the role of apigenin-4′-O-α-L-rhamnoside in inhibiting the activation of rheumatoid arthritis fibroblast-like synoviocytes via MAPK signaling pathway

Abstract

BackgroundActivated fibroblast-like synoviocyte (FLS) played a significant role in the pathogenesis and progression of rheumatoid arthritis (RA). Apigenin-4′-O-α-L-rhamnoside showed remarkable effects against RA, however, no relevant studies on pharmacology of apigenin-4′-O-α-L-rhamnoside yet, the effects and underlying molecular mechanism of apigenin-4′-O-α-L-rhamnoside on RA are still unclear. PurposeThis study aimed to investigate the therapeutic effects and mechanisms of apigenin-4′-O-α-L-rhamnoside on RA-FLS cells by transcriptomic analysis. MethodsIn vitro, RA-FLS cell viability and migration were measured by CCK-8 and scratch assays, respectively. The effects of apigenin-4′-O-α-L-rhamnoside on inflammatory levels of MMP-1, MMP-3, RANKL and TNF-α in RA-FLS cells were detected using ELISA kits. High-throughput transcriptome analysis was performed to screen the key genes and related pathways of apigenin-4′-O-α-L-rhamnoside inhibit RA-FLSs, and the result of which were validated by RT-qPCR and western blot. Furthermore, in vivo, we also evaluated the effects of apigenin-4′-O-α-L-rhamnoside in rat with CIA. ResultsApigenin-4′-O-α-L-rhamnoside significantly suppressed RA-FLS migration, exerted remarkable inhibiting effects on the expression levels on MMP-1, MMP3, RANKL and TNF-α in RA-FLS cells. It seemed that MAPK signaling pathway might be closely related to the pathogenesis of RA by down-regulated relevant core targets (MAPK1, HRAS, ATF-2, p38 and JNK). Moreover, apigenin-4′-O-α-L-rhamnoside attenuated the severity of arthritis in CIA rat. ConclusionApigenin-4′-O-α-L-rhamnoside inhibited pro-inflammatory cytokine, chemokine and MMPs factors production of RA-FLS by targeting the MAPK signaling pathway, which provided a scientific basis for potential application in the treatment of RA.