Chlorogenic acid induces apoptosis to inhibit inflammatory proliferation of IL-6-induced fibroblast-like synoviocytes through modulating the activation of JAK/STAT and NF-κB signaling pathways

Abstract

Chlorogenic acid (CGA) is the primary constituent of Caulis , a Chinese herb used for the treatment of rheumatoid arthritis (RA). The present study aimed to investigate whether CGA was able to inhibit the proliferation of the fibroblast-like synoviocyte cell line (RSC-364), stimulated by interleukin (IL)-6, through inducing apoptosis. Following incubation with IL-6 or IL-6 and CGA, the cellular proliferation of RSC-364 cells was detected by MTT assay. The ratio of apoptosed cells were detected by flow cytometry. Western blot analysis was performed to observe protein expression levels of key molecules involved in the Janus-activated kinase/signal transducer and activator of transcription 3 (JAK/STAT) signaling pathway [phosphorylated (p)-STAT3, JAK1 and gp130] and the nuclear factor κB (NF-κB) signaling pathway [phosphorylated (p)-inhibitor of κB kinase subunit α/β and NF-κB p50). It was revealed that CGA was able to inhibit the inflammatory proliferation of RSC-364 cells mediated by IL-6 through inducing apoptosis. CGA was also able to suppress the expression levels of key molecules in the JAK/STAT and NF-κB signaling pathways, and inhibit the activation of these signaling pathways in the inflammatory response through IL-6-mediated signaling, thereby resulting in the inhibition of the inflammatory proliferation of synoviocytes. The present results indicated that CGA may have potential as a novel therapeutic agent for inhibiting inflammatory hyperplasia of the synovium through inducing synoviocyte apoptosis in patients with RA.

Alleviation of Synovial Inflammation of Juanbi-Tang on Collagen-Induced Arthritis and TNF-Tg Mice Model

“…As a detectable component of JBT, gentiopicroside also exhibited a potent protective effect on the IL-1b-induced inflammatory response and the release of MMPs in rat articular chondrocytes by the p38, ERK, and JNK pathways (Zhao et al, 2015). Chlorogenic acid was reported to reverse IL-1binduced increases in IL-6, MMP-13, and COX-2/PGE2 production in human SW1353 chondrocytes, partially via the p65 NF-kappa B signaling pathway (Liu et al, 2017), and to induce apoptosis to inhibit the inflammatory proliferation of IL-6-induced FLSs through modulating the activation of the JAK/STAT and NFkappa B signaling pathways (Lou et al, 2016). Moreover, isoliquiritigenin treatment inhibited IL-1b-induced MMP production and NF-kappa B activation both in vitro and in vivo .…”

Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis mice

“…Additionally, previous studies from our laboratory suggested that the optimized formula of XFHM has inhibitory effects on apoptosis of lymphocytes in rats with adjuvant arthritis [16]. In previous studies, we discovered that chlorogenic acid and Luteolin, the main components of Caulis Lonicerae Japonicae (the monarch drug in XFHM), can inhibit the inflammatory proliferation of rat synovial cells induced by IL-1β [17] and IL-6 [18]. In addition, several studies have indicated that both the crude herbs and the active ingredients of these herbs have beneficial effects on RA.…”

A network pharmacology-based analysis to distinguish the differences between Lonicerae Japonicae Flos and Lonicerae Flos

“…The extract of LF blocks the activation of the NF-κB in ammatory signalling pathway by inhibiting IκBα phosphorylation with NF-κB p65 and IκBα degradation [30]. The extract of LJF substantially reduces p50 and IKK expression levels on the NF-κB pathway [31]. Therefore, LJF and LF act synergistically on the NF-κB signalling pathway but under different mechanisms.…”