Chlorogenic acid and luteolin synergistically inhibit the proliferation of interleukin-1β-induced fibroblast-like synoviocytes through regulating the activation of NF-κB and JAK/STAT-signaling pathways

Abstract

Our finding suggested that the combination of CGA and Lut may be a potential therapeutic treatment for the inflammatory proliferation of synoviocytes in patients with RA.

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

“…Isoimperatorin can inhibit TNFα-induced expression of VCAM-1 by up-regulating the production of PPAR-γ and translating signals to ERK1/2, PI3K, and PKC [42]. Chlorogenic acid [17] and Caffeic acid [43] have inhibitory effects on the inflammatory proliferation of synoviocytes. Wogonin can down-regulate the production of MMP-3, acting directly on articular chondrocytes [44].…”

“…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.…”

Red nucleus interleukin‐1β evokes tactile allodynia through activation of JAK/STAT3 and JNK signaling pathways

“…IL‐1β induces cellular responses by combining with its specific receptor IL‐1RI, and then recruits a coreceptor chain involving the accessory protein (IL‐1RAcP) and the adaptor protein myeloid differentiation primary response gene 88 (MyD88) to bind to the Toll‐IL‐1 receptor (TIR) domain, leading to a series of phosphorylation events and promoting the subsequent activation of various signaling pathways (Dinarello, ; Garlanda et al, ). Numerous studies have demonstrated that IL‐1β activates the JAK/STAT signaling pathway after combining with IL‐1RI, and induces JAK‐mediated phosphorylation of STAT proteins (Li et al, ; Lou et al, ; Saleh et al, ; Tanabe, Kozawa, & Iida, ; Tanabe, Nishimura, Dohi, & Kozawa, ). It has been verified that IL‐1β can trigger the activation of the JAK/STAT3 signaling pathway, through which it augments neurite outgrowth (Saleh et al, ), stimulates the proliferation of fibroblast‐like synoviocytes (Lou et al, ), and induces the expression of IL‐6 and glial cell line‐derived neurotrophic factor (GDNF) in rat C6 glioma cells (Tanabe et al, ; Tanabe, Kozawa, & Iida, ).…”

“…Numerous studies have demonstrated that IL‐1β activates the JAK/STAT signaling pathway after combining with IL‐1RI, and induces JAK‐mediated phosphorylation of STAT proteins (Li et al, ; Lou et al, ; Saleh et al, ; Tanabe, Kozawa, & Iida, ; Tanabe, Nishimura, Dohi, & Kozawa, ). It has been verified that IL‐1β can trigger the activation of the JAK/STAT3 signaling pathway, through which it augments neurite outgrowth (Saleh et al, ), stimulates the proliferation of fibroblast‐like synoviocytes (Lou et al, ), and induces the expression of IL‐6 and glial cell line‐derived neurotrophic factor (GDNF) in rat C6 glioma cells (Tanabe et al, ; Tanabe, Kozawa, & Iida, ). Blockade of the JAK/STAT3 signaling significantly suppresses the effects of IL‐1β.…”

Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction

“…FLS plays an essential role in the development of synovial inflammation of RA (Li et al, ). Triptolide, celastrol, geniposide, paeoniflorin, clematichinenoside AR, kirenol, tanshinone IIA, bauchampine A, baicalein, 1,7‐dihydroxyl‐3,4‐dimethoxylxanthone, catechin, licochalcone A, luteolin, quercetin, ramosissimin, α‐mangostin, berberine, fissistigmine A, matrine, norisoboldine, sinomenine, tamaractam, caffeic acid, paeonol, chlorogenic acid, and daphnetin have been reported to induce apoptosis of FLS or inhibit its proliferation (Bi, Xin, Gao, Lin, & Qian, ; Chen et al, ; Chen et al, ; Hong et al, ; Hua et al, ; Jie et al, ; Kusunoki et al, ; Li et al, ; Liu et al, ; Liu, Feng, Wang, Zhao, & Li, ; Lou et al, ; Luo et al, ; Pan, Zhu, Lv, & Pei, ; Shu et al, ; Su et al, ; Su, Sun, Ao, & Zhao, ; Sun et al, ; Sun, Ding, & Yao, ; Sung et al, ; Tang, Wei, & Wang, ; Wang et al, ; Wang, Jiang, & Sun, ; Wang, Sun, & Jin, ; Xu et al, ; Yang, Dong, & Li, ; Yao et al, ; Yi et al, ; Zhang et al, ; Zhang et al, ; Zheng, Wei, Zhu, & Liu, ; Zhou et al, ; Zuo, Xia, Li, Ou‐Yang, & Chen, ). Some previous researches have shown that betulinic acid, kaempferol, leonurine, oxymatrine, and piperlongumine can inhibit the migration and invasion of FLS in RA models (Li et al, ; Liang et al, ; Liu, Feng, et al, ; Pan et al, ; Sun, Xu, Du, Zhang, & Zhu, ).…”