Jatrorrhizine Hydrochloride Suppresses Proliferation, Migration, and Secretion of Synoviocytes In Vitro and Ameliorates Rat Models of Rheumatoid Arthritis In Vivo

Abstract

Jatrorrhizine hydrochloride (JH), an active component isolated from the traditional Chinese herb Coptis chinensis, has been reported to have antimicrobial, antitumor, antihypercholesterolemic, and neuroprotective activities. However, its antirheumatoid arthritis (RA) property remains unknown. In this study, a collagen-induced arthritis (CIA) rat model was used to evaluate the therapeutic effects of JH on RA by using arthritis score, radiological evaluation, and histopathological assessment. The in vitro effects of JH on proliferation, migration, and production of inflammatory mediators in RA-derived fibroblast-like synoviocyte MH7A cells were determined by the EdU incorporation assay, wound healing assay, real-time PCR, and ELISA, respectively. The in vivo studies showed that JH treatment significantly prevented the progression and development of RA in CIA rats through anti-inflammation and suppressing bone destruction. The in vitro studies revealed that JH could effectively attenuate the destructive phenotypes of MH7A cells, including inhibiting proliferation, migration, and production of inflammatory mediators. Further mechanistic analysis demonstrated that JH suppressed tumor necrosis factor alpha (TNFα)-stimulated activations of nuclear factor of kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) (ERK and p38) leading to the downregulation of proinflammatory cytokines, which might be beneficial to the antiproliferative and antimigratory activities of FLS cells. Collectively, our results demonstrated that JH has a great potential to be developed into a novel therapeutic agent for treating RA.

Kuijieyuan Decoction Improved Intestinal Barrier Injury of Ulcerative Colitis by Affecting TLR4-Dependent PI3K/AKT/NF-κB Oxidative and Inflammatory Signaling and Gut Microbiota

“…Palmatine displays anti-inflammatory function by inhibiting TRIF-dependent NF-κB ( Yan et al., 2017 ). Jatrorrhizine suppresses proliferation, migration, and secretion of synoviocytes in an animal model with rheumatoid arthritis ( Qiu et al., 2018 ). Baicalein exerts anti-inflammatory function by inhibiting NF-κB transactivation ( Patwardhan et al., 2016 ).…”

Jatrorrhizine Hydrochloride Suppresses RANKL-Induced Osteoclastogenesis and Protects against Wear Particle-Induced Osteolysis

“…In our study, JH did not affect JNK and NF-κB signaling pathways, however, it could significantly suppress the phosphorylation levels of RANKL-mediated p38 and ERK. Interestingly, our previous study showed that, in synoviocyte cell line MH7A, JH also significantly inhibited TNFα-induced p38 and ERK activation [ 23 ]. Thus, it is possible that blocking p38 and ERK activation might be an important active site of JH.…”

“…Nevertheless, to our knowledge, no study has investigated its anti-osteoclastogenic and anti-resorptive actions. In our recently published paper, JH has been demonstrated to inhibit focal bone erosion in collagen-induced arthritis (CIA) rat model [ 23 ]. As osteoclast is the sole cell type responsible for bone resorption, therefore, we speculated that JH may have a potential therapeutic role of anti-osteolytic diseases through inhibiting osteoclastogenesis.…”

Huang-Lian-Jie-Du Decoction Ameliorates Acute Ulcerative Colitis in Mice via Regulating NF-κB and Nrf2 Signaling Pathways and Enhancing Intestinal Barrier Function

“…We searched the literature related to the pharmacological mechanism of these 13 active ingredients. Encouragingly, the literature shows that 12 active ingredients could exert anti-inflammatory effects by inhibiting the NF-κB signaling pathway (Sun et al, 2015b; Li et al, 2016b; Wang et al, 2016b; Yan et al, 2017; Chen et al, 2017a; Chen et al, 2017b; Chen et al, 2018; Guo et al, 2018; Qiu et al, 2018; Lu et al, 2019; Luan et al, 2019; Pan et al, 2019), while only 8 active components exert antioxidant effects by activating the Nrf2 signaling pathway (Li et al, 2016a; Chen et al, 2018; Fang et al, 2018; Luo et al, 2018; Wang et al, 2018; Chen et al, 2019; Jia et al, 2019; Jiang et al, 2019) ( Figure 11 ). Besides, there are six active ingredients that exert mucosal protective effects by restoring tight junction protein expression (Zhu et al, 2012; Bribi et al, 2016; Ruan et al, 2016; Chen et al, 2017a; Peng et al, 2018; Yu et al, 2018) ( Figure 11 ).…”