Abstract
Rheumatoid arthritis (RA) is a type of chronic systemic inflammatory disease; it has a very complicated pathogenesis, and multiple pathological changes are implicated. Traditional Chinese medicine (TCM) like Tripterygium wilfordii Hook. F. or Sinomenium acutum (Thunb.) Rehd et Wils. has been extensively used for centuries in the treatment of arthritic diseases and been reported effective for relieving the severity of RA. Hei-Gu-Teng Zhuifenghuoluo granule (HGT) which contains Periploca forrestii Schltr., Sinomenium acutum (Thunb.) Rehd et Wils., and Lysimachia paridiformis Franch. var. stenophylla Franch. was a representative natural rattan herb formula for the treatment of RA in China, but the mechanism has not been elucidated. This study aimed at exploring the mechanism of HGT on RA using the bioinformatics analysis with in vivo and in vitro experiment validation. The potential action mechanism was first investigated by bioinformatics analysis via Ingenuity Pathway Analysis (IPA) software. After that, we use experimental validation such as collagen-induced arthritis (CIA) mice model in vivo and U937 cell model in vitro. The bioinformatics results suggested that HGT may have anti-inflammatory characteristic on RA and IL-12 signaling pathway could be the potential key trigger. In vivo experiments demonstrated that HGT ameliorated the symptoms in CIA mice and decreased the production of inflammatory cytokines in both mice ankle joints and serum. Furthermore, HGT effectively inhibited the activation of IL-12R and STAT4 on IL-12 signaling pathway. In vitro experiments showed that HGT inhibited the production of IL-12R and STAT4 induced by IL-12 in lipopolysaccharide- (LPS-) stimulated U937 cells. Moreover, IL-12R knockdown was able to interfere with the inhibition effects of HGT on the production of these cytokines. Our results confirmed the anti-inflammatory property of HGT, which was attributed to its inhibition on IL-12 signaling pathway.
Highlights
Rheumatoid arthritis (RA) which manifests as persistent and progressive joint destruction is a common chronic autoimmune disease with inflammation which leads to pain, stiffness, and the final result functional disability [1, 2]
Score for inflammation and STAT4, we examined the expression of IL-12 and STAT4 in serum and ankle joints of collagen-induced arthritis (CIA) mice
The results showed that the TNF-α levels, IL-1β levels, and IL-6 levels in the supernatant of U937 cells treated with Hei-Gu-Teng Zhuifenghuoluo granule (HGT) were inhibited both with Enzyme-Linked Immunosorbent Assay (ELISA) measurement on secretion (Figures 6(a)–6(c)) and RT-PCR measurement of mRNA (Figures 6(d)–6(f))
Summary
Rheumatoid arthritis (RA) which manifests as persistent and progressive joint destruction is a common chronic autoimmune disease with inflammation which leads to pain, stiffness, and the final result functional disability [1, 2]. Bone fusions and erosion, chronic granulation, and scar tissue result in the joints including hands and feet [3]. Traditional Chinese medicine (TCM) including herbals and herbal formulas or extracts, such as Qingfuguanjieshu, Wu Tou Tang, and extracts of the herb Tripterygium wilfordii Hook. F., is valid for alleviating the inflammation severity of RA by demonstration [4, 5]. Some natural rattan herbals can provide good therapeutic effect in RA such as Tripterygium wilfordii Hook. F. [6] and Sinomenium acutum (Thunb.) Rehd et Wils. F. [6] and Sinomenium acutum (Thunb.) Rehd et Wils. [7]; their active compounds or underlying mechanisms have always been a research trend as their main bioactive ingredient pharmacological efficacy may account for analgesic and anti-inflammatory activities [8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
