Yijishan Hospital, Wannan Medical College, Wuhu, China.
Key Laboratory of Non-coding RNA Transformation Research of Anhui Higher Education Institution, Wannan Medical College, Wuhu, China.
Kaohsiung J Med Sci. 2020 Jul;36(7):523-534. doi: 10.1002/kjm2.12205. Epub 2020 Mar 18.
Securidaca inappendiculata is a xanthone rich medicinal plant that has been used in the treatment of inflammation and autoimmune diseases like rheumatoid arthritis (RA) for centuries; however, the material base and mechanism of action responsible for its anti-arthritis effect still remains elusive. The objective of this study is to evaluate the therapeutic effects of xanthone-enriched extract of the plant against collagen-induced arthritis (CIA) in rats and explore the underlying mechanisms. The xanthone-deprived fraction (XDF) and xanthone-rich fraction (XRF) were obtained by using a resin adsorption coupled with acid-base treatment method, and their chemical composition difference was characterized by UPLC-MS/MS analysis. Effects of the two on CIA were analyzed using radiographic, histological, and immunohistochemical analyses. The results indicated that XRF alleviated joint structures destructions with the higher efficacy than XDF, and decreased levels of TNF-α, IL-6, and anti-cyclic citrullinated peptide antibody in CIA rats significantly. Furthermore, XRF inhibited nicotinamide phosphoribosyl transferase (NAMPT) mediated fat biosynthesis and utilization indicated by clinical evidences and metabonomics analysis, which thereby disrupted energy-metabolism feedback. In addition, Toll-like Receptor 4 and High Mobility Group Protein 1 expressions were downregulated in XRF-treated CIA rats. Collective evidences suggest NAMPT could be an ideal target for RA treatments and reveal a novel antirheumatic mechanism of S. inappendiculata by regulating NAMPT controlled fat metabolism.
翼核果是一种富含黄烷酮的药用植物，几个世纪以来，它一直被用于治疗炎症和自身免疫性疾病，如类风湿性关节炎（RA）；然而，其抗关节炎作用的物质基础和作用机制仍不清楚。本研究旨在评估该植物富含黄烷酮的提取物对胶原诱导性关节炎（CIA）大鼠的治疗作用，并探讨其潜在机制。采用树脂吸附结合酸碱处理的方法得到黄烷酮缺乏部分（XDF）和黄烷酮丰富部分（XRF），并通过 UPLC-MS/MS 分析对其化学成分差异进行了表征。采用放射学、组织学和免疫组织化学分析研究了这两部分对 CIA 的影响。结果表明，XRF 缓解了关节结构的破坏，其疗效优于 XDF，并且显著降低了 CIA 大鼠 TNF-α、IL-6 和抗环瓜氨酸肽抗体的水平。此外，XRF 抑制了烟酰胺磷酸核糖转移酶（NAMPT）介导的脂肪合成和利用，这表明其破坏了能量代谢的反馈。此外，XRF 处理 CIA 大鼠的 Toll 样受体 4 和高迁移率族蛋白 1 表达下调。综上所述，NAMPT 可作为 RA 治疗的理想靶点，并通过调节 NAMPT 控制的脂肪代谢，揭示了翼核果的一种新型抗风湿机制。
