Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.
Department of Rheumatology, The First Affiliated Hospital, Anhui University of Chinese Medicine, Hefei, China; Institute of Rheumatism, Anhui University of Chinese Medicine, Hefei, China.
J Ethnopharmacol. 2023 Feb 10;302(Pt A):115886. doi: 10.1016/j.jep.2022.115886. Epub 2022 Nov 4.
Huangqin Qingre Qubi Capsule (HQC) is a Chinese herbal compound for the treatment of rheumatoid arthritis (RA), which is made from dry roots of Scutellaria baicalensis Georgi, dry mature seeds of Gardenia jasminoides J.Ellis, dry and mature seeds of Coix lacryma-jobi var. stenocarpa Oliv., dry mature seeds of Amygdalus persica L. and roots and rhizomes of Clematis chinensis Osbeck in the proportion of 10:9:30:5:10. HQC has a significant effect in clinical treatment of RA, which can inhibit RA inflammation, improve oxidative stress state, and effectively relieve symptoms of RA patients.
The anti-arthritis effect of HQC and its mechanism, especially whether it improves RA through FZD8-Wnt/β-catenin signal axis, were studied using adjuvant arthritis (AA) rats and FLS from RA patients.
Real time qPCR (RT-qPCR), Western blot (WB), confocal microscopy and other molecular biological methods were used to study the anti-RA effect of HQC and its mechanism.
The expression of FZD8 was significantly up-regulated in synovium and FLS of AA rats and RA FLS. FZD8 significantly activated the Wnt/β-catenin signaling pathway, promoted abnormal proliferation of FLS, increased the levels of inflammatory factors IL-1β, IL-6 and IL-8, and significantly increased the expression of matrix metalloproteinase 3 (MMP3) and fibronectin. HQC has significant therapeutic effect on AA rats. Molecular docking and molecular dynamics showed that HQC had a good binding ability with FZD8. We also confirmed that HQC inhibited Wnt/β-catenin signaling pathway by binding FZD8, and reduced the levels of the above inflammatory factors and pathological genes of RA.
The expression of FZD8 is significantly increased in AA rats and FLS from RA patients. Clarify that HQC improves RA through the FZD8-Wnt/β-catenin signal axis, provide a clear therapeutic mechanism for HQC to improve RA, and also provide a basis for clinical promotion of HQC.
黄芩清热去湿胶囊（HQC）是一种用于治疗类风湿关节炎（RA）的中草药复方，由黄芩根、栀子干成熟种子、薏苡仁干成熟种子、苦杏仁干成熟种子和川木通根和根茎以 10:9:30:5:10 的比例制成。HQC 在 RA 的临床治疗中具有显著效果，可抑制 RA 炎症，改善氧化应激状态，有效缓解 RA 患者的症状。
本研究采用佐剂关节炎（AA）大鼠和 RA 患者的成纤维样滑膜细胞（FLS），研究 HQC 的抗关节炎作用及其机制，特别是其是否通过 FZD8-Wnt/β-catenin 信号轴改善 RA。
采用实时 qPCR（RT-qPCR）、Western blot（WB）、共聚焦显微镜等分子生物学方法研究 HQC 的抗 RA 作用及其机制。
FZD8 在 AA 大鼠滑膜和 FLS 以及 RA FLS 中的表达均显著上调。FZD8 显著激活 Wnt/β-catenin 信号通路，促进 FLS 异常增殖，增加 IL-1β、IL-6 和 IL-8 等炎症因子水平，显著增加基质金属蛋白酶 3（MMP3）和纤维连接蛋白的表达。HQC 对 AA 大鼠具有显著的治疗作用。分子对接和分子动力学表明，HQC 与 FZD8 具有良好的结合能力。我们还证实，HQC 通过与 FZD8 结合抑制 Wnt/β-catenin 信号通路，降低 RA 上述炎症因子和病理基因的水平。
FZD8 在 AA 大鼠和 RA 患者的 FLS 中表达显著增加。阐明 HQC 通过 FZD8-Wnt/β-catenin 信号轴改善 RA，为 HQC 改善 RA 提供明确的治疗机制，也为 HQC 的临床推广提供依据。
