College of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, PR China.
College of Life Science, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, PR China.
J Ethnopharmacol. 2022 Nov 15;298:115597. doi: 10.1016/j.jep.2022.115597. Epub 2022 Aug 5.
Hedyotis diffusa Willd, also named Scleromitrion diffusum (Willd.) R.J. Wang, is one medical herb, which has been traditionally used by the She nationality in China. And H. diffusa represents a beneficial effect on Systemic lupus erythematosus (SLE) treatment in clinic.
The underlying mechanisms of the protective effects of H. diffusa on SLE remain unclear. In this study, we treated MRL/lpr mice with H. diffusa water extract (HDW) to assess its therapeutic effects and verified its regulating signalling pathway through cytological experiments.
In the present study, the constituents of HDW were analysed through ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and SCIEX OS software. The protective activity and underlying mechanisms were studied in a MRL/lpr lupus mouse model. The blood cells, autoantibodies, metabolites and the cytokines in serum were identified with a hematology analyzer, specific ELISA kit, GC/MS system and cytometric assays. The histological and immunohistochemical analysis were engaged in the morphologic, and the expression and translocation of the crucial protein observation. The dual luciferase reporter assay was applied to identifying the regulative activity of HDW. The transcription and translation expression of the protein was studied by real-time PCR and Western blot assays. The network pharmacology analysis was employed to predict the IL-6/STAT3 pathway regulators and the screen the STAT3 inhibitors in HDW.
The results revealed the capability of HDW to attenuate the production of autoantibodies, secretion of inflammatory cytokines (IL-6 and IFN-γ), and suppressed the IgG and C3 deposition, the development of glomerular lesions in MRL/lpr mice. Serum metabolomics study showed the improvement in serum metabolites, especially aminoacyl-tRNA biosynthesis, by HDW. IL-6 was clarified to be highly associated with the significantly changed metabolites in network analysis. We further demonstrated the effects of HDW on the IL-6/STAT3 pathway in vivo and in vitro.
This study suggested that HDW exerts a therapeutic effect in SLE model mice by suppressing the IL-6/STAT3 pathway.
白花蛇舌草（Hedyotis diffusa Willd），又称节节花（Scleromitrion diffusum (Willd.) R.J. Wang），是中国畲族传统使用的一种草药。临床研究表明，白花蛇舌草对系统性红斑狼疮（SLE）有治疗作用。
白花蛇舌草对 SLE 的保护作用的潜在机制尚不清楚。在这项研究中，我们用白花蛇舌草水提取物（HDW）治疗 MRL/lpr 小鼠，以评估其治疗效果，并通过细胞学实验验证其调节信号通路。
在本研究中，我们使用超高效液相色谱/四极杆飞行时间质谱（UPLC-Q-TOF-MS）和 SCIEX OS 软件分析了 HDW 的成分。我们在 MRL/lpr 狼疮小鼠模型中研究了其保护活性和潜在机制。使用血液学分析仪、特定的 ELISA 试剂盒、GC/MS 系统和细胞检测法检测血清中的血细胞、自身抗体、代谢物和细胞因子。进行组织学和免疫组织化学分析，观察关键蛋白的表达和转位。采用双荧光素酶报告基因检测法鉴定 HDW 的调节活性。通过实时 PCR 和 Western blot 检测法研究蛋白质的转录和翻译表达。采用网络药理学分析预测 HDW 中 IL-6/STAT3 通路调节剂，并筛选 STAT3 抑制剂。
结果表明，HDW 能够减轻 MRL/lpr 小鼠自身抗体的产生、炎症细胞因子（IL-6 和 IFN-γ）的分泌，并抑制 IgG 和 C3 的沉积，改善肾小球病变。血清代谢组学研究表明，HDW 能改善血清代谢物，特别是氨基酸酰基-tRNA 生物合成。网络分析表明，IL-6 与显著变化的代谢物高度相关。我们进一步证实了 HDW 在体内和体外对 IL-6/STAT3 通路的影响。
本研究表明，HDW 通过抑制 IL-6/STAT3 通路对 SLE 模型小鼠发挥治疗作用。
