Mechanism of action of M-XQLD treatment for asthma: role of STARD13 in Th17 suppression.

IF 5.4 3区医学 Q2 CELL BIOLOGY

Inflammation Research Pub Date : 2025-09-16 DOI:10.1007/s00011-025-02094-5

Mingyue Ren, Mengmeng Sun, Bingxue Zhang, Minghao Peng, Guihua Song

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Abstract

Objective: Xiaoqinglong Decoction (XQLD) is a traditional oriental medicine. Modified- Xiaoqinglong Decoction (M-XQLD) was established by adding astragalus membranaceus and codonopsis pilosula on the basis of XQLD. M-XQLD has been shown to be effective in therapying asthma in clinical trials, but the mechanism of M-XQLD in asthma is currently unknown.

Methods: Mice were sensitized by ovalbumin (OVA) to induce asthma. M-XQLD were administered by oral gavage. Label-free proteomics was conducted to identify the downstream target of M-XQLD. Histopathological assessment, multiple cytokine examination in bronchoalveolar lavage fluid (BALF) were conducted. In vitro, we isolated Naïve CD4 + T cells for analysis.

Results: OVA stimulation decreased the expression of StAR Related Lipid Transfer Domain Containing 13 (STARD13), while M-XQLD treatment increased it. STARD13 overexpression reduced the inflammatory cell infiltration and goblet cells. STARD13 overexpression reduced the levels of OVA-specific IgE, IL-4, and IL-5 in serum and BALF. STARD13 overexpression inhibited the expression of IL-1β, IL-17A, and IL-22, and reduced Th17 differentiation. STARD13 overexpression inhibited the RhoA/ROCK2, while knockdown of STARD13 resulted in continuous activation of RhoA. Furthermore, STARD13 overexpression decreased p38 phosphorylation level. SB203580 treatment further inhibited the RORC expression and p38 phosphorylation. More importantly, the therapeutic efficacy of M-XQLD in OVA-induced mice was significantly reduced by STARD13 knockdown.

Conclusions: This study revealed that M-XQLD targets to STARD13, and highlighted that STARD13 alleviated asthma by reducing Th17 differentiation via inhibiting the RhoA/ROCK2/p38 signaling.

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M-XQLD治疗哮喘的作用机制：STARD13在Th17抑制中的作用

目的：小青龙汤是一种中药。在小青龙汤的基础上，加入黄芪、党参，建立了小青龙汤的加减配方。M-XQLD已在临床试验中显示出治疗哮喘的有效性，但M-XQLD治疗哮喘的机制目前尚不清楚。方法：用卵清蛋白致敏小鼠诱导哮喘。M-XQLD灌胃给药。利用无标签蛋白质组学技术鉴定M-XQLD的下游靶点。进行组织病理学评估和支气管肺泡灌洗液（BALF）多种细胞因子检测。我们在体外分离Naïve CD4 + T细胞进行分析。结果：卵细胞刺激降低了StAR相关脂质转移域13 （StAR Related脂质转移域13，STARD13）的表达，而M-XQLD使其表达升高。STARD13过表达可减少炎症细胞浸润和杯状细胞。STARD13过表达降低了ova特异性IgE、IL-4和IL-5在血清和BALF中的水平。STARD13过表达抑制IL-1β、IL-17A、IL-22的表达，抑制Th17的分化。STARD13过表达抑制RhoA/ROCK2，而STARD13的下调导致RhoA持续激活。此外，STARD13过表达降低了p38磷酸化水平。SB203580处理进一步抑制RORC表达和p38磷酸化。更重要的是，敲低STARD13显著降低M-XQLD对ova诱导小鼠的治疗效果。结论：本研究发现M-XQLD靶向STARD13，并强调STARD13通过抑制RhoA/ROCK2/p38信号通路减少Th17分化，从而减轻哮喘。

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来源期刊

Inflammation Research 医学-免疫学

CiteScore

9.90

自引率

1.50%

发文量

134

审稿时长

3-8 weeks

期刊介绍： Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.