Ren Mingyue, Sun Mengmeng, Zhang Bingxue, Peng Minghao, Song Guihua
Department of Pediatrics, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan, China.
School of Pediatrics, Henan University of Chinese Medicine, Zhengzhou, Henan, China.
Inflamm Res. 2025 Sep 16;74(1):129. doi: 10.1007/s00011-025-02094-5.
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.
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.
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.
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.
小青龙汤是一种传统中药。加味小青龙汤（M-XQLD）是在小青龙汤的基础上加用黄芪和党参而成。临床试验表明M-XQLD治疗哮喘有效，但目前其治疗哮喘的机制尚不清楚。
用卵清蛋白（OVA）致敏小鼠以诱导哮喘。通过灌胃给予M-XQLD。采用无标记蛋白质组学方法鉴定M-XQLD的下游靶点。进行组织病理学评估、支气管肺泡灌洗液（BALF）中多种细胞因子检测。在体外，分离初始CD4 + T细胞进行分析。
OVA刺激降低了含StAR相关脂质转移结构域13（STARD13）的表达，而M-XQLD治疗可使其表达增加。STARD13过表达减少了炎性细胞浸润和杯状细胞。STARD13过表达降低了血清和BALF中OVA特异性IgE、IL-4和IL-5的水平。STARD13过表达抑制了IL-1β、IL-17A和IL-22的表达，并减少了Th17分化。STARD13过表达抑制了RhoA/ROCK2，而敲低STARD13导致RhoA持续激活。此外，STARD13过表达降低了p38磷酸化水平。SB203580处理进一步抑制了RORC表达和p38磷酸化。更重要的是，敲低STARD13显著降低了M-XQLD对OVA诱导小鼠的治疗效果。
本研究表明M-XQLD作用于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。
