School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, PR China; Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, PR China.
Department of Hepatology, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, PR China.
J Ethnopharmacol. 2025 Jan 10;336:118661. doi: 10.1016/j.jep.2024.118661. Epub 2024 Aug 17.
Shuangdan Jiedu Decoction (SJD) is a formula composed of six Chinese herbs with heat-removing and detoxifying, antibacterial, and anti-inflammatory effects, which is clinically used in the therapy of various inflammatory diseases of the lungs including COVID-19, but the therapeutic material basis of its action as well as its molecular mechanism are still unclear.
The study attempted to determine the therapeutic effect of SJD on LPS-induced acute lung injury (ALI), as well as to investigate its mechanism of action and assess its therapeutic potential for the cure of inflammation-related diseases in the clinical setting.
We established an ALI model by tracheal drip LPS, and after the administration of SJD, we collected the bronchoalveolar lavage fluid (BALF) and lung tissues of mice and examined the expression of inflammatory factors in them. In addition, we evaluated the effects of SJD on the cyclic guanosine monophosphate-adenosine monophosphate synthase -stimulator of interferon genes (cGAS-STING) and inflammasome by immunoblotting and real-time quantitative polymerase chain reaction (RT-qPCR).
We demonstrated that SJD was effective in alleviating LPS-induced ALI by suppressing the levels of pro-inflammatory cytokines in the BALF, improving the level of lung histopathology and the number of neutrophils, as well as decreasing the inflammatory factor-associated gene expression. Importantly, we found that SJD could inhibit multiple stimulus-driven activation of cGAS-STING and inflammasome. Further studies showed that the Chinese herbal medicines in SJD had no influence on the cGAS-STING pathway and inflammasome alone at the formulated dose. By increasing the concentration of these herbs, we observed inhibitory effects on the cGAS-STING pathway and inflammasome, and the effect exerted was maximal when the six herbs were combined, indicating that the synergistic effects among these herbs plays a crucial role in the anti-inflammatory effects of SJD.
Our research demonstrated that SJD has a favorable protective effect against ALI, and its mechanism of effect may be associated with the synergistic effect exerted between six Chinese medicines to inhibit the cGAS-STING and inflammasome abnormal activation. These results are favorable for the wide application of SJD in the clinic as well as for the development of drugs for ALI from herbal formulas.
双丹解毒汤（SJD）是一种由六种草药组成的配方，具有清热解毒、抗菌和抗炎作用，临床上用于治疗包括 COVID-19 在内的各种肺部炎症性疾病，但它的作用治疗物质基础及其分子机制尚不清楚。
本研究试图确定 SJD 对 LPS 诱导的急性肺损伤（ALI）的治疗作用，以及探讨其作用机制，并评估其在临床治疗炎症相关疾病方面的治疗潜力。
我们通过气管滴注 LPS 建立了 ALI 模型，给予 SJD 后，收集小鼠的支气管肺泡灌洗液（BALF）和肺组织，检测其中炎症因子的表达。此外，我们通过免疫印迹和实时定量聚合酶链反应（RT-qPCR）评估了 SJD 对环鸟苷酸-腺苷酸合酶-干扰素基因刺激物（cGAS-STING）和炎症小体的影响。
我们证明 SJD 通过抑制 BALF 中促炎细胞因子的水平，改善肺组织病理学水平和中性粒细胞数量，降低炎症因子相关基因表达，有效缓解 LPS 诱导的 ALI。重要的是，我们发现 SJD 可以抑制多种刺激物驱动的 cGAS-STING 和炎症小体的激活。进一步的研究表明，SJD 中的草药在制定剂量下单独作用于 cGAS-STING 途径和炎症小体时没有影响。增加这些草药的浓度，我们观察到对 cGAS-STING 途径和炎症小体的抑制作用，当六种草药联合使用时效果最大，表明这些草药之间的协同作用在 SJD 的抗炎作用中起着关键作用。
我们的研究表明，SJD 对 ALI 具有良好的保护作用，其作用机制可能与六种中药协同抑制 cGAS-STING 和炎症小体异常激活有关。这些结果有利于 SJD 在临床上的广泛应用，也有利于从草药配方中开发用于治疗 ALI 的药物。
