State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, 650201 Kunming, China.
J Ethnopharmacol. 2025 Jan 30;337(Pt 1):118755. doi: 10.1016/j.jep.2024.118755. Epub 2024 Aug 30.
Pulmonary fibrosis (PF) is progressive and terminal lung disease, which is also the most common sequelae of Corona Virus Disease (2019) (COVID-19) survivors. Unfortunately, there is currently no cure for PF. ShaShen-MaiDong decoction (SMT), a traditional Chinese medicine, has been employed in treating various lung diseases, which may offer potential therapeutic benefits for PF.
To investigate the antifibrotic efficacy of SMT and its major active ingredients as well as the underlying mechanisms for treating PF.
Fist, we build the UPLC-MS based qualitative and quantitative profiling for the quality control of SMT. Then, the antifibrotic efficacy of SMT was investigated in bleomycin (BLM)-induced PF mice model. Network pharmacology was used to predict the mechanism and active components of SMT for the treatment of PF, which was further verified in vitro and in vivo.
SMT improved the weight loss and attenuated hydroxyproline, inflammatory cytokines, and collagen deposition in BLM-induced PF mice model in a dose-dependent manner. Mechanistically, as predicted by network pharmacology analysis, SMT and its active compounds (kaempferol, quercetin, and isorhamnetin) regulated the mitogen-activated protein kinase (MAPK) signaling pathways, TGF-β/Smad signaling pathway, and YAP/TAZ signaling pathway, which was further verified in the PF mice and TGF-β-induced A549 cell model. Moreover, SMT balanced the proportions of increased CD4 and decreased CD8 T cells in the peripheral blood of PF mice model.
Considering the high mortality and complex pathogenesis of fibrotic diseases, our results provide novel evidence that SMT would be beneficial for pulmonary fibrosis therapy by modulating MAPK, TGF-β/Smad, and YAP/TAZ signaling pathways at same time.
肺纤维化（PF）是一种进行性和终末期肺部疾病，也是 2019 年冠状病毒病（COVID-19）幸存者最常见的后遗症。不幸的是，目前 PF 没有治愈方法。沙参麦冬汤（SMT）是一种中药，已被用于治疗各种肺部疾病，可能为 PF 提供潜在的治疗益处。
研究 SMT 及其主要活性成分的抗纤维化疗效及其治疗 PF 的潜在机制。
首先，我们建立了基于 UPLC-MS 的 SMT 定性和定量分析方法，用于 SMT 的质量控制。然后，在博莱霉素（BLM）诱导的 PF 小鼠模型中研究了 SMT 的抗纤维化作用。网络药理学用于预测 SMT 治疗 PF 的机制和活性成分，并在体外和体内进行了验证。
SMT 改善了 BLM 诱导的 PF 小鼠模型中的体重减轻，并呈剂量依赖性减弱羟脯氨酸、炎症细胞因子和胶原蛋白沉积。从机制上讲，正如网络药理学分析所预测的那样，SMT 及其活性化合物（山奈酚、槲皮素和异鼠李素）调节丝裂原活化蛋白激酶（MAPK）信号通路、转化生长因子-β/ Smad 信号通路和 YAP/TAZ 信号通路，这在 PF 小鼠和转化生长因子-β诱导的 A549 细胞模型中得到了进一步验证。此外，SMT 平衡了 PF 小鼠模型外周血中增加的 CD4 和减少的 CD8 T 细胞的比例。
鉴于纤维化疾病的高死亡率和复杂发病机制，我们的结果提供了新的证据，表明 SMT 通过同时调节 MAPK、TGF-β/Smad 和 YAP/TAZ 信号通路，对肺纤维化治疗有益。
