Dou Jia-Yi, Wu Yu-Nuo, Gao Chong, Zheng Shuang, Wang Chen-Yu, Dai Xu, Lian Li-Hua, Cui Zhen-Yu, Nan Ji-Xing, Wu Yan-Ling
Key Laboratory for Traditional Chinese Korean Medicine Research (State Ethnic Affairs), Key Laboratory of Natural Medicines of the Changbai Mountain (Ministry of Education), College of Pharmacy, Yanbian University, Yanji, Jilin Province, 133002, PR China.
J Ethnopharmacol. 2025 May 28;348:119913. doi: 10.1016/j.jep.2025.119913. Epub 2025 May 1.
Ginseng and Platycodon grandiflorum (Jacq.) A. DC. (PG) are traditional Chinese herb medicine and classified into the lung meridian, which traditionally used to treat respiratory disorders.
This study investigated the protective mechanisms of ginseng and PG against pulmonary fibrosis.
Panax ginseng C.A.Mey. (GS), Ginseng Radix et Rhizoma Rubra (RGR), PG and GS + PG extracts were prepared using aqueous or ethanol extraction methods and analyzed by HPLC. Cigarette smoke (CS)-induced pulmonary fibrosis mice were administrated with GS, RGR, PG, GS + PG aqueous extracts or platycodin D (PD, the major active component of PG), respectively. A549 were stimulated with different stimulators TGF-β, LPS + ATP or conditioned medium from LPS-primed THP-1 (CM), then cultured with PG, PD or A438079 (P2X7r antagonist), respectively.
In CS-exposed mice, GS, RGR, PG, or GS + PG extracts significantly reduced lung index elevation without effects on kidney, cardiac or liver indices. These extracts ameliorated CS-induced alveolar wall thickening, extracellular matrix (ECM) accumulation, inflammation, and inhibited P2X7r/NLRP3, TLR4/IRAK4, and NF-κB/IκB-α. PG or PD significantly alleviated lung injury and ECM deposition in CS-exposed mice. PG or PD inhibited CS-induced inflammatory cytokine secretion and immune cell recruitment by TLR4-P2X7r/NLRP3 blockade. In CM-stimulated A549, PG or PD significantly reduced ECM accumulation and inflammatory factors release. PG blocked CM-triggered TLR4-P2X7r/NLRP3 activation in A549, with similar functioning as A438079.
GS and PG ameliorated pulmonary fibrosis via TLR4-P2X7r/NLRP3. PG and PD regulated cell crosstalk in alveolar microenvironment against pulmonary injury, which might be novel therapeutic strategy for pulmonary fibrosis.
人参和桔梗是传统的中草药，归肺经，传统上用于治疗呼吸系统疾病。
本研究探讨人参和桔梗对肺纤维化的保护机制。
采用水提或醇提方法制备人参、红参、桔梗及人参+桔梗提取物，并通过高效液相色谱法进行分析。将香烟烟雾（CS）诱导的肺纤维化小鼠分别给予人参、红参、桔梗、人参+桔梗水提取物或桔梗皂苷D（PD，桔梗的主要活性成分）。用不同刺激物转化生长因子-β（TGF-β）、脂多糖（LPS）+三磷酸腺苷（ATP）或来自经LPS预处理的单核细胞增多症患者THP-1的条件培养基（CM）刺激人肺腺癌A549细胞，然后分别用桔梗、PD或A438079（P2X7受体拮抗剂）进行培养。
在暴露于CS的小鼠中，人参、红参、桔梗或人参+桔梗提取物显著降低了肺指数升高，而对肾脏、心脏或肝脏指数无影响。这些提取物改善了CS诱导的肺泡壁增厚、细胞外基质（ECM）积聚、炎症，并抑制了P2X7受体/核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）、Toll样受体4（TLR4）/白细胞介素-1受体相关激酶4（IRAK4）和核因子κB（NF-κB）/核因子κB抑制蛋白α（IκB-α）。桔梗或PD显著减轻了暴露于CS的小鼠的肺损伤和ECM沉积。桔梗或PD通过阻断TLR4-P2X7r/NLRP3抑制CS诱导的炎性细胞因子分泌和免疫细胞募集。在CM刺激的A549细胞中，桔梗或PD显著减少了ECM积聚和炎性因子释放。桔梗阻断了CM触发的A549细胞中TLR4-P2X7r/NLRP3激活，其功能与A438079相似。
人参和桔梗通过TLR4-P2X7r/NLRP3改善肺纤维化。桔梗和PD调节肺泡微环境中的细胞串扰以对抗肺损伤，这可能是肺纤维化的新治疗策略。
