2. Academic Validation
  3. Ginseng and Platycodon grandiflorum ameliorated pulmonary fibrosis and inflammation targeting TLR4-P2X7r/NLRP3 signaling pathway

Ginseng and Platycodon grandiflorum ameliorated pulmonary fibrosis and inflammation targeting TLR4-P2X7r/NLRP3 signaling pathway

  • J Ethnopharmacol. 2025 May 28:348:119913. doi: 10.1016/j.jep.2025.119913.
Jia-Yi Dou 1,  Yu-Nuo Wu 2,  Chong Gao 3,  Shuang Zheng 4,  Chen-Yu Wang 5,  Xu Dai 6,  Li-Hua Lian 7,  Zhen-Yu Cui 8,  Ji-Xing Nan 9,  Yan-Ling Wu 10
Affiliations

Affiliations

  • 1 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. Electronic address: 1029103984@qq.com.
  • 2 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. Electronic address: w0601182022@163.com.
  • 3 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. Electronic address: gc161812@163.com.
  • 4 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. Electronic address: 370804487@qq.com.
  • 5 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. Electronic address: 272944954@qq.com.
  • 6 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. Electronic address: 904365657@qq.com.
  • 7 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. Electronic address: lhlian@ybu.edu.cn.
  • 8 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. Electronic address: cuizhenyu@ybu.edu.cn.
  • 9 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. Electronic address: jxnan@ybu.edu.cn.
  • 10 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. Electronic address: ylwu@ybu.edu.cn.
PMID: 40318772 DOI: 10.1016/j.jep.2025.119913
Abstract

Ethnopharmacological relevance: 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.

Aim of the study: This study investigated the protective mechanisms of ginseng and PG against pulmonary fibrosis.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Keywords

Ginseng; NLRP3; P2X7r; Platycodon grandiflorum (Jacq.) A. DC.; Pulmonary fibrosis; TLR4.

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