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

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.