Ginseng saponin metabolite 20(S)-protopanaxadiol relieves pulmonary fibrosis by multiple-targets signaling pathways

Journal of Ginseng Research

Available online 7 January 2023

Journal of Ginseng ResearchAuthor links open overlay panelAbstractBackground

Panax ginseng Meyer, a representative Chinese herbal medicine, can improve the body's antioxidant and anti-inflammatory capacity. 20(S)-Protopanaxadiol (PPD), an active compound isolated from ginseng, has been known to be promising pharmacological activities. However, the effect of PDD on pulmonary fibrosis has never been reported. Here, we hypothesize that PDD might reverse the inflammation-induced PF and may serve as a novel therapeutic strategy for the treatment of PF.

Methods

Adult male C57BL/6 mice were used to establish a model of pulmonary fibrosis induced by bleomycin. Lung functions were measured, along with histological and immunohistochemical examinations. Cells cultures of mouse alveolar epithelial cells were analyzed with western blotting, Co-immunoprecipitation, Immunofluorescence, immunohistochemistry, siRNA transfection, cellular thermal shift assay, qRT-PCR.

Results

PPD-treated mice exhibited a definitively improved survival rate than that of the BLM-challenged mice. Subsequently, the pulmonary fibrosis induced by BLM was markedly attenuated by PPD through reducing the expression of fibrotic hallmarks, including α-SMA, TGF-β1, fibronectin, and collagen I. Importantly, we found that BLM mice showed higher expression levels of STING in lung tissues, notably restrained by phosphorylated AMPK activated by PPD. The role of phosphorylated AMPK activated by PPD in suppressing STING was confirmed in TGF-β1-incubated cells. Notably, In vivo and in vitro analysis further indicates that treatment with PPD attenuated these aspects of bleomycin-induced pulmonary fibrosis by modulating the AMPK/STING signaling pathway.

Conclusion

These data indicate that protopanaxadiol treats bleomycin-induced PF by regulation with the multi-targets. These studies may help develop new therapeutic strategies for preventing PF.

Keywords

20(S)-protopanaxadiol

AMPK

pulmonary fibrosis

STING

© 2023 The Korean Society of Ginseng. Publishing services by Elsevier B.V.

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