Available online 7 January 2023
Author links open overlay panelAbstractBackgroundPanax 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.
MethodsAdult 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.
ResultsPPD-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.
ConclusionThese 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.
Keywords20(S)-protopanaxadiol
AMPK
pulmonary fibrosis
STING
© 2023 The Korean Society of Ginseng. Publishing services by Elsevier B.V.
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