Total alkaloids of Bulbus Fritillariae Pallidiflorae alleviated silica induced pulmonary inflammation and fibrosis via regulating EMT and TGF-β1/Smad signaling pathway.

Abstract

Silicosis is an interstitial lung disease caused by long-term exposure to an environment containing silica, characterized primarily by chronic inflammation and progressive fibrosis. Due to its complex pathogenesis, lung transplantation is the only curative treatment. Therefore, there is an urgent need to explore new and effective therapeutic drugs. Previous studies have shown that total alkaloids of Bulbus Fritillariae Pallidiflorae (TA-BFP) exhibit favorable anti-inflammatory, antioxidant, and anti-fibrotic activities. Thus, we hypothesize that TA-BFP may be a potential drug for the treatment of silicosis. In the present study, by constructing a silica-induced silicosis mouse model, it was found that the level of inflammatory factors in the serum and the degree of fibrosis in the lung tissues of the mice increased with the increase of exposure time. By prophylactic administration of TA-BFP intervention, the levels of inflammatory factors in serum and the expression of HYP, collagen I and collagen III in lung tissues were down-regulated in mice. To explore the underlying mechanism of action, based on the results of network pharmacology analysis, the expression of proteins related to the epithelial-mesenchymal transition (EMT) and TGF-β1/Smad signaling pathway was detected. We found that TA-BFP intervention inhibited the TGF-β1/Smad pathway and reversed the EMT process. In addition, TA-BFP inhibited cell migration in a dose-dependent manner in an in vitro constructed EMT model of A549 cells. In summary, the findings of this study demonstrate that TA-BFP can effectively ameliorate the development of silicosis, and its potential mechanism of action may be related to the intervention of the TGF-β1/Smad pathway and the EMT process. This provides a novel concept for the rational utilization of ibogaine and the clinical treatment of silicosis.

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