Identification of anti-fibrotic and pro-apoptotic bioactive compounds from Ganoderma formosanum and their possible mechanisms in modulating TGF-β1-induced lung fibrosis

灵芝中抗纤维化和促凋亡生物活性化合物的鉴定及其在调节 TGF-β1 诱导的肺纤维化中的可能机制

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作者:Kuan-Chen Cheng, Patrick Chun Theng Chong, Chen-Che Hsieh, Yu-Te Lin, Chih-Hung Ye, Darin Khumsupan, Jheng-Jhe Lu, Wei-Chieh Yu, Kai-Wen Cheng, Kah Yi Yap, Weng Si Kou, Meng-Tsung Cheng, Cheng-Chih Hsu, Lee-Yan Sheen, Shin-Ping Lin, An-Chi Wei, Shu-Han Yu

Aim of the study

The aim of this study is to identify bioactive compounds and evaluate the potential of G. formosanum extracts as a novel treatment to alleviate pulmonary fibrosis (PF). Using an in-house drug screening platform, two-stage screening was performed to determine their anti-fibrotic efficacy.

Conclusion

Potential bioactive compounds in G. formosanum were successfully extracted and identified in the EAF, whose anti-fibrotic and pro-apoptotic properties could potentially modulate pulmonary fibrosis. This finding not only highlights the EAF's potential as a promising therapeutic candidate to treat pulmonary fibrosis, but it also elucidates how Ganoderma confers pulmonary health benefits as described in the ancient texts.

Results

The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-β1-induced fibrotic models. Moreover, the EAF exhibited no discernible cytotoxicity. Untargeted UHPLC-MS/MS analysis identified potential bioactive compounds in EAF, including stearic acid, palmitic acid, and pentadecanoic acid. Multiple ligands docking and molecular dynamic simulations further confirmed that those bioactive compounds possess the ability to inhibit TGF-β receptor 1.

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