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Identification of anti-fibrotic and pro-apoptotic bioactive compounds from Ganoderma formosanum and their possible mechanisms in modulating TGF-ß1-induced lung fibrosis.
Cheng, Kuan-Chen; Chong, Patrick Chun Theng; Hsieh, Chen-Che; Lin, Yu-Te; Ye, Chih-Hung; Khumsupan, Darin; Lu, Jheng-Jhe; Yu, Wei-Chieh; Cheng, Kai-Wen; Yap, Kah Yi; Kou, Weng Si; Cheng, Meng-Tsung; Hsu, Cheng-Chih; Sheen, Lee-Yan; Lin, Shin-Ping; Wei, An-Chi; Yu, Shu-Han.
Affiliation
  • Cheng KC; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C; Institute of Food Science Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C; Department of Optometry, Asia University, No. 500, Lioufeng Rd., Wufeng,
  • Chong PCT; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Hsieh CC; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Lin YT; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan. R.O.C.
  • Ye CH; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Khumsupan D; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Lu JJ; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Yu WC; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Cheng KW; Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Yap KY; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Kou WS; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Cheng MT; School of Pharmacy, College of Medicine, National Taiwan University, No.33, Linsen S. Rd., Taipei, 100025, Taiwan. R.O.C.
  • Hsu CC; Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C; Leeuwenhoek Laboratories Co. Ltd., No. 71, Fanglan Rd, Taipei, 106038, Taiwan. R.O.C.
  • Sheen LY; Institute of Food Science Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
  • Lin SP; School of Food Safety, Taipei Medical University, No. 250, Wu-Hsing Street, Taipei, Taiwan. R.O.C.
  • Wei AC; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan. R.O.C.
  • Yu SH; Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C. Electronic address: shuhanyu@ntu.edu.tw.
J Ethnopharmacol ; 327: 118008, 2024 Jun 12.
Article in En | MEDLINE | ID: mdl-38458343
ABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE The Compendium of Materia Medica and the Classic of Materia Medica, the two most prominent records of traditional Chinese medicine, documented the therapeutic benefits of Ganoderma sinense particularly in addressing pulmonary-related ailments. Ganoderma formosanum, an indigenous subspecies of G. sinense from Taiwan, has demonstrated the same therapeutic properties. 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. METHODS AND MATERIALS G. formosanum was fractionated into four partitions by solvents of different polarities. To determine their antifibrotic and pro-apoptotic properties, the fractions were analyzed using two TGF-ß1-induced pulmonary fibrosis cell models (NIH-3T3) and human pulmonary fibroblast cell lines, immunoblot, qRT-PCR, and annexin V assays. Subsequently, transcriptomic analysis was conducted to validate the findings and explore possible molecular pathways. The identification of potential bioactive compounds was achieved through UHPLC-MS/MS analysis, while molecular interaction study was investigated by multiple ligands docking and molecular dynamic simulations.

RESULTS:

The ethyl acetate fraction (EAF) extracted from G. formosanum demonstrated substantial anti-fibrotic and pro-apoptotic effects on TGF-ß1-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-ß receptor 1.

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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pulmonary Fibrosis / Materia Medica / Ganoderma Limits: Humans Language: En Journal: J Ethnopharmacol Year: 2024 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pulmonary Fibrosis / Materia Medica / Ganoderma Limits: Humans Language: En Journal: J Ethnopharmacol Year: 2024 Type: Article