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, Taichung, Taiwan. R.O.C; Department of Medical Research, China Medical University Hospital, China Medical University, No. 91, Hsueh-Shih Rd., Taichung, Taiwan. R.O.C.
Institute of Biotechnology, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei, Taiwan. R.O.C.
J Ethnopharmacol. 2024 Jun 12;327:118008. doi: 10.1016/j.jep.2024.118008. Epub 2024 Mar 6.
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.
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.
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-β1-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.
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.
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.
《本草纲目》和《本草纲目》是中医最著名的两部典籍，记载了灵芝对肺部疾病的治疗作用。台湾本土灵芝亚种——台湾灵芝，具有相同的治疗特性。
本研究旨在鉴定灵芝中的生物活性化合物，并评估灵芝提取物作为一种新型治疗方法缓解肺纤维化（PF）的潜力。使用内部药物筛选平台，进行两阶段筛选以确定其抗纤维化功效。
灵芝用不同极性溶剂分为四部分。为了分析其抗纤维化和促凋亡特性，用两种 TGF-β1 诱导的肺纤维化细胞模型（NIH-3T3）和人肺成纤维细胞系进行分析，免疫印迹、qRT-PCR 和 Annexin V 检测。随后，进行转录组分析以验证研究结果并探索可能的分子途径。通过 UHPLC-MS/MS 分析鉴定潜在生物活性化合物，通过多配体对接和分子动力学模拟研究分子相互作用。
灵芝的乙酸乙酯提取物（EAF）对 TGF-β1 诱导的纤维化模型具有显著的抗纤维化和促凋亡作用。此外，EAF 没有明显的细胞毒性。非靶向 UHPLC-MS/MS 分析鉴定出 EAF 中的潜在生物活性化合物，包括硬脂酸、棕榈酸和十五烷酸。多配体对接和分子动力学模拟进一步证实这些生物活性化合物具有抑制 TGF-β 受体 1 的能力。
灵芝中的潜在生物活性化合物已成功从 EAF 中提取和鉴定，其抗纤维化和促凋亡特性可能调节肺纤维化。这一发现不仅突出了 EAF 作为治疗肺纤维化的潜在治疗候选物的潜力，还阐明了灵芝如何如古代文献所述，赋予肺部健康益处。
