Objectives This study aimed to reveal the anti-fibrotic effects of Botrychium ternatum (Thunb.) Sw. (BT) against idiopathic pulmonary fibrosis (IPF) and to preliminarily analyze its potential mechanism on bleomycin-induced IPF rats. Methods The inhibition of fibrosis progression in vivo was assessed by histopathology combined with biochemical indicators. In addition, the metabolic regulatory mechanism was investigated using 1H-nuclear magnetic resonance-based metabolomics combined with multivariate statistical analysis. Key findings Firstly, biochemical analysis revealed that BT notably suppressed the expression of hydroxyproline and transforming growth factor-β1 in the pulmonary tissue. Secondly, Masson’s trichrome staining and hematoxylin and eosin showed that BT substantially improved the structure of the damaged lung and significantly inhibited the proliferation of collagen fibers and the deposition of extracellular matrix. Finally, serum metabolomic analysis suggested that BT may exert anti-fibrotic effects by synergistically regulating tyrosine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; and synthesis and degradation of ketone bodies. Conclusions Our study not only clarifies the potential anti-fibrotic mechanism of BT against IPF at the metabolic level but also provides a theoretical basis for developing BT as an effective anti-fibrotic agent.

中文翻译：

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Botrychium (Thunb.) Sw 的作用机制。基于 1H-NMR 的代谢组学预防特发性肺纤维化


目的 本研究旨在揭示 Botrychium ternatum (Thunb.) Sw 的抗纤维化作用。 (BT)抗特发性肺纤维化(IPF)并初步分析其对博莱霉素诱导IPF大鼠的潜在机制。方法通过组织病理学结合生化指标评价其对体内纤维化进展的抑制作用。此外，利用基于 1H 核磁共振的代谢组学结合多变量统计分析研究了代谢调节机制。主要发现首先，生化分析表明，BT 显着抑制肺组织中羟脯氨酸和转化生长因子-β1 的表达。其次，Masson三色染色和苏木精和伊红显示BT显着改善了受损肺的结构，并显着抑制胶原纤维的增殖和细胞外基质的沉积。最后，血清代谢组学分析表明，BT可能通过协同调节酪氨酸代谢发挥抗纤维化作用；苯丙氨酸、酪氨酸和色氨酸生物合成；以及酮体的合成和降解。结论 我们的研究不仅阐明了 BT 在代谢水平上抗 IPF 的潜在抗纤维化机制，而且为将 BT 开发为有效的抗纤维化药物提供了理论基础。