Mechanisms exploration of terrestrosin D on pulmonary fibrosis based on plasma metabolomics and network pharmacology.

Terrestrosin D (TED) is the active ingredient of Tribulus terrestris L., which is used in traditional Chinese medicine (TCM) formulations and has a wide range of pharmacological activities. A previous study showed that TED alleviated bleomycin (BLM)-induced pulmonary fibrosis (PF) in mice. However, the mechanisms underlying the therapeutic effect of TED are still unclear and need further investigation. In this study, we evaluated the effect of TED in a mice of BLM-induced PF in terms of histopathological and biochemical indices. UHPLC-MS-based plasma metabolomics combined with network pharmacology was used to explore the pathological basis of PF and the mechanism of action of TED. Histological and biochemical analyses showed that TED mitigated inflammatory injury in the lungs, especially at the dosage of 20 mg/kg. Furthermore, BLM changed the plasma metabolite profile in the mice, which was reversed by TED via regulation of amino acid and lipid metabolism. Subsequently, a biomarkers-targets-disease network was constructed, and tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 were identified as the putative therapeutic targets of TED. Both factors were quantitatively analyzed using enzyme-linked immunosorbent assay (ELISA). Taken together, the combination of UHPLC-MS-based metabolomics and network pharmacology can unveil the mechanisms of diseases and drug action.