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

Abstract

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.

Peimine Alleviated Bleomycin-Induced Pulmonary Fibrosis in Mice Through Reducing Epithelial-Mesenchymal Transition, Inflammation and Oxidative Stress and Regulating Host Metabolism

“…An in vivo study revealed that the BLM can alter the distribution of metabolites in mice, while terrestrosin D reversed this change by regulating amino acid and lipid metabolism. 15 Baicalin can effectively inhibit the pathological changes of PF caused by BLM. Additionally, baicalin may improve PF by modulating 4 key pathways, including taurine and hypotaurine metabolism, glutathione metabolism, and glycerophospholipid metabolism.…”

Metabolomics and serum pharmacochemistry revealed the preventive mechanism of Gushudan in kidney‐yang‐deficiency‐syndrome rats

“…Metabolomics investigates the dynamic changes of small molecules in living organisms (Yang et al, 2022). It is often used to reveal the mechanism of action of drugs (X. Li et al, 2021).…”

Inhibition of bleomycin‐induced pulmonary fibrosis in SD rats by sea cucumber peptides

“…Network pharmacology can elucidate molecular mechanisms of action of metabolomics by finding relationships between compounds and potential targets. Similarly, metabolomics and network pharmacology revealed that terrestrosin D attenuated bleomycin‐induced PF mice, reversed inflammatory damage in the lung by modulating amino acid and lipid metabolism and identified TNF‐ α and TGF‐ β 1 as therapeutic targets 24 . Therefore, metabolomics and network pharmacology analyses are usually combined for the study of metabolic pathways.…”