Spatially resolved metabolomics visualizes heterogeneous distribution of metabolites in lung tissue and the anti-pulmonary fibrosis effect of Prismatomeris connate extract  

作　　者：Haiyan Jiang Bowen Zheng Guang Hu Lian Kuang Tianyu Zhou Sizheng Li Xinyi Chen Chuangjun Li Dongming Zhang Jinlan Zhang Zengyan Yang Jiuming He Hongtao Jin 

机构地区：[1]New Drug Safety Evaluation Center,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China [2]State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing,100050,China [3]School of Biomedical Sciences,Hunan University,Changsha,410082,China [4]College of Pharmacy,Shaanxi University of Traditional Chinese Medicine,Xianyang,Shaanxi,712046,China [5]Guangxi International Zhuang Medicine Hospital,Nanning,530201,China [6]Key Laboratory for Safety Research and Evaluation of Innovative Drug,National Medical Products Administration,Beijing,102206,China [7]Beijing Union-Genius Pharmaceutical Technology Development Co.,Ltd.,Beijing,100176,China

出　　处：《Journal of Pharmaceutical Analysis》2024年第9期1330-1346,共17页药物分析学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant No.:82074104);the Research Project of Clinical Toxicology Transformation from the Chinese Society of Toxicology,China(Grant No.:CST2021CT101);the Chinese Academy of Medical Science Innovation Fund for Medical Sciences,China(Grant Nos.:2017-I2M-1-011 and 2022-I2M-2-002).

摘　　要：Pulmonary fibrosis (PF) is a chronic progressive end-stage lung disease. However, the mechanisms underlying the progression of this disease remain elusive. Presently, clinically employed drugs are scarce for the treatment of PF. Hence, there is an urgent need for developing novel drugs to address such diseases. Our study found for the first time that a natural source of Prismatomeris connata Y. Z. Ruan (Huang Gen, HG) ethyl acetate extract (HG-2) had a significant anti-PF effect by inhibiting the expression of the transforming growth factor beta 1/suppressor of mothers against decapentaplegic (TGF-β1/Smad) pathway. Network pharmacological analysis suggested that HG-2 had effects on tyrosine kinase phosphorylation, cellular response to reactive oxygen species, and extracellular matrix (ECM) disassembly. Moreover, mass spectrometry imaging (MSI) was used to visualize the heterogeneous distribution of endogenous metabolites in lung tissue and reveal the anti-PF metabolic mechanism of HG-2, which was related to arginine biosynthesis and alanine, asparate and glutamate metabolism, the downregulation of arachidonic acid metabolism, and the upregulation of glycerophospholipid metabolism. In conclusion, we elaborated on the relationship between metabolite distribution and the progression of PF, constructed the regulatory metabolic network of HG-2, and discovered the multi-target therapeutic effect of HG-2, which might be conducive to the development of new drugs for PF.

关 键 词：Spatially resolved metabolomics Mass spectrometry imaging Network pharmacology Pulmonary fibrosis Prismatomeris connate extract 

分 类 号：R563[医药卫生—呼吸系统]