Spatially resolved metabolomics visualizes heterogeneous distribution of metabolites in lung tissue and the anti-pulmonary fibrosis effect of Prismatomeris connate extract
10.1016/j.jpha.2024.100971
- Author:
Jiang HAIYAN
1
;
Zheng BOWEN
;
Hu GUANG
;
Kuang LIAN
;
Zhou TIANYU
;
Li SIZHENG
;
Chen XINYI
;
Li CHUANGJUN
;
Zhang DONGMING
;
Zhang JINLAN
;
Yang ZENGYAN
;
He JIUMING
;
Jin HONGTAO
Author Information
1. New Drug Safety Evaluation Center,Institute of Materia Medico,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing,100050,China
- Keywords:
Spatially resolved metabolomics;
Mass spectrometry imaging;
Network pharmacology;
Pulmonary fibrosis;
Prismatomeris connate extract
- From:
Journal of Pharmaceutical Analysis
2024;14(9):1330-1346
- CountryChina
- Language:Chinese
-
Abstract:
Pulmonary fibrosis(PF)is a chronic progressive end-stage lung disease.However,the mechanisms un-derlying 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 spec-trometry 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 biosyn-thesis and alanine,asparate and glutamate metabolism,the downregulation of arachidonic acid meta-bolism,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.
