Molecular Mechanism of Anti-neuroinflammation effect of Notoginsenside R1 Based on Plasma Metabolomics
Objective:This study applied plasma metabolomics to analyze the mechanism of notoginsenside R1(NGR1)against neuroinflammation.Methods:The neuroinflammation model was constructed by intraperitoneal injection of lipopolysaccharide(LPS,0.83 mg‧kg-1),and NGR1(30 mg‧kg-1)was used for treatment.Blood was collected from the orbital venous plexus of mice,and plasma was isolated.Hematoxylin-Eosin(HE)staining was employed for detecting the damage to the brain tissue of mice,and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was employed to detect neuroinflammation-related indicators.Enzyme-linked immunosorbent reaction(ELISA)was used to analyze the changes in inflammatory factors.Metabolomics analysis of mouse plasma samples was performed by liquid chromatography-mass spectrometry(LC-MS),and differential endogenous metabolites were identified by Human Metabolome Database(HMDB)and Kyoto Encyclopedia of Genes and Genomes(KEGG).MetaboAnalyst and Metscape databases were used to further analyze the key metabolic pathways of differential endogenous metabolites.Finally,qRT-PCR was used to detect the changes in gene expression levels regulating key metabolic pathways.Results:The experiments showed that NGR1 could significantly improve nerve injury in the brain tissue of mice and significantly reduce the mRNA levels of central nervous inflammatory factor calcium-ionized binding adaptation molecule 1(Iba-1),interleukin-1β(IL-1β),and IL-6.It could significantly increase the mRNA level of transforming growth factor-β(TGF-β)and decrease the expression levels of serum inflammatory factors IL-6 and TNF-α.Furthermore,metabolomics results revealed that 22 different endogenous metabolites such as corticosterone,indole-3-pyruvic acid,D-(+)-pantothenic acid,12S-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid,and PC(18:3(9Z,12Z,15Z)/16:1(9Z))in plasma of mice were significantly changed between the model group and the administration group.They were mainly involved in glycerophospholipid metabolism,linoleic acid metabolism,and steroid hormone biosynthesis.The results of qRT-PCR showed that the mRNA expression levels of PLA2G2A,PLA2G1B,PLA2G12A,AKR1D1,HSD11B1,and HSD11B2 in the key metabolic pathways were significantly reversed after administration.Conclusion:This study suggests that NGR1 has a therapeutic effect on LPS-induced neuroinflammation and may act as an anti-neuroinflammatory agent by regulating key metabolites such as corticosterone and key pathways such as glycerophospholipid metabolism,linoleic acid metabolism,and steroid hormone biosynthesis,which will provide a basis for in-depth research on the mechanism of NGR1 against anti-neuroinflammation.
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