Protective effect of isosteviol sodium against LPS-induced multiple organ injury by regulating of glycerophospholipid metabolism and reducing macrophage-driven inflammation. (October 2021)

• Record Type: Journal Article
• Authors: Wang, Shanping; Tan, Keai Sinn; Beng, Huimin; Liu, Fei; Huang, Jiandong; Kuai, Yihe; Zhang, Rui; Tan, Wen
• Is Part Of: Pharmacological research. Volume 172(2021)
• Publication Date: 2021-10
• Subjects: Isosteviol sodium (PubChem CID 99514) -- Lipopolysaccharide (PubChem CID 11970143) -- Dexamethasone (PubChem CID 5743); STV-Na isosteviol sodium -- LPS lipopolysaccharide -- Dex dexamethasone -- i.p intraperitoneal -- ELISA enzyme-linked immunosorbent assay -- LDH lactic dehydrogenase -- CK creatine kinase -- ALT alanine aminotransferase -- AST aspartate transaminase -- BUN blood urea nitrogen -- Crea creatinine -- UHPLC-TIMS TOF MS/MS ultra-high performance liquid chromatography-trapped ion mobility spectrometry time-of-flight tandem mass spectrometry -- MOI multiple organ injury -- IL-1β interleukin-1β -- IL-6 interleukin-6 -- TNF-α tumor necrosis factor α -- MODS multiple organ dysfunction syndrome -- SIRS systemic inflammatory response syndrome -- LV left ventricular -- FS fractional shortening -- EF ejection fraction -- SV stroke volume -- CO cardiac output -- BW body weight -- HE hematoxylin and eosin -- MTBE methyl tert-butyl ether -- QC quality control -- ESI electrospray ionization -- VIP variable importance in projection -- FD fold change -- TR retention time -- PCA principal components analysis -- PLS-DA partial least squares discrimination analysis -- OPLS-DA orthogonal partial least squares discriminant analysis -- SD standard deviation -- WBC white blood cell -- NEUT neutrophil -- LYMPH lymphocyte -- MONO monocyte -- RBC red blood cell -- PLT Platelet -- HGB hemoglobin -- HCT hematocrit -- MPV mean platelet volume -- MCH mean corpuscular hemoglobin -- BASO basophilicgranulocyte -- EO eosinophilia -- MCHC mean corpuscular hemoglobin concentrate -- PC phosphatidylcholine -- PE phosphatidylethanolamine -- PA phosphatidic acid -- PI phosphatidylinositol -- LysoPC lyso-phosphatidylcholine -- LysoPE lyso-phosphatidylethanolamine -- LysoPA lyso-phosphatidic acid -- LysoPI lyso-phosphatidylinositol -- TLR4 toll-like receptor 4 -- dUDP deoxyuridine diphosphate; Sepsis -- Isosteviol sodium -- Multiple organ injury -- Metabolomics -- Macrophage polarization; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105781
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Sepsis is a severe inflammatory disorder that can lead to multiple organ injury. Isosteviol sodium (STV-Na) is a terpenoid derived from stevioside that exerts anti-inflammatory, antioxidant and antiapoptotic activities. However, the influence of STV-Na on sepsis remains unknown. Here, we assessed the potential effects of STV-Na on sepsis and multiple organ injury induced by lipopolysaccharide (LPS). We found that STV-Na increased the survival rate of mice treat with LPS, significantly improved the functions of the heart, lung, liver, and kidney, reduced the production of inflammatory cytokines and decreased macrophage infiltration. Moreover, Multiorgan metabolomics analysis demonstrated that glutathione metabolism, purine metabolism, glycerophospholipid metabolism and pantothenate and CoA biosynthesis, were significantly altered by STV-Na. This study provides novel insights into the metabolite changes of multiple organ injury in septic mice, which may help characterize the underlying mechanism and provide an improved understanding of the therapeutic effects of STV-Na on sepsis. Graphical Abstract: ga1