Stevia rebaudiana(Bertoni)Bertoni is a plant known for its natural sweeteners and potential health benefits.Traditionally used to treat diabetes,its impact on cellular signaling proteins such as PKC is unknown.This st...Stevia rebaudiana(Bertoni)Bertoni is a plant known for its natural sweeteners and potential health benefits.Traditionally used to treat diabetes,its impact on cellular signaling proteins such as PKC is unknown.This study begins with examining a database to analyse publications related to S.rebaudiana.The objective was to identify its experimentally validated phytochemicals and biological targets and to perform network pharmacological analysis of gene-disease associations.The identified targets are subsequently validated using a mouse model for LPS-induced PKC phosphorylation assay on mouse macrophage cells.The effect of HPTLC-standardized S.rebaudiana extract was also evaluated using FACS,ELISA,and fluorescence microscopical analysis.A total of 32 unique phytochemicals were found to interact with three targeted proteins,including 5′-Adenosine Monophosphate(AMP)-activated protein kinase catalytic subunit alpha-2/beta-1/gamma-1,1,3-beta-D-glucan synthase,and xanthine dehydrogenase/oxidase.Network analysis and molecular modelling also supported tar-geted lead’s binding and inhibition with AMP-activated protein kinase.The LPS significantly enhanced the phosphorylation of PKC in both ex vivo and in vivo assays.The standardised extract,which contains Rebaudioside and Stevioside at 4.82%w/w and 20.12%w/w,respectively,attenuated the phosphorylation of PKC,suppressed nitric oxide(NO)and reactive oxygen species(ROS).This study found that stevia extract inhibited PKC phos-phorylation in macrophages induced by LPS.Additional research is necessary to understand the potential effects of S.rebaudiana in managing PKC-mediated disorders.This includes exploring the mechanisms by which S.rebaudiana may interact with PKC and the possible therapeutic implications for various health conditions associated with PKC dysregulation.展开更多
文摘Stevia rebaudiana(Bertoni)Bertoni is a plant known for its natural sweeteners and potential health benefits.Traditionally used to treat diabetes,its impact on cellular signaling proteins such as PKC is unknown.This study begins with examining a database to analyse publications related to S.rebaudiana.The objective was to identify its experimentally validated phytochemicals and biological targets and to perform network pharmacological analysis of gene-disease associations.The identified targets are subsequently validated using a mouse model for LPS-induced PKC phosphorylation assay on mouse macrophage cells.The effect of HPTLC-standardized S.rebaudiana extract was also evaluated using FACS,ELISA,and fluorescence microscopical analysis.A total of 32 unique phytochemicals were found to interact with three targeted proteins,including 5′-Adenosine Monophosphate(AMP)-activated protein kinase catalytic subunit alpha-2/beta-1/gamma-1,1,3-beta-D-glucan synthase,and xanthine dehydrogenase/oxidase.Network analysis and molecular modelling also supported tar-geted lead’s binding and inhibition with AMP-activated protein kinase.The LPS significantly enhanced the phosphorylation of PKC in both ex vivo and in vivo assays.The standardised extract,which contains Rebaudioside and Stevioside at 4.82%w/w and 20.12%w/w,respectively,attenuated the phosphorylation of PKC,suppressed nitric oxide(NO)and reactive oxygen species(ROS).This study found that stevia extract inhibited PKC phos-phorylation in macrophages induced by LPS.Additional research is necessary to understand the potential effects of S.rebaudiana in managing PKC-mediated disorders.This includes exploring the mechanisms by which S.rebaudiana may interact with PKC and the possible therapeutic implications for various health conditions associated with PKC dysregulation.