Abstract
This study aimed to evaluate whether ginsenosides Rb1 (20-S-protopanaxadiol aglycon) and Rg1 (20-S-protopanaxatriol aglycon) have mitochondrial protective effects against oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in primary mouse astrocytes and to explore the mechanisms involved. The OGD/R model was used to mimic the pathological process of cerebral ischemia-reperfusion in vitro. Astrocytes were treated with normal conditions, OGD/R, OGD/R plus Rb1, or OGD/R plus Rg1. Cell viability was measured to evaluate the cytotoxicity of Rb1 and Rg1. Intracellular reactive oxygen species (ROS) and catalase (CAT) were detected to evaluate oxidative stress. The mitochondrial DNA (mtDNA) copy number and mitochondrial membrane potential (MMP) were measured to evaluate mitochondrial function. The activities of the mitochondrial respiratory chain (MRC) complexes I–V and the level of cellular adenosine triphosphate (ATP) were measured to evaluate oxidative phosphorylation (OXPHOS) levels. Cell viability was significantly decreased in the OGD/R group compared to the control group. Rb1 or Rg1 administration significantly increased cell viability. Moreover, OGD/R caused a significant increase in ROS formation and, subsequently, it decreased the activity of CAT and the mtDNA copy number. At the same time, treatment with OGD/R depolarized the MMP in the astrocytes. Rb1 or Rg1 administration reduced ROS production, increased CAT activity, elevated the mtDNA content, and attenuated the MMP depolarization. In addition, Rb1 or Rg1 administration increased the activities of complexes I, II, III, and V and elevated the level of ATP, compared to those in the OGD/R groups. Rb1 and Rg1 have different chemical structures, but exert similar protective effects against astrocyte damage induced by OGD/R. The mechanism may be related to improved efficiency of mitochondrial oxidative phosphorylation and the reduction in ROS production in cultured astrocytes.
Highlights
Ischemic stroke is one of the leading causes of adult disability in the world
Our results revealed that intracellular reactive oxygen species (ROS) were significantly increased and that CAT activity was markedly reduced when astrocytes were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) conditions
It is necessary to conduct further investigations aimed at the effects of Rb1 and Rg1 in the regulation of mitochondria function and their associated signaling pathway in neurons and astrocytes cocultured under OGD/R-induced damage by measuring experimental indexes including oxidative phosphorylation (OXPHOS), mitochondrial function, cell redox state, and STAT3 relevant signaling pathway
Summary
Ischemic stroke is one of the leading causes of adult disability in the world. Astrocytes are the most abundant cell type in the central nervous system (CNS) and serve supportive and nutritive roles for neurons. Astrocytes perform several functions that are essential for the formation and maintenance of the blood–brain barrier (BBB), the regulation of brain water and ion homeostasis, and presumably many. Ginsenosides are the primPaarnyaxacgtiinvseencgomCp.Ao.nMenetsyeorfisthaiscohmermb,oannlyd uhsaevdeCahivnaersieetymeodf ipcihnaarlmhaecrobl.oGgiicnasleneoffseicdtes,s saurechthaes parnimtioaxriydaanctt,ivaenctio-minpfloamnemntastoorfy,thaisnthiaeprbop, taontdic haanvde naevuarroipetryoteocftipvhearpmroapcoerlotigeisc.aGl einffseecntso,sisduecsh aarse adnetriiovxaitdivanest,oafnttrii-tienrflpaenmomidatdoarmy,maanrtaianpeo, pwthoticich acnodnsnisetsuroofptrhoitretycticvaerbpornopateormtiess..ThGeiynsceannobseidmesaianrley dcelarsivsiaftieivdesinotof tprirtoetroppeannoaixdaddaioml m(PaDra) naen,dwphriocthopcoannasixsattsroioflt(hPiTrt)ygcianrsbeonnosaidtoems,sb. AAnniinnccrreeaassiinngg aammoouunntt ooff eevviiddeennccee hhaass iinnddiiccaatteedd tthhaatt RRbb aanndd RRgg eexxeerrtt nneeuurroopprrootteeccttiivvee eeffffeeccttss bbootthhiinnvviivvooaannddiinnvviittrroo[[77––1111]]. IItt hhaass bbeeeenn ffoouunndd tthhaatt RRbb aanndd RRgg iimmpprroovveemmiittoocchhoonnddrriiaallffuunnccttiioonn aannddreregguulaltaetethtehelevleevl eolf oAfTAP TtoPptrootpecrtonteecrtvenecrevlles acgeallisnsatgcaeirnesbtracel risecbhreaml iisac-hreepmeriafu-rseiopnerifnujusiroyn[1in2,j1u3r]y. W[1h2e,1t3h]e.rWRbh1etahnedr RRgb haanvde Rangy ehffaevcetsaonnymefitfoeccthsoonndrmiailtfoucnhcotniodnriuanl dfuerncotxioyngeunn–dgleurcooxseygdeenp–rgivluatcioosne (dOeGpDri)vaantidonre(oOxGygDe)naantidonre(OoxGyDg/eRn)actioonnd(itOioGnDs /inR)asctornodcyittieosniss isntilalsutnrokcnyotwesni.sWsthileltuhnerknthoewsent.wWohteytpheesr othf esasepotwnionstyshpoews osfimsailpaornitiiness asnhdo/worsdimiffielarerintcieess ainndp/hoarrmdiaffceorleongcyesunindeprhOarGmDa/cRolcoognydiutinodnesrreOmGaDin/Rs ucnocnldeiatri.onHsernecme,aiinnsthuenpclreeasre.nHt setnucdey, ,inwtehienvperestsiegnattesdtutdhye, ewffeecintsvoefstRigba1teadndthRege1ffoenctsOoGfDR/bR1-ianndducRegd ionnjurOyGaDnd/Rf-uinrtdhuecreedxpinlojureryd tahnedufnudrethrleyrinegxpmloorleedcutlhaer munecdhearlnyiisnmg imn oplreimcualaryr cmueltcuhraendisamstrioncyptreism. W[1h2e,1t3h]e.rWRbh1etahnedr RRgb haanvde Rangy ehffaevcetsaonnymefitfoeccthsoonndrmiailtfoucnhcotniodnriuanl dfuerncotxioyngeunn–dgleurcooxseygdeenp–rgivluatcioosne (dOeGpDri)vaantidonre(oOxGygDe)naantidonre(OoxGyDg/eRn)actioonnd(itOioGnDs /inR)asctornodcyittieosniss isntilalsutnrokcnyotwesni.sWsthileltuhnerknthoewsent.wWohteytpheesr othf esasepotwnionstyshpoews osfimsailpaornitiiness asnhdo/worsdimiffielarerintcieess ainndp/hoarrmdiaffceorleongcyesunindeprhOarGmDa/cRolcoognydiutinodnesrreOmGaDin/Rs ucnocnldeiatri.onHsernecme,aiinnsthuenpclreeasre.nHt setnucdey, ,inwtehienvperestsiegnattesdtutdhye, ewffeecintsvoefstRigba1teadndthRege1ffoenctsOoGfDR/bR1-ianndducRegd ionnjurOyGaDnd/Rf-uinrtdhuecreedxpinlojureryd tahnedufnudrethrleyrinegxpmloorleedcutlhaer munecdhearlnyiisnmg imn oplreimcualaryr cmueltcuhraendisamstrioncyptreism. ary cultured astrocytes
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