Part 2: Acteoside Repressed Microglia M1 Polarization Los Ntawm Inhibited NF-κB Kev Qhia Txog Txoj Kev Thiab AMPK-Mediated Mitochondria Function Recovery

Hu rau: Audrey Hu Whatsapp / hp: 0086 13880143964 Email:audrey.hu@wecistanche.com

Pls nyem qhov no mus rau Part 1

AD (Alzheimer tus kab mob) yog cov kab mob neuronal thiab kev paub tsis meej, nrog cov txheej txheem nyuaj dysregulated [17]. Cov ntaub ntawv pov thawj tau ua pov thawj pom tias muaj kev cuam tshuam tsis zoo ntawm microglia-tsav in§ammation hauv hlwb. Nws zoo nkaus li ua lub luag haujlwm tseem ceeb hauv kev nce qib ntawm AD(Alzheimer tus kab mob). Microglia yog macrophages hauv hlwb [18]. Nws tuaj yeem qhib tau rau ib qho classical M1 in§ammatory phenotype, tus cwj pwm los ntawm kev txhim kho zais cia ntawm proin§ammatory cytokines[4]. Kev ua kom M1 ntau dhau tuaj yeem ua rau muaj kev puas tsuaj rau neuron thiab neurodegeneration, txawm tias ua rau AD(Alzheimer tus kab mob) [19]. Yog li, nws yog ib qho tseem ceeb los nrhiav cov kev kho mob tshiab uas tswj xyuas cov ntsiab lus microglia polarization uas tuaj yeem muab cov txiaj ntsig zoo.

Peb txoj haujlwm dhau los tau lees paub tias ACT(acteoside los ntawm cistanche)muaj qhov cuam tshuam tsis zoo ntawm kev txhim kho kev kawm thiab kev nco muaj peev xwm thiab tiv thaiv cov neurons hauv nas [20]. Tsis tas li ntawd, txoj kev tshawb fawb tam sim no kuj tau ua pov thawj tias ACT tuaj yeem txo qis AlCl3-induced dyskinesia thiab cholinergic system disorder hauv zebra¦sh. Zoo siab heev, ACT(acteoside los ntawm cistanche)nthuav tawm cov kev ua ub no zoo kawg nkaus los tiv thaiv kev ua phem hauv LPS-induced BV-2 hlwb. Lub transcriptomic pro ¦le ¦ tau lees paub qhov cim tsis tuaj yeem hloov pauv hauv LPS-induced cells piv nrog cov hlwb tswj, nrog rau ACT-kho cov hlwb piv nrog LPS-induced.

ACT(acteoside los ntawm cistanche) suppressed M1 polarization los ntawm inhibiting NK-κB txoj kev. Tsuas yog txoj hauv kev NF-κB, RNA-seq kuj pom tias ACT(acteoside los ntawm cistanche)Kev kho mob tuaj yeem cuam tshuam arginine biosynthesis nrog rau pantothenate thiab CoA biosynthesis. Interestingly, ob txoj kev metabolic tau txuas ntxiv los ntawm HPLC-Q-TOF-MS tsom xam. Nws tau tshaj tawm tias iNOS tuaj yeem ua rau Arg tsis muaj thiab citrulline thaum Arg -1 tuaj yeem hydrolyze Arg rau ornithine thiab urea, cuam tshuam nrog kho neuron[21]. LPS stimulation coj mus rau upregulation ntawm iNOS (Fig. 3a) thiab downregulation ntawm Arg-1 (Fig. 3b), uas ua rau nce NO theem (Fig. 2f). Cov ntaub ntawv tau nthuav tawm tias ACT(acteoside los ntawm cistanche)alleviated nce qib NO los ntawm arginine biosynthesis.

Pantothenic acid (PA) yog thawj substrate rau pantothenate kinase [22], raws li tus nqi-txheej metabolite hauv CoA biosynthesis. PA yog lub luag haujlwm ua ntej ntawm acetyl-CoA, uas yog qhov tseem ceeb tshwj xeeb rau cholinergic neurons[23] thiab koom nrog lub voj voog tricarboxylic acid (TCA voj voog) [24]. Ib txoj kev tshawb fawb tsis ntev los no tau qhia tias kev nce siab ntawm CoA yuav ua rau hloov pauv mitochondrial morphology, thiab cov ntsiab lus ATP qis dua [22]. LPS-induced BV-2 hlwb tau pom qhov txo qis ntawm cov mitochondria thiab hloov pauv ntawm mitochondrial zoo li qub. Tom qab raug ntxias los ntawm LPS, qhov tsim ntawm ROS tau nce hauv BV-2 hlwb. Tom qab ntawd lub overladen ROS ua rau daim nyias nyias phospholipid raug tawm tsam los ntawm dawb radical[25]. Nws ua rau poob ntawm MMP, nyob rau hauv lem, mitochondrial dysfunction thiab ATP depletion. Nws yog qhov zoo tshaj plaws uas ACT(acteoside los ntawm cistanche)Kev kho mob tau txo qis ntawm MMP thiab ATP cov ntsiab lus. Cov ntaub ntawv no qhia tias ACT(acteoside los ntawm cistanche)induced mitochondrial dysfunction los ntawm kev tswj pantothenate thiab CoA biosynthesis.

Nws tau raug nthuav qhia tias microglia polarization yog ze rau cov metabolism hauv cell[14]. Tshwj xeeb, raws li lub hub metabolic, mitochondria plays lub luag hauj lwm zoo kawg li hauv regulating cell metabolism. Tsis ntev los no, mitochondria tau muab tso rau hauv qhov kev txiav txim tseem ceeb hauv microglia polarization[26]. Txhawm rau kom nkag siab zoo dua cov txheej txheem ntawm ACT(acteoside los ntawm cistanche), peb txiav txim siab lub luag haujlwm ntawm mitochondria los ntawm kev tsom xam western blot. Nws qhia tias ACT(acteoside los ntawm cistanche)induced mitochondrial dysfunction los ntawm kev ua kom lub AMPK /PGC- 1/UCP-2 axis.

PGC-1 thiab UCP-2 yog ob qho tib si ntsig txog mitochondrial biogenesis[27, 28], thiab lawv tuaj yeem xav tias yog tus tswj hwm tus tswv ntawm ROS[29]. Cov ntawv ceeb toom qhia tias PGC-1 -kev kho mitochondrial biogenesis thiab kev txo qis ntawm ROS yog nyob ntawm qhov induction ntawm UCP-2[27–29]. Vim yog overloading ROS, qhov kev qhia ntawm PGC-1 thiab UCP{10}} tau down-regulated nyob rau hauv LPS-induced BV{13}} hlwb. Nws qhia tias ACT(acteoside los ntawm cistanche)tuaj yeem tshem tawm ROS ntau dhau los ntawm PGC-1 thiab UCP-2, yog li rov ua haujlwm mitochondrial. Raws li cov ntaub ntawv, kev hloov pauv ntawm PGC-1 hauv BV-2 hlwb tuaj yeem ua rau muaj kev tswj hwm polarization. Interestingly, ib daim ntawv tshaj tawm yav dhau los tau pom tias nce PGC-1 qhia tawm inhibit NF-κB kev ua hauv LPS-induced BV-2 hlwb[30]. Nws ua tau zoo txog kev sib raug zoo ntawm PGC-1 thiab NF-κB hauv peb txoj kev kawm.

Qhov kev qhia ntawm PGC-1 yog cuam tshuam los ntawm cov dej ntws mus rau cov protein, xws li AMPK. AMPK yog cov protein tseem ceeb rau kev saib xyuas ntawm cellular homeostasis[31], ua si ntau lub luag haujlwm hauv kev txhawb nqa M2 polarization ntawm microglia[32]. Nws hloov kho cov txheej txheem metabolic hauv cov hlwb [33]. Peb pom tias ACT(acteoside los ntawm cistanche)txhawb kev ua kom AMPK. Nyob rau tib lub sijhawm, daim ntawv thov ntawm compound C (AMPK inhibitor) thaiv cov nyhuv ntawm ACT ntawm attenuating LPS-induced NO tshaj. Yog li, ACT kuj tseem txwv tsis pub LPS-stimulated M1 polarization ntawm AMPK txoj kev taw qhia.

Nws yog lub sijhawm thawj zaug los tshaj tawm cov txheej txheem ntawm ACT(acteoside los ntawm cistanche)ntawm regulating microglia polarization (Fig. 10). Cov ntaub ntawv txhawb nqa tias ACT tuaj yeem tsim los ua tus neeg sawv cev kho mob rau cov kab mob neurodegenerative cuam tshuam nrog neuroin§ammation, xws li AD(Alzheimer tus kab mob) . Tshwj xeeb, peb txuas microglia polarization rau cell metabolism, piav qhia txog cov txiaj ntsig ntawm ACT(acteoside los ntawm cistanche)los ntawm kev hloov pauv ntawm mitochondria muaj nuj nqi. Qhov kev txheeb xyuas qhov tseeb ntawm qhov metabolic axis, lub hom phiaj ntawm qhov no yog ib qho chaw tshwj xeeb, tuaj yeem tso cai rau kev kho kom zoo dua ntawm microglia M1 polarization, tshwj xeeb hauv AD(Alzheimer tus kab mob) .