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Nyumba yamphamvu pansi pa dziko loletsa kukalamba——NMNH

Nkhani

Nyumba yamphamvu pansi pa dziko loletsa kukalamba——NMNH

2024-08-27 10:00:38


Kuyambira pamene NMN inapezeka ndi gulu la pulofesa wa Harvard David Sinclair ku 2013, NMN yapitirizabe kukhala yotchuka pakati pa anthu odana ndi ukalamba ndipo imadziwika ndi kugwiritsidwa ntchito ndi anthu ambiri. Komabe, mu 2021, gulu la Pulofesa Deng Haiteng waku Tsinghua University adasindikiza nkhani yotchedwa "Reduced Nicotinamide Mononucleotide (NMNH) Potently Enhanced NAD+ and Suppresses Glycolysis, the TCA Cycle, and Cell Growth" mu "Journal of Proteome Research", indic : Monga mtundu watsopano wa NAD + supplement,NMNHali ndi luso loletsa kukalamba mu vivo ndi mu vitro kuposa NMN.

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01 .NMNHkumawonjezera ma cell NAD + ndi NADH. Ofufuza adayerekezera zotsatira za NMN ndi NMNH pakuwonjezera ma cell NAD +. Kuchiza ndi NMNH (100 μM) kumawonjezera ma cell NAD+ ndi 5-fold mu cell HepG2, pomwe 100 μM NMN idangowonjezera milingo ya NAD+ pang'ono. Kuphatikiza pa ma cell a HepG2, ofufuzawo adatsimikiziranso kuti NMNH idakulitsa NAD + m'maselo a ES-2 ndi ma cell a 3T3-L1, omwe ndi maselo opangidwa ndi ovary amunthu ndi ma cell a embryonic fibroblast motsatana. Ndipo ofufuzawo adapezanso kuti NMNH idachulukitsa ma cell NAD + m'maselo a 786-O munthawi yodalira komanso kudalira. Ofufuzawo anayeza NADH pogwiritsa ntchito ma spectrometry ambiri ndipo adapeza kuti milingo ya NADH m'maselo a HepG2 opangidwa ndi NMNH inali nthawi ya 2.5 kuposa ma cell osathandizidwa ndi a NMN, ndipo milingo yapamwamba ya NADH idapezekanso m'maselo a 786-O opangidwa ndi NMNH. Tinapezanso kuti chithandizo cha 340 mg / kg NMNH chinawonjezera kuchuluka kwa NADH mu chiwindi cha mbewa ndi 3-fold, pamene 340 mg / kg NMN chithandizo chinawonjezera ma NADH ndi 1.7-fold.
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Chithunzi 1.2. NMNH imawonjezera milingo ya NAD+

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Chithunzi 3.4. NMNH imawonjezera kuchuluka kwa NMNH

02NMNH imalepheretsa glycolysis ndi TCA kuzungulira. Kuchuluka kwa NADH kumachepetsa glycolysis ndi TCA kuzungulira. Kuti muwone momwe ma cell amayankhira ku chithandizo cha NMNH, ofufuzawo adasanthula metabolomicNMNH-ndi ma cell okhala ndi NMN. Zinapezeka kuti chithandizo cha NMNH sichinangochepetsa milingo ya glycolysis intermediates, komanso kuchepetsa milingo ya TCA cycle intermediates. Zotsatira izi zikuwonetsa kuti kudzikundikira kwa NADH kopangidwa ndi NMNH kumalepheretsa ma cell glycolysis ndi TCA cycle.
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Chithunzi 5. Kuchepetsa glycolysis ndi TCA cycle intermediates

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Chithunzi 6. Kusanthula kwa Metabolomics

03 .NMNHimalepheretsa kukula kwa maselo Ofufuza adafufuza momwe NMNH imakhudzira kukula kwa maselo ndipo adapeza kuti chithandizo cha NMNH chinalepheretsa kukula kwa maselo a HepG2 pazigawo zapamwamba kuposa 250 μM. Ofufuzawo adasanthula ma cell a cell mu ma cell a HepG2 omwe amachitidwa ndi 1 mM NMNH kapena NMN kwa maola 12 ndipo adapeza kuti NMNH idayambitsa kumangidwa kwa cell, pomwe NMN inalibe mphamvu pamayendedwe a cell. Kuonjezera apo, ofufuzawo adapezanso kuti 500 μM NMNH inalepheretsa kukula kwa maselo a 786-O; 250 μM NMNH ikhoza kulepheretsa kukula kwa maselo mu HK-2 maselo.
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Chithunzi 7.8.NMNH imalepheretsa kukula kwa maselo mu vitro

04 .NMNHofufuza zachitetezo adayesa ngati kuchuluka kwa NMNH kumapangitsa hepatotoxicity. Kuchiza mbewa zamphongo za C57BL/6J zokhala ndi 50, 100, 500, kapena 1000 mg/kg NMNH kudzera mu jekeseni wa intraperitoneal tsiku lililonse kwa sabata imodzi sizinawonetse kuchepa kwa serum alanine aminotransferase (ALT) ndi aspartate aminotransferase (AST). Kukwezeka, kusonyeza kuti NMNH si hepatotoxic pa mlingo waukulu. Kuphatikiza apo, ofufuzawo adapezanso kuti chithandizo cha NMNH chidakulitsa zomwe zili mu NAD + m'chiwindi cha mbewa motengera mlingo. Chithandizo cha 1000 mg/kg NMNH chinachulukitsa milingo ya NAD+ m'chiwindi cha mbewa kuposa nthawi za 10.
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Chithunzi 10.NMNHkumawonjezera mulingo wa NAD + pachiwindi cha mbewa

Kafukufuku wasonyeza kuti NMNH ndi yabwino NAD+ -boosting supplement kuposa NMN onse mu vitro ndi mu vivo; Kuphatikiza apo, NMNH imachulukitsa kuchuluka kwa NAD (NADH) m'maselo ndi ziwindi za mbewa. Kusanthula kwa Metabolomic kunawonetsa kuti NMNH imaletsa glycolysis ndi TCA kuzungulira. Kuyesa kwa in vitro kukuwonetsa kuti NMNH imathandizira kumangidwa kwa ma cell ndikuletsa kukula kwa maselo. Kuphatikizidwa pamodzi, kafukufukuyu akuwonetsa kuti NMNH ndiyowonjezera NAD+ yowonjezera ndipo imalepheretsa glycolysis, TCA cycle, ndi kukula kwa maselo.

Dzina lachi China la NMNH ndi "kuchepetsedwa β-nicotinamide mononucleotide", yomwe ndi mawonekedwe ochepetsedwa a NMN ndipo ndi amorphous yellow powder. Mapangidwe a maselo: C11H17N2O8P Kulemera kwa maselo: 336.23g/molCAS Na.: 108347-85-9 Zolemba zaposachedwa za kafukufuku zikuwonetsa kuti NMNH imawonjezera milingo ya NAD+ mwachangu komanso pamlingo wapamwamba kwambiri, pafupifupi nthawi za 5 kuposa za NMN
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