01.
I-NMNHinyusa amazinga e-NAD+ kanye ne-NADH yeselula. Abacwaningi baqhathanise imiphumela ye-NMN ne-NMNH ekwandiseni amazinga e-NAD+ yamaselula. Ukwelashwa nge-NMNH (100 μM) kukhuphule amazinga e-NAD+ yeselula ngo-5-fold kumaseli e-HepG2, kanti i-100 μM NMN inyuse kancane amazinga e-NAD+. Ngaphezu kwamaseli e-HepG2, abacwaningi baphinde baqinisekisa ukuthi i-NMNH ithuthukise i-NAD+ kumaseli e-ES-2 kanye namaseli e-3T3-L1, okungamaseli asuselwa ku-ovary yomuntu kanye namaseli asuselwa ku-embryonic fibroblast, ngokulandelana. Futhi abacwaningi baphinde bathola ukuthi i-NMNH inyuse amazinga e-NAD+ yamaselula kumaseli we-786-O ngendlela encike esikhathini nangendlela yokuhlushwa. Abacwaningi balinganise i-NADH besebenzisa i-mass spectrometry futhi bathola ukuthi amazinga e-NADH kumaseli e-HepG2 alashwe yi-NMNH ayephakeme izikhathi ezingu-2.5 kunamaseli angalashwanga nalashwa nge-NMN, futhi amazinga e-NADH aphakeme nawo atholwa kumaseli angu-786-O alashwe yi-NMNH. Siphinde sathola ukuthi ukwelashwa kwe-NMNH okungu-340 mg/kg kukhuphule amazinga e-NADH ezisibindini zegundane ngokuphindwe izikhathi ezingu-3, kuyilapho ukwelashwa kwe-NMN okungu-340 mg/kg kukhuphule amazinga e-NADH ngo-1.7-fold.
Umfanekiso 1.2. I-NMNH inyusa amazinga e-NAD+
Umfanekiso 3.4. I-NMNH inyusa amazinga e-NMNH
I-02NMNH ivimbela i-glycolysis kanye nomjikelezo we-TCA. Ukuqoqwa kwe-NADH kwehlisa i-glycolysis kanye nomjikelezo we-TCA. Ukuhlola impendulo ye-metabolic yamaseli ekwelapheni kwe-NMNH, abacwaningi benza ukuhlaziywa kwe-metabolomic
NMNH-kanye namaseli aphethwe yi-NMN. Kutholakale ukuthi ukwelashwa kwe-NMNH akugcini nje ukunciphisa amazinga e-glycolysis intermediates, kodwa futhi kunciphise amazinga we-TCA cycle intermediates. Le miphumela ibonisa ukuthi ukuqoqwa kwe-NADH okukhiqizwa yi-NMNH kuvimbela i-glycolysis yeselula kanye nomjikelezo we-TCA.
Umfanekiso 5. Ukunciphisa i-glycolysis kanye ne-TCA yomjikelezo ophakathi
Umfanekiso 6. Ukuhlaziywa kwe-Metabolomics
03.
I-NMNHkuvimbela ukukhula kwamangqamuzana Abacwaningi bahlole umphumela we-NMNH ekukhuleni kwamaseli futhi bathola ukuthi ukwelashwa kwe-NMNH kuvimbela ukukhula kwamaseli e-HepG2 ekugxilweni okuphezulu kune-250 μM. Abacwaningi bahlaziye umjikelezo weseli kumaseli we-HepG2 aphathwe nge-1 mM NMNH noma i-NMN amahora angu-12 futhi bathola ukuthi i-NMNH ibangele ukuboshwa komjikelezo weseli, kuyilapho i-NMN ingenawo umthelela kumjikelezo weseli. Ngaphezu kwalokho, abacwaningi bathola nokuthi i-500 μM NMNH ivimbele ngokuphelele ukukhula kwamaseli we-786-O; 250 μM NMNH ingavimbela ngempumelelo ukukhula kwamaseli kumaseli e-HK-2.
Umfanekiso 7.8.NMNH uvimbela ukukhula kwamaseli ku-vitro
04.
I-NMNHabacwaningi bezokuphepha benze izivivinyo zokuthi imithamo ephezulu ye-NMNH idala i-hepatotoxicity. Ukwelashwa kwamagundane abesilisa e-C57BL/6J ane-50, 100, 500, noma i-1000 mg/kg NMNH ngomjovo we-intraperitoneal njalo ngemva kwesonto elilodwa akuvezanga ukuncipha kwe-serum alanine aminotransferase (ALT) namazinga e-aspartate aminotransferase (AST). Iphakanyisiwe, okubonisa ukuthi i-NMNH ayiyona i-hepatotoxic kumithamo ephezulu. Ngaphezu kwalokho, abacwaningi baphinde bathola ukuthi ukwelashwa kwe-NMNH kwenyusa okuqukethwe kwe-NAD+ kusibindi samagundane ngendlela encike kumthamo. Ukwelashwa nge-1000 mg/kg NMNH kwenyuse amazinga e-NAD+ esibindini samagundane izikhathi ezingaphezu kweziyi-10.
Umfanekiso 10.
I-NMNHinyusa izinga le-NAD+ esibindini samagundane
Ucwaningo luye lwabonisa ukuthi i-NMNH iyisengezo esingcono se-NAD+-sokukhuthaza kune-NMN kokubili ku-vitro kanye ne-vivo; ngaphezu kwalokho, i-NMNH inyusa amazinga e-NAD (NADH) ancishisiwe kumaseli nesibindi segundane. Ukuhlaziywa kwe-metabolomic kubonise ukuthi i-NMNH ivimbela i-glycolysis kanye nomjikelezo we-TCA. Ukuhlolwa kwe-in vitro kubonisa ukuthi i-NMNH idala ukuboshwa komjikelezo weseli futhi ivimbele ukukhula kwamaseli. Sekuhlanganiswe ndawonye, lolu cwaningo lubonisa ukuthi i-NMNH iyisithuthukisi se-NAD+ esinamandla futhi ivimbela i-glycolysis, umjikelezo we-TCA, nokukhula kwamaseli.
Igama lesiShayina le-NMNH "lincishisiwe i-β-nicotinamide mononucleotide", okuyindlela encishisiwe ye-NMN futhi iyimpuphu ephuzi e-amorphous. Ifomula ye-molecular: C11H17N2O8P Isisindo se-molecular: 336.23g/molCAS No.: 108347-85-9 Izincwadi zocwaningo zakamuva zibonisa ukuthi i-NMNH inyusa amazinga e-NAD+ ngokushesha nangokugxila okuphezulu, ngokwesilinganiso izikhathi ezingu-5 kune-NMN
Indlela yezempiloI-NMNHisibhamu sangempela
