Dub mulberry (Morus nigra Linn.) yog ib qho ntawm cov nroj tsuag tseem ceeb ntawm Moraceae genus Morus, feem ntau faib hauv Xinjiang. Black mulberry txiv hmab txiv ntoo tuaj yeem siv tau ob qho tib si tshuaj thiab noj tau. Black mulberry yog me ntsis txias nyob rau hauv cov xwm, qab zib thiab qaub nyob rau hauv saj, nkag mus rau lub siab, lub raum, thiab lub plawv meridians, thiab yog ib tug zoo txiv hmab txiv ntoo rau nourishing lub siab, nourishing thiab ntxiv dag zog rau. Nws muaj lub luag haujlwm ntawm kev txhawb nqa lub cev kua thiab quenching nqhis dej, moistening cov hnyuv, nourishing ntshav thiab nourishing yin. Kev noj cov mulberries tsis tu ncua tuaj yeem txhim kho qhov muag pom thiab txo cov tsos mob ntawm qhov muag qaug zog thiab qhuav. Black mulberries yog nplua nuj nyob rau hauv ntau yam active tshuaj, xws li flavonoids, alkaloids, polyphenols, thiab benzofurans. Cov kev tshawb fawb tshuaj niaj hnub no tau pom tias cov mulberry dub muaj cov tshuaj tiv thaiv qog, antioxidant, tiv thaiv kab mob, tiv thaiv kab mob, tiv thaiv hypertensive thiab hypoglycemic teebmeem.
Metabolic reprogramming tuaj yeem txhawb kev loj hlob thiab kev loj hlob ntawm cov qog nqaij hlav cancer. Serine metabolism plays lub luag haujlwm tseem ceeb hauv kev tumorigenesis, thiab kev ua haujlwm ntawm serine synthesis nrawm nrawm redox homeostasis, amino acid thauj, thiab nucleotide synthesis, muab cov qog nqaij hlav cancer nrog ntau lub zog thiab cov metabolites nruab nrab. 3-phosphoglycerate dehydrogenase (PHGDH) yog thawj tus nqi-limiting enzyme rau de novo synthesis ntawm serine, thiab catalyzes cov synthesis ntawm phosphohydroxypyruvate (3-PPyr) los ntawm 3-phosphoglycerate ({{4}) }PG). Cov kev tshawb fawb tau pom tias PHGDH tau qhia ntau yam hauv tib neeg cov qog, xws li melanoma, mob qog noj ntshav, mob qog noj ntshav, thiab mob qog noj ntshav tsis zoo triple. Inhibition ntawm PHGDH txo serine synthesis thiab inhibits qog cell proliferation, migration thiab ntxeem tau. Yog li, PHGDH inhibitors tuaj yeem ua haujlwm zoo rau kev kho mob qog noj ntshav.
Hauv daim ntawv no, cov txiv hmab txiv ntoo ntawm cov mulberry dub tau kawm, thiab 20 lub tebchaw raug cais, suav nrog ob lub tebchaw tshiab, moranigrineA thiab morusamine. Ntawm lawv, MoranigrineA yog ib qho tsis tshua muaj sib xyaw nrog pyrrole-2-aldehyde thiab 2-arylbenzofuran structural units, thiab cov sau phau ntawv speculate nws txoj kev biosynthetic. Tsab xov xwm tau soj ntsuam cov nyhuv inhibitory ntawm tag nrho cov kev sib cais ntawm PHGDH, thiab pom tias methyl caffeate pom muaj qhov cuam tshuam tseem ceeb ntawm PHGDH. Kinetic tsom xam ntawm enzyme inhibition pom tias methyl caffeate yog ib qho tsis sib tw inhibitor txheeb ze rau substrate 3-PG thiab inhibited nyob rau hauv ib tug concentration-dependent yam. MST tsom xam ntxiv tau lees paub qhov ncaj qha cuam tshuam ntawm methyl caffeate nrog PHGDH.
Tsis tas li ntawd, molecular docking qhia tias methyl caffeate khi rau lub hnab tshos allosteric ntawm PHGDH es tsis yog nws qhov chaw nquag, uas zoo ib yam nrog cov ntaub ntawv ntawm enzyme kinetics. Kev sim ntawm tes tau pom tias methyl caffeate tuaj yeem cuam tshuam kev loj hlob ntawm HeLa hlwb; Cov kws sau ntawv tau pom ntxiv tias methyl caffeate tuaj yeem txhawb lub apoptosis ntawm HeLa hlwb thiab ntes lub voj voog ntawm tes. CETSA thiab siRNA kev sim kuj tau ua pov thawj tias methyl caffeate ncaj qha rau PHGDH. Nyob rau tib lub sijhawm, methyl caffeate muaj qhov pom tseeb inhibitory nyhuv ntawm cov qog loj hlob hauv HeLa cell xenograft nas qauv nrog cov tshuaj toxicity tsawg. Cov txiaj ntsig saum toj no qhia tau tias methyl caffeate tuaj yeem siv los ua PHGDH ntuj inhibitor, muab cov ntsiab lus tseem ceeb rau kev tshawb fawb ntawm cov tshuaj tiv thaiv kab mob tsom rau PHGDH, thiab Mnigra tuaj yeem siv los ua zaub mov ua haujlwm rau kev tiv thaiv thiab kho mob qog noj ntshav.
