I-mulberry emnyama (i-Morus nigra Linn.) ingenye yezitshalo zokwelapha ezibalulekile zohlobo lwe-Moraceae i-Morus, esakazwa kakhulu e-Xinjiang. Isithelo sikamalibhele omnyama singasetshenziswa kokubili ekwelapheni nasekudleni. I-mulberry emnyama ibanda kancane ngokwemvelo, imnandi futhi imuncu ngokunambitha, ingena esibindini, ezinso, nase-heart meridians, futhi iyisithelo esihle sokondla ingqondo, ukondla nokuqinisa. Inemisebenzi yokugqugquzela uketshezi lomzimba nokuqeda ukoma, ukumanzisa amathumbu, ukondla igazi kanye ne-yin enomsoco. Ukusetshenziswa njalo kwama-mulberry amnyama kungathuthukisa ukubona futhi kukhulule izimpawu zokukhathala kwamehlo nokoma. Amajikijolo amnyama anothile ngezinto ezihlukahlukene ezisebenzayo, okuhlanganisa ama-flavonoid, ama-alkaloid, ama-polyphenols, nama-benzofuran. Ucwaningo lwesimanje lwesayensi yezemithi lubonise ukuthi i-mulberry emnyama ine-anti-isimila, i-antioxidant, iqeda ukuvuvukala, -i-viral, i-antihypertensive nemiphumela ye-hypoglycemic.
Ukuhlelwa kabusha kwe-Metabolic kungakhuthaza ukukhula nokwanda kwamangqamuzana omdlavuza. I-Serine metabolism idlala indima ebalulekile ku-tumorigenesis, futhi ukwanda komsebenzi we-serine synthesis kusheshisa i-redox homeostasis, ukuthuthwa kwe-amino acid, kanye nokuhlanganiswa kwe-nucleotide, ihlinzeka amangqamuzana omdlavuza amandla amaningi kanye nama-metabolites amaphakathi{1}}i-phosphoglycerate dehydrogenase (PHGDH) iyisilinganiso sokuqala sokulinganisa, i-cavorine synthesis ye-delysensise ye-denolyse ye-selimite- ukuhlanganiswa kwe-phosphohydroxypyruvate (3-PPyr) kusuka ku-3-phosphoglycerate (3-PG). Ucwaningo luye lwabonisa ukuthi i-PHGDH ibonakala kakhulu ezinhlobonhlobo zezimila zabantu, njenge-melanoma, umdlavuza we-pancreatic, umdlavuza womlomo wesibeletho, nomdlavuza webele ophindwe kathathu. Ukuvinjelwa kwe-PHGDH kunciphisa i-serine synthesis futhi kuvimbela ukwanda kwamaseli e-tumor, ukufuduka nokuhlasela. Ngakho-ke, ama-PHGDH inhibitors angase asebenze njengesu elisebenzayo lokwelapha umdlavuza.
Kuleli phepha, isithelo sikamalibhele omnyama sacwaningwa, futhi kwahlukaniswa izinhlanganisela ezingama-20, okuhlanganisa izinhlanganisela ezimbili ezintsha, i-moranigrineA kanye ne-morusamine. Phakathi kwazo, i-MoranigrineA iyinhlanganisela eyivelakancane ene-pyrrole-2-aldehyde kanye ne-2-arylbenzofuran units yesakhiwo, futhi ababhali baqagela indlela yayo ye-biosynthetic. I-athikili ihlole umthelela ovimbelayo wazo zonke izinhlanganisela ezihlukanisiwe ku-PHGDH, futhi yathola ukuthi i-methyl caffeate ibonise umphumela omkhulu wokuvimbela ku-PHGDH. Ukuhlaziywa kwe-Kinetic kokuvinjelwa kwe-enzyme kubonise ukuthi i-methyl caffeate yayiyi-inhibitor engancintisani ehlobene ne-substrate 3-PG futhi ivinjwe ngendlela encike ekugxilweni. Ukuhlaziywa kwe-MST kuphinde kwaqinisekisa ukusebenzisana okuqondile kwe-methyl caffeate ne-PHGDH.
Ukwengeza, i-molecular docking ibonise ukuthi i-methyl caffeate ibophezela ephaketheni le-allosteric le-PHGDH kunendawo yayo esebenzayo, ehambisana nedatha ye-enzyme kinetics. Ukuhlolwa kwamaseli kubonise ukuthi i-methyl caffeate ingavimbela ngokuqondile ukwanda kwamaseli e-HeLa; ababhali baphinde bathola ukuthi i-methyl caffeate ingakhuthaza i-apoptosis yamaseli we-HeLa futhi ibophe umjikelezo weseli. Ukuhlolwa kwe-CETSA kanye ne-siRNA kuphinde kwafakazela ukuthi i-methyl caffeate iqonde ngqo i-PHGDH. Ngesikhathi esifanayo, i-methyl caffeate inomphumela osobala wokuvimbela ukukhula kwesimila kumodeli yegundane ye-HeLa cell xenograft enobuthi obuphansi. Imiphumela engenhla ibonisa ukuthi i-methyl caffeate ingasetshenziswa njenge-PHGDH inhibitor yemvelo, ehlinzeka ngenhlanganisela ehamba phambili yocwaningo lwezidakamizwa ze-antitumor eziqondiswe ku-PHGDH, futhi i-Mnigra ingasetshenziswa njengokudla okusebenzayo kokuvimbela nokwelashwa kwe-adjuvant yomdlavuza.
