Nyob rau hauv xyoo tas los no, Dihydromyricetin (DHM), raws li ib qho flavonoid compound nrog ntau yam kev ua haujlwm lom neeg, tau kawm dav dav rau nws cov teebmeem hauv kev tiv thaiv oxidation, tiv thaiv kev mob, tiv thaiv ntshav qab zib thiab tiv thaiv qog. Tshwj xeeb, cov txheej txheem ntawm kev ua ntawm DHM hauv kev tswj hwm ntshav qab zib hom 2 (T2DM) tau txais kev txhawb nqa los ntawm ntau cov kev tshawb fawb. Kab lus no yuav tshawb txog cov txheej txheem ntawm kev nqis tes ua ntawm DHM thiab nws cov zeem muag hauvkev siv tshuaj tiv thaiv ntshav qab zib.
Molecular mechanism ntawm kev ua ntawm dihydromyricetin
1. Lub hom phiaj kwv yees thiab protein-protein interaction network (PPI)
Txhawm rau nthuav tawm lub peev xwm ntawm DHM hauv kev tiv thaiv kab mob ntshav qab zib, cov kws tshawb fawb tau siv Swiss lub hom phiaj kev kwv yees cov ntaub ntawv los tshuaj xyuas 72 lub hom phiaj muaj peev xwm ntawm DHM, thiab ua ke nrog cov phiaj xwm tsom xam ntawm T2DM kom tau txais 35 lub hom phiaj, uas yog qhov tseem ceeb rau lub tshuab. kev ua ntawm DHM hauv ntshav qab zib. Ntxiv protein-protein interaction network tsom xam (PPI) tau qhia tias 35 lub hom phiaj uas DHM tuaj yeem cuam tshuam txog kev sib cuam tshuam los ntawm 168 qhov sib txuas sib txuas los tsim kom muaj kev sib koom tes ua haujlwm. Cov ntsiab lus tseem ceeb hauv lub network no suav nrog MAPK14, PPARG thiab VEGFA, uas muaj feem cuam tshuam nrog qhov tshwm sim thiab kev loj hlob ntawm T2DM.
Lub network PPI qhia tau hais tias DHM tuaj yeem cuam tshuam nrog cov txheej txheem lom neeg mob ntshav qab zib mellitus thiab qhia txoj hauv kev los ntawm kev cuam tshuam kev cuam tshuam ntawm cov protein tseem ceeb, yog li ua tiav cov txiaj ntsig ntawm kev tswj cov ntshav qab zib.
2. GO enrichment thiab KEGG txoj kev tsom xam raws li lub network pharmacology
GO enrichment tsom xam pom tias DHM muaj ntau yam tseem ceeb ntawm cov txheej txheem lom neeg (BP) hauv T2DM, suav nrog kev tswj tsis zoo ntawm cov noob qhia, kev tswj xyuas zoo ntawm MAP kinase kev ua, angiogenesis, thiab lwm yam.; Tsis tas li ntawd, nyob rau hauv cov nqe lus ntawm molecular muaj nuj nqi (MF), DHM kuj qhia tau hais tias nws muaj enzyme khi thiab protein homodimerization. Nyob rau hauv cov nqe lus ntawm cell Cheebtsam (CC), lub luag hauj lwm ntawm DHM yog concentrated nyob rau hauv lub extracellular matrix thiab receptor complex, uas qhia tau hais tias DHM plays lub luag hauj lwm muaj peev xwm nyob rau hauv regulating cell qauv thiab muaj nuj nqi.
Cov txiaj ntsig ntawm KEGG txoj kev tsom xam pom tau tias DHM tau txhawb nqa ntau txoj hauv kev cuam tshuam nrog cov kab mob ntshav qab zib, xws li PI3K-Akt signaling pathway, IL-17 signaling pathway, thiab HIF-1 signaling pathway. Kev ua haujlwm ntawm txoj hauv kev no yog qhov tseem ceeb rau kev sib kis ntawm cov teeb liab insulin, kev tswj hwm ntawm cov lus teb inflammatory, cell metabolism thiab lwm yam kev lom neeg, ntxiv dag zog rau lub peev xwm ntawm DHM hauv kev tiv thaiv ntshav qab zib.
3. Component-target-disease-pathway network analysis
Los ntawm kev tsim lub "cov khoom siv-lub hom phiaj-tus kab mob-txoj kev" network, txoj hauv kev tseem ceeb thiab lub hom phiaj ntawm DHM thiab ntshav qab zib tau tshwm sim ntau dua. DHM lub hom phiaj tseem ceeb xws li MAPK14, PPARG thiab VEGFA tau pom tias muaj feem cuam tshuam rau ntau txoj hauv kev mob ntshav qab zib mellitus, suav nrog MAPK signaling pathway, PI3K-Akt signaling pathway thiab endocrine resistance pathway. Cov hom phiaj no ua lub luag haujlwm tseem ceeb hauv kev tswj cov cell proliferation, antioxidant thiab anti-inflammatory teb, muab kev txhawb zog rau kev tiv thaiv kab mob ntshav qab zib mechanism ntawm DHM.
Hauv lub network no, MAPK signaling pathway thiab PI3K-Akt signaling pathway yog suav tias yog txoj hauv kev tseem ceeb rau DHM kom cuam tshuam rau cov ntshav qab zib. Tshwj xeeb, MAPK txoj hauv kev ua lub luag haujlwm tseem ceeb hauv kev loj hlob ntawm tes thiab kev sib txawv, thiab cov lus teb los tiv thaiv oxidative kev ntxhov siab, thaum txoj kev PI3K-Akt ncaj qha cuam tshuam rau cov teeb liab ntawm insulin thiab tuaj yeem tswj hwm glycogen synthesis, cell survival thiab qabzib uptake.
Physiological thiab biochemical teebmeem ntawm dihydromyricetin rau cov nas mob ntshav qab zib
Hauv kev sim tsiaj, DHM tau pom cov teebmeem hypoglycemic tseem ceeb ntawm cov nas mob ntshav qab zib (xws li db / db nas). Tom qab kev kho DHM, cov ntshav qabzib cov nas tau txo qis (p<0.001), and the levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) in their serum were significantly reduced (p<0.0001), while the level of high-density lipoprotein cholesterol (HDL-C) was increased. These results show that DHM has a significant improvement effect on the lipid profile and metabolic disorders of diabetic mice.
Tsis tas li ntawd, DHM kuj tau txo cov ntshav qab zib rau lub siab puas tsuaj los ntawm kev txo qis oxidative kev ntxhov siab (ALT, AST thiab ROS qib) hauv daim siab thiab nce qib ntawm antioxidant enzyme GSH-Px. Cov teebmeem no qhia tau tias DHM tuaj yeem txo qhov kev ntxhov siab oxidative ntawm cov nas ntshav qab zib thiab tiv thaiv daim siab ua haujlwm.
Cov txiaj ntsig ntawm kev nthuav qhia gene
Gene qhia cov ntaub ntawv ntxiv tau pom tias DHM tuaj yeem tswj tau qhov kev qhia ntawm ntau yam metabolism hauv cov noob hauv daim siab ntawm cov nas mob ntshav qab zib. DHM tau txhim kho cov txheej txheem metabolic ntawm cov nas los ntawm inhibiting kev qhia ntawm cov noob caj noob ces thiab txhim kho qhov kev qhia ntawm cov noob caj noob ces. Cov koob tshuaj ntau ntawm DHM tau pom qhov koob tshuaj tseem ceeb nyob rau hauv kev qhia txog kev tswj hwm ntawm cov tshuaj metabolic tshwj xeeb (xws li VEGFA thiab MAPK14), qhia tias DHM muaj kev tswj hwm muaj peev xwm rau cov noob metabolic.
Bidirectional kev cai ntawm dihydromyricetin nyob rau hauv PI3K / AKT thiab MAPK txoj kev taw qhia
Los ntawm kev kawm ntawm PI3K / AKT thiab MAPK signaling pathways, nws tau pom tias DHM tuaj yeem qhib txoj hauv kev PI3K / AKT thiab inhibit MAPK signaling pathway. Txoj cai bidirectional no yog tus yuam sij rau nws txoj kev tiv thaiv kab mob ntshav qab zib. Hauv daim siab cov ntaub so ntswg ntawm cov nas mob ntshav qab zib, DHM tau txhim kho qhov kev qhia ntawm AKT protein ntau hauv PI3K / AKT txoj kev taw qhia, yog li txhim kho cov ntshav qabzib thiab txhim kho insulin rhiab heev. Nyob rau tib lub sijhawm, DHM tau txo qis MEK cov protein nyob rau hauv txoj kev MAPK, qhia tias nws muaj peev xwm tiv thaiv cov kab mob ntshav qab zib mellitus.
Kev ua kom lub PI3K / AKT signaling txoj hauv kev pab ua kom cov piam thaj nce ntxiv thiab kev siv, thaum inhibition ntawm MAPK signaling txoj hauv kev tuaj yeem txo qhov kev tso tawm ntawm cov tshuaj tiv thaiv. Qhov kev tswj hwm thib ob no yog qhov tseem ceeb heev rau kev tswj ntshav qab zib, inflammatory teb inhibition thiab metabolic tshuav nyiaj li cas hauv cov neeg mob ntshav qab zib.
Molecular docking tsom xam
Molecular docking tsom xam ntxiv tau pom tias DHM muaj kev sib raug zoo nrog cov hom phiaj tseem ceeb, tshwj xeeb nrog cov hom phiaj xws li MMP9, MAPK14 thiab VEGFA. Kev sib txuas ntawm DHM rau cov hom phiaj no pab nws inhibit extracellular matrix degradation, tswj inflammatory teb thiab txhawb angiogenesis, yog li pab txhim kho ntshav qab zib pathology.
Cov chaw khi ntawm DHM rau cov hom phiaj no yog nyob ntawm cov amino acid residues xws li ALA{{0}} thiab LEU-243, raws li, nrog rau kev khi lub zog ntawm -10.2 kcal/mol rau 4.0 kcal/mol. Cov chaw muaj kev sib raug zoo siab no txuas ntxiv txheeb xyuas lub luag haujlwm ntawm DHM hauv kev tswj hwm cov hom phiaj ntsig txog ntshav qab zib.
Siv: Wen, X.; lwv, c;. Zhou, R.; Wang, Y.; Zhou, X.; Qin, S. Molecular Mechanism Hauv qab Cov Kev Kho Mob ntawm Dihydromyricetin ntawm Hom 2 Ntshav Qab Zib Mellitus Raws li Network Pharmacology, Molecular Docking, thiab Transcriptomics. Khoom noj khoom haus 2024, 13, 344.https://doi.org/10.3390/foods13020344
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