该研究采用超高速离心和蔗糖密度梯度离心分离纯化石榴皮胞外囊泡(pomegranate peel-derived extracellular nanovesicles，PPENs)并对其进行形貌结构表征。体外α-葡萄糖苷酶抑制实验及胰岛素抵抗(insulin resistance，IR)HepG2细胞模型测试显示，PPENs具有良好的抗糖尿病活性，α-葡萄糖苷酶抑制IC50为(35。3±1。1)μg·mL-1，显著优于阳性药品阿卡波糖(acarbose)。PPENs在100μg·mL-1可以显著提高IR细胞的葡萄糖吸收量。通过色谱-质谱联用开展PPENs脂质组、蛋白质组及代谢物分析，对microRNA(miRNA)序列进行鉴定和人类靶基因预测分析。分析结果表明，PPENs含有丰富的脂质和转运蛋白，为PPENs的跨组织运输与分布提供物质基础。京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Ge-nomes，KEGG)通路富集分析提示，脂质和miRNA可能是PPENs发挥抗糖尿病活性的关键成分。
Anti-diabetic active constituents of pomegranate peel-derived extracellular nanovesicles
Pomegranate peel-derived extracellular nanovesicles(PPENs)were isolated and purified by ultra-high speed centrifuga-tion and sucrose density gradient centrifugation.Their morphology and structure were characterized.In vitro α-glucosidase inhibition assay and model test of insulin resistance(IR)in HepG2 cells showed that PPENs had good anti-diabetic activity.The IC50 value ofα-glucosidase inhibition was(35.3±1.1)µg·mL-1,significantly better than the positive drug acarbose.At a concentration of 100 μg·mL-1,PPENs could increase the glucose absorption of IR cells significantly.Lipidome,proteome,and metabolite analysis of PPENs were performed using chromatography-mass spectrometry.MicroRNA(miRNA)sequences were identified,and target genes of miRNA were predicted.The analysis results indicated that PPENs contained abundant lipids and transport proteins,providing a material basis for the transportation and distribution of PPENs in tissue.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis suggested that lipids and miRNAs may be the key components of PPENs to exert anti-diabetic activity.
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