Chi Bingqing, Liang Xilong, Wang Lihua, Bian Yifei, Zhang Meng, Tang Zhixin, Wang Danyang, Tian Zhenhua
College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Department of Biostatistics, School of Public Health, Yale University, New Haven, CT 06489, USA.
Pharmaceuticals (Basel). 2022 Dec 15;15(12):1566. doi: 10.3390/ph15121566.
Mill. is widely distributed in Turkey, Uzbekistan and China and commonly used by the food industry to produce jam, jelly and candies. The aim of this study was to investigate the in vitro antidiabetic activity and anti-diabetic mechanism of Mill. fruit (COMF). The chemical compositions were further characterized in COMF by UPLC-Q-Orbitrap/MS and 65 components including 22 flavonoids, 16 organic acids, 11 polyphenols, 5 amino acids, 3 pentacyclic triterpenoids and 8 other compounds were identified. The antioxidant activity by DPPH scavenging method and α-glucosidase inhibitory activity were tested. Furthermore, we detected the effects of COMF extract on the proliferation activity of HUVECs, cell viability of HUVECs under HO-induced oxidative stress, and NO production. Then, molecular docking activity and α-glucosidase inhibitory activity of seven key flavonoid components selected by bioinformatics analysis and literature in the COMF were studied. Among them, quercetin showed potent inhibitory activity, kaempferol, isorhamnetin, luteolin and apigenin demonstrated moderate inhibitory activity, while rutin and epicatechin exhibited poor inhibitory activity. Subsequently, the effects of quercetin, kaempferol, isorhamnetin, leteolin and apigenin on the gene expression levels of AKT1, IL-6 and VEGFA were verified by real-time fluorescence quantification (RT-qPCR). Molecular biology result showed that different active ingredients can significantly recover the levels of AKT1, IL-6 and VEGFA in HUVECs injured by high glucose.
Mill. 在土耳其、乌兹别克斯坦和中国广泛分布，食品工业常用其生产果酱、果冻和糖果。本研究旨在探究Mill. 果实（COMF）的体外抗糖尿病活性及抗糖尿病机制。通过超高效液相色谱-四极杆-轨道阱质谱联用仪（UPLC-Q-Orbitrap/MS）对COMF中的化学成分进行了进一步表征，鉴定出65种成分，包括22种黄酮类化合物、16种有机酸、11种多酚、5种氨基酸、3种五环三萜类化合物和8种其他化合物。采用DPPH自由基清除法检测抗氧化活性，并检测α-葡萄糖苷酶抑制活性。此外，我们检测了COMF提取物对人脐静脉内皮细胞（HUVECs）增殖活性、过氧化氢（HO）诱导的氧化应激下HUVECs的细胞活力以及一氧化氮（NO）产生的影响。然后，研究了通过生物信息学分析和文献筛选出的COMF中7种关键黄酮类成分的分子对接活性和α-葡萄糖苷酶抑制活性。其中，槲皮素显示出较强的抑制活性，山奈酚、异鼠李素、木犀草素和芹菜素表现出中等抑制活性，而芦丁和表儿茶素表现出较弱的抑制活性。随后，通过实时荧光定量聚合酶链反应（RT-qPCR）验证了槲皮素、山奈酚、异鼠李素、木犀草素和芹菜素对蛋白激酶B1（AKT1）、白细胞介素-6（IL-6）和血管内皮生长因子A（VEGFA）基因表达水平的影响。分子生物学结果表明，不同活性成分可显著恢复高糖损伤的HUVECs中AKT1、IL-6和VEGFA的水平。
