α-Glucosidase inhibitory and anti-inflammatory activities of dammarane triterpenoids from the leaves of Cyclocarya paliurus
α-Glucosidase inhibitory and anti-inflammatory activities of dammarane triterpenoids from the leaves of Cyclocarya paliurus
复制标题
DOI：
10.1016/j.bioorg.2021.104847
复制
发表时间：
2021-03-30
影响因子：
5.1
通讯作者：
Huang, Xishan
中科院分区：
文献类型：
--
作者：
Li, Chenguo;Deng, Shengping;Huang, Xishan
糖尿病是由慢性炎症引起的，影响着全球数百万人。青钱柳叶已被广泛应用于传统民间茶中，作为治疗糖尿病的药物，但其抗糖尿病成分仍有待进一步研究。研究了它们的α-葡萄糖苷酶抑制活性和抗炎活性，以评价它们的抗糖尿病作用，并通过生物测定引导的分离，鉴定了20个达玛烷皂苷，其中包括11个新的达玛兰皂苷(1-11)。用波谱方法对分离得到的菌株进行了结构鉴定。生物活性测定结果表明，化合物1和2对α-葡萄糖苷酶活性有较强的抑制作用，IC50值分别为257.74和282.23 mU M，对NO的释放有较强的抑制作用，IC50值分别为9.10mU M和9.02mU。化合物2能显著抑制脂多糖介导的RAW 264.7细胞诱导型一氧化氮合酶、环氧合酶-2、白介素1β、核因子-kappaB、白介素6和肿瘤坏死因子-α的基因表达，并抑制诱导型一氧化氮合酶、核因子-kappaB/p65和环氧合酶-2的蛋白表达。丹参糖苷2具有最强的α-葡萄糖苷酶抑制和抗炎活性。此外，对丹参皂苷的构效关系(SARS)进行了研究。综上所述，青钱柳叶具有显著的α-葡萄糖苷酶抑制和抗炎活性，丹参皂苷具有调节α-葡萄糖苷酶、炎症介质和促炎细胞因子的mRNA和蛋白表达的作用，这可能对发现新的抗糖尿病药物具有重要意义。
Diabetes mellitus is caused by chronic inflammation and affects millions of people worldwide. Cyclocarya paliurus leaves have been widely used in traditional folk tea as a remedy for diabetes, but the antidiabetic constituents remain to be further studied. The alpha-glucosidase inhibitory and anti-inflammatory activities were examined to evaluate their effects on diabetes mellitus, and bioassay-guided separation of C. paliurus leaves led to the identification of twenty dammarane saponins, including eleven new dammarane saponins (1-11). The structures of the isolates were elucidated by spectroscopic methods. Bioactivity assay results showed that compounds 1 and 2 strongly inhibited alpha-glucosidase activity, with IC50 values ranging from 257.74 mu M, 282.23 mu M, and strongly inhibited the release of NO, with IC50 values of 9.10 mu M, 9.02 mu M. Moreover, compound 2 significantly downregulated the mRNA expression of iNOS, COX-2, IL-1 beta, NF-kappa B, IL-6 and TNF-alpha in LPS-mediated RAW 264.7 cells and markedly suppressed the protein expression of iNOS, NF-kappa B/p65, and COX-2. Dammarane glucoside 2 exhibited the strongest alpha-glucosidase inhibitory and anti-inflammatory activities. In addition, the structure-activity relationships (SARs) of the dammarane saponins were investigated. In summary, C. paliurus leaves showed marked alpha-glucosidase inhibitory and anti-inflammatory activities, and dammarane saponins are responsible for regulating alpha-glucosidase, inflammatory mediators, and mRNA and the protein expression of proinflammatory cytokines, which could be meaningful for discovering new antidiabetic agents.