State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin 541004, China.
College of Pharmacy, Guilin Medical University, Guilin 541004, China.
Bioorg Chem. 2021 Jun;111:104847. doi: 10.1016/j.bioorg.2021.104847. Epub 2021 Mar 22.
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 α-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 α-glucosidase activity, with IC values ranging from 257.74 μM, 282.23 μM, and strongly inhibited the release of NO, with IC values of 9.10 μM, 9.02 μM. Moreover, compound 2 significantly downregulated the mRNA expression of iNOS, COX-2, IL-1β, NF-κB, IL-6 and TNF-α in LPS-mediated RAW 264.7 cells and markedly suppressed the protein expression of iNOS, NF-κB/p65, and COX-2. Dammarane glucoside 2 exhibited the strongest α-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 α-glucosidase inhibitory and anti-inflammatory activities, and dammarane saponins are responsible for regulating α-glucosidase, inflammatory mediators, and mRNA and the protein expression of proinflammatory cytokines, which could be meaningful for discovering new antidiabetic agents.
糖尿病是由慢性炎症引起的，影响着全世界数百万人。山茶叶在传统民间茶中被广泛用作糖尿病的治疗药物，但降糖成分仍有待进一步研究。本研究检测了α-葡萄糖苷酶抑制和抗炎活性，以评估其对糖尿病的作用，并通过生物活性导向分离山茶叶，鉴定了二十个达玛烷型皂苷，包括 11 个新的达玛烷型皂苷（1-11）。通过光谱方法阐明了这些分离物的结构。生物活性测定结果表明，化合物 1 和 2 强烈抑制α-葡萄糖苷酶活性，IC 值范围为 257.74 μM 和 282.23 μM，强烈抑制 NO 的释放，IC 值分别为 9.10 μM 和 9.02 μM。此外，化合物 2 显著下调 LPS 介导的 RAW 264.7 细胞中 iNOS、COX-2、IL-1β、NF-κB、IL-6 和 TNF-α的 mRNA 表达，并显著抑制 iNOS、NF-κB/p65 和 COX-2 的蛋白表达。达玛烷糖苷 2 表现出最强的α-葡萄糖苷酶抑制和抗炎活性。此外，还研究了达玛烷型皂苷的结构-活性关系（SAR）。综上所述，山茶叶表现出显著的α-葡萄糖苷酶抑制和抗炎活性，达玛烷型皂苷可调节α-葡萄糖苷酶、炎症介质以及促炎细胞因子的 mRNA 和蛋白表达，这对于发现新的抗糖尿病药物具有重要意义。
