草果、草豆蔻和薄荷中抑制α-葡萄糖苷酶和PTP1B 活性成分研究

	草果、草豆蔻和薄荷中抑制α-葡萄糖苷酶和PTP1B 活性成分研究; The α-Glucosidase and PTP1B Inhibitors in Amomum tsaoko, Alpinia katsumadai and Mentha canadensis
	何小凤
导师	陈纪军
摘要	As one of the most serious chronic diseases in the world, diabetes mellitus (DM) is caused by insulin deficiency and its decreased secretion in organism. More than 422 million people are suffering from DM worldwide, which leads to 1.6 million deaths every year. A series of therapeutic targets and medicines have been discovered along with the in-depth study of DM. α-Glucosidase inhibitors are the preferred medicines against postprandial hyperglycemia, the clinical use of which is an efficient method to treat insulin-independent DM. Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of insulin signal transduction, and has been regarded as one of the hot targets in recent DM study. Thus, the R&D of natural α-glucosidase and PTP1B inhibitors is showing necessary and urgent. Our preliminary bioassay showed that Amomum tsao-ko, Alpinia katsumadai and Mentha canadensis all possessed significant α-glucosidase inhibitory activity and A. tsao-ko also had obvious PTP1B inhibitory activity. To further reveal the hypoglycemic constituents of the above three plants, the thesis focused on a systematic phytochemical investigation guided by α-glucosidase inhibitory activity. Through various chromatographic methods including silica gel, sephadex LH-20, Rp-C18, MCI gel CHP 20P, preparative TLC and semi-prep HPLC, as well as modern spectroscopic techniques involving HRESIMS, 1D and 2D NMR, IR and UV together with calculated ECD methods, 265 compounds were isolated and identified as diarylheptanoid, diarylheptanoid-chalcone conjugate, diarylheptanoid- flavanone conjugate, diarylheptanoid dimer, flavanol-monoterpene conjugate, flavanol-fatty alcohol conjugate and so on. Among them, 153 new compounds were elucidated. Bioassay on α-glucosidase inhibitory activity suggested 111 compounds possessed stronger inhibitory effect (IC50 < 100 μM) than the positive control acarbose (IC50, 200 μM), and 27 compounds exhibited comparable activity (IC50, 100~250 μM) to acarbose. In addition, some flavanols in A. tsao-ko had obvious inhibitory effect against PTP1B, four of which demonstrated the most significant activity (IC50 < 100 μM; IC50 of the positive control suramin sodium was 200 μM). Enzyme kinetics studies showed that diarylheptanoids were noncompetitive-type inhibitors against α-glucosidase while flavanols were mixed-type. The thesis systemically investigated the chemical constituents of three plants, A. tsao-ko, A. katsumadai and M. canadensis, firstly revealed the dual inhibitory activity of flavanols against α-glucosidase and PTP1B, and also discovered the α-glucosidase inhibitory activity of diversified diarylheptanoids. These results provided preliminary chemical and pharmacological basis in applying diarylheptanoids and flavanols as new α-glucosidase and PTP1B inhibitors, as well as new scientific basis for expanding the application of the above three plants and searching new antidiabetic candidates of natural origin.
	2020-05
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74128
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	何小凤. 草果、草豆蔻和薄荷中抑制α-葡萄糖苷酶和PTP1B 活性成分研究, The α-Glucosidase and PTP1B Inhibitors in Amomum tsaoko, Alpinia katsumadai and Mentha canadensis[D],2020.

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