Antidiabetic Stilbenes from Peony Seeds with PTP1B, α-Glucosidase, and DPPIV Inhibitory Activities
Antidiabetic Stilbenes from Peony Seeds with PTP1B, α-Glucosidase, and DPPIV Inhibitory Activities
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牡丹籽中的抗糖尿病二苯乙烯类化合物，具有 PTP1B、α-葡萄糖苷酶和 DPPIV 抑制活性
DOI：
10.1021/acs.jafc.9b01193
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发表时间：
2019-06-19
影响因子：
6.1
通讯作者：
Chen, Ji-Jun
中科院分区：
文献类型：
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作者：
Zhang, Chen-Chen;Geng, Chang-An;Chen, Ji-Jun
在生物活性测定的指导下，从牡丹籽中分离得到一个新的白藜芦醇四聚体-芍药内酯醇（paeonilactiflorol，1）和14个已知化合物（2-15）。通过HRESIMS、UV、IR、1D和2DNMR等波谱分析确定了其中的2-羟基-3-甲基-2-（3-羟基-3-甲基-3-苯基-3-甲基-4-甲基-3-苯基-3-甲基-大多数二苯乙烯类化合物对PTP 1B和α-葡萄糖苷酶的抑制作用明显，抑制效果上级优于单萜苷类化合物。特别地，二苯乙烯四聚体（1）和三聚体（8）表现出抑制PTP 1B（IC 50值为27.23和27.81 μ M）和α-葡糖苷酶（IC 50值为13.57和14.39 μ M）的高活性。除了PTP 1B和α-葡糖苷酶外，两种反式二聚体（4和5）也显示二肽基肽酶-4（DPPIV）抑制活性（55.35%和61.26%，500 μ M）。酶动力学研究表明，3和5对PTP 1B的抑制类型为非竞争性，8和10为混合性。定量分析表明，牡丹籽中主要含有二苯乙烯三聚体8（23.17 ± 0.36 mg/g）和10（15.24 ± 0.25 mg/g），它们可能是牡丹籽抗糖尿病作用的主要成分。本研究支持牡丹籽在治疗糖尿病方面的治疗潜力，并以芪类化合物为活性成分。
One unusual resveratrol tetramer, paeonilactiflorol (1), and 14 known compounds (2-15) were isolated from peony seeds (Paeonia lactiflora) under the guidance of bioassay. Paeonilactiflorol (1) was determined by extensive HRESIMS, UV, IR, 1D and 2D NMR spectroscopic analyses. Most of the stilbenes showed obvious inhibition on PTP1B and alpha-glucosidase, superior to the monoterpene glycosides. Especially, the stilbene tetramer (1) and trimer (8) exhibited high activity inhibiting both PTP1B with IC50 values of 27.23 and 27.81 mu M and alpha-glucosidase with IC50 values of 13.57 and 14.39 mu M. Two trans-dimers (4 and 5) also showed dipeptidyl peptidase-4 (DPPIV) inhibitory activity (55.35% and 61.26%, 500 mu M) in addition to PTP1B and alpha-glucosidase. Enzyme kinetic study indicated that the types of inhibition on PTP1B were noncompetitive for 3 and 5 and mixed for 8 and 10. Quantitative analysis suggested that the stilbene trimers 8 (23.17 +/- 0.36 mg/g) and 10 (15.24 +/- 0.25 mg/g) were the main contents in peony seeds and should be responsible for the antidiabetic effects. This investigation supports the therapeutic potential of peony seeds in the treatment of diabetes with stilbenes as the active constituents.