Structurally Diverse Phenolic Amides from the Fruits of <i>Lycium barbarum</i> with Potent α-Glucosidase, Dipeptidyl Peptidase-4 Inhibitory, and PPAR-γ Agonistic Activities
Hui Chen, Wenjing Zhang, Jiang-Bo Kong, Yun Liu, Yanle Zhi, Yan-Gang Cao, Kun Du, Gui‐Min Xue, Meng Li, Zhen‐Zhu Zhao, Yan‐Jun Sun, Weisheng Feng, Zhishen Xie
Abstract
A total of nine new phenolic amides ( 1 – 9 ), including four pairs of enantiomeric mixtures ( 3 – 5 and 8 ), along with ten known analogues ( 10 – 19 ) were identified from the fruits of Lycium barbarum using bioassay-guided chromatographic fractionation. Their structures were elucidated by comprehensive spectroscopic and spectrometric analyses, chiral HPLC analyses, and quantum NMR, and electronic circular dichroism calculations. Compounds 5 – 7 are the first example of feruloyl tyramine dimers fused through a cyclobutane ring. The activity results indicated that compounds 1, 11, and 13 – 17 exhibited remarkable inhibition against α-glucosidase with IC 50 of 1.11–33.53 μM, 5–150 times stronger than acarbose (IC 50 = 169.78 μM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-γ), with EC 50 values of 10.09–44.26 μM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC 50 value of 47.13 μM. Furthermore, the banding manner of compounds 14 and 17 with the active site of α-glucosidase, DPPIV, and PPAR-γ was explored by employing molecular docking analysis.