Structurally Diverse Phenolic Amides from the Fruits of Lycium barbarum with Potent α-Glucosidase, Dipeptidyl Peptidase-4 Inhibitory, and PPAR-γ Agonistic Activities.
Hui ChenWen-Jing ZhangJiang-Bo KongYun LiuYan-Le ZhiYan-Gang CaoKun DuGui-Min XueMeng LiZhen-Zhu ZhaoYan-Jun SunWei-Sheng FengZhi-Shen XiePublished in: Journal of agricultural and food chemistry (2023)
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.
Keyphrases
- molecular docking
- molecular dynamics simulations
- insulin resistance
- high resolution
- simultaneous determination
- molecular dynamics
- magnetic resonance
- ms ms
- ionic liquid
- high performance liquid chromatography
- fatty acid
- capillary electrophoresis
- mass spectrometry
- type diabetes
- density functional theory
- liquid chromatography
- metabolic syndrome
- skeletal muscle
- tandem mass spectrometry
- binding protein
- anti inflammatory