Structurally Diverse Phenolic Amides from the Fruits of Lycium barbarum with Potent α-Glucosidase, Dipeptidyl Peptidase-4 Inhibitory, and PPAR-γ Agonistic Activities

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 IC50 of 1.11–33.53 μM, 5–150 times stronger than acarbose (IC50 = 169.78 μM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-γ), with EC50 values of 10.09–44.26 μM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC50 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.

Structurally Diverse Phenylpropanamides from Cannabis Fructus and Their Potential Neuroprotective Effects

“…Compound 2 exhibited the characteristic signals of tetrahydrofuran (THF)-like lignans, manifested by the coupling constants of H-8/H-8′ (each dd, J = 9.0 and 7.8 Hz). 51,52 The placement of the methoxyl groups at C-3 and C-3′ was determined by their HMBC correlations (Figure 2). The correlations in the NOESY spectrum were observed between H-8 and (H-7′ and H-2), and H-8′ and (H-7 and H-2′) (Figure 3), indicating a 7,8-trans/8,8′-trans/7′,8′-trans relative configuration.…”

“…Moreover, the long-range correlation between H-8″ and C-9, and H-8‴ and C-9′ suggested that the two tyramine fragments were connected to the two phenylpropanoid through the amino group. Compound 2 exhibited the characteristic signals of tetrahydrofuran (THF)-like lignans, manifested by the coupling constants of H-8/H-8′ (each dd, J = 9.0 and 7.8 Hz). , The placement of the methoxyl groups at C-3 and C-3′ was determined by their HMBC correlations (Figure ). The correlations in the NOESY spectrum were observed between H-8 and (H-7′ and H-2), and H-8′ and (H-7 and H-2′) (Figure ), indicating a 7,8-trans/8,8′-trans/7′,8′-trans relative configuration. − The absolute configuration was further confirmed through the quantum chemical time-dependent density-functional theory (TDDFT) calculations of ECD.…”

Comment on “Three New Dimers and Two Monomers of Phenolic Amides from the Fruits of Lycium barbarum and Their Antioxidant Activities”

“…Fortunately, the number of articles incorporating the incorrectly elucidated structures is still limited. However, one article recently published in the Journal of Agricultural and Food Chemistry uses the incorrect structures for a docking study, which exemplifies why it is important to rectify the elucidation of these structures.…”