Purification of Phenylpropanoids from the Scaly Bulbs of Lilium Longiflorum by CPC and Determination of Their DPP-IV Inhibitory Potentials

Abstract

The scaly bulbs of Lilium longiflorum (Liliaceae) are used as a food ingredient and a traditional medicine in East Asia. A preliminary study revealed that treatment with 100 μg/mL of the ethyl acetate fraction of this plant material inhibited dipeptidyl peptidase IV (DPP-IV) to 58.99%. Phytochemical studies were conducted to identify the active ingredient, and five compounds, namely, 1 (2.9 mg, 75.8% purity at 320 nm), 2 (12.2 mg, 97.9% purity at 320 nm), 3 (3.1 mg, 66.5% purity at 320 nm), 4 (6.8 mg, 96.9% purity at 320 nm), and 5 (6.2 mg, 90.2% purity at 320 nm) were purified from 200 mg of the ethyl acetate fraction of L. longiflorum via centrifugal partition chromatography (CPC) with a two-phase solvent system composed of chloroform/methanol/isopropanol/water (5:2:2:4, v/v/v/v) in an ascending mode. Their structures were identified as 1-O-p-coumaroyl-2-O-β-glucopyranosylglycerol (regaloside D, 1), 3,6′-O-diferuloylsucrose (2), 1-O-p-coumaroyl-2-O-β-glucopyranosyl-3-O-acetylglycerol (regaloside B, 3), 1-O-p-coumaroylglycerol (4), and 4-O-acetyl-3,6′-O-diferuloylsucrose (5), respectively, by 1H and 13C NMR and MS analysis. Compounds 2 and 5 exhibited DPP-IV inhibitory activities with IC50 values of 46.19 and 63.26 μM, respectively. Compounds 1, 3, and 4 did not show activities, indicating that biphenylpropanoids linked via the sugar moiety are more effective than phenylpropanoids with glycerol or glyceryl glucoside. This is the first report of simultaneous separation of five phenylpropanoids from L. longiflorum by CPC and evaluation of their DPP-IV inhibitory activities.

Constituents of Coreopsis lanceolata Flower and Their Dipeptidyl Peptidase IV Inhibitory Effects

“…Extensive studies on the phytochemical-based DPP-IV inhibitors were undertaken in the literature [ 19 , 20 , 21 ], and in our previous studies [ 16 , 22 ]. Flavonoids and phenolic compounds were found to be the DPP-IV inhibitors with potent to mild activities, showing IC 50 values in the range of 0.12 to 63.26 μM.…”

“…As a result, DPP-IV inhibition enhances the glucose-producing effect of GLP-1, thereby improving glucose tolerance in diabetic patients [ 18 ]. As DPP-IV inhibitors, synthetic chemical compounds or natural product-derived compounds recently represent promising drug candidates [ 16 , 19 , 20 , 21 , 22 ].…”

Metabolite Profiling and Dipeptidyl Peptidase IV Inhibitory Activity of Coreopsis Cultivars in Different Mutations

“…The tested samples dissolved in DMSO at a concentration of 10 mg/mL were subsequently diluted to a final concentration of 20 to 200 μg/mL using DMSO and were added to a 96-well plate to a final volume of 10 μL and a final concentration of 50 μM. The assay procedure is described in our previous studies [ 12 , 62 , 63 ]. Briefly, diluted assay buffer (30 μL) and diluted enzyme solution (10 μL) were added to the 96-well plate containing 10 μL of solvent (blank) or solvent-dissolved test samples.…”

“…Hence, DPP-IV inhibitors have emerged as a new class of oral anti-diabetic agents, and synthetic compounds have mainly been used in current treatments with these inhibitors [59]. However, there have also been studies that show that DPP-inhibitors are derived from natural sources as promising candidates of functional foods or pharmaceuticals [12,[60][61][62][63].…”

A Comprehensive Review and Perspective on Natural Sources as Dipeptidyl Peptidase-4 Inhibitors for Management of Diabetes

“…Treatment with the ethyl acetate fraction of L. longiflorum was shown to inhibit DPP-4. Five compounds were purified from the ethyl acetate fraction of L. longiflorum , and compounds 2 and 5 were found to exhibit DPP-4 inhibitory activity with IC 50 values of 46.19 and 63.26 µM, respectively [ 90 ].…”