Natural phenolic compounds potentiate hypoglycemia via inhibition of Dipeptidyl peptidase IV

Abstract

Dipeptidyl peptidase IV (DPP IV) is a surface glycoprotein that can degrade glucagon like pepetide-1 (GLP-1) by decreasing blood sugar. Herbal medicines for diabetic therapy are widely used with acceptable efficacy but unsatisfied in advances. DPP IV was chosen as a template to employ molecular docking via Discovery Studio to search for natural phenolic compounds whether they have the inhibitory function of DPP IV. Then, docking candidates were validated and further performed signal pathway via Caco-2, C2C12, and AR42J cells. Lastly, a diet-induced diabetes in mice were applied to examine the efficacy and toxicity of hit natural phenolic products in long-term use (in vivo). After screening, curcumin, syringic acid, and resveratrol were found in high affinity with DPP IV enzymes. In enzymatic tests, curcumin and resveratrol showed potential inhibition of DPP IV. In vitro assays, curcumin inhibited of DPP IV activity in Caco-2 cells and ERK phosphorylation in C2C12 cells. Additionally, curcumin attenuated blood sugar in S961-treated C57BL/6 mice and in diet-induced diabetic ICR mice and long-term regulate HbA1c in diabetic mice. Curcumin targeted to DPP IV for reducing blood glucose, it possesses potential and alternative substitution of synthetic clinical drugs for the medication of diabetes.

Hypoglycemic Efficacy of Docking Selected Natural Compounds against α-Glucosidase and α-Amylase

“…Curcumin is the major constituent of turmeric ( C. longa ), that various reported activities including anti-tumour, anti-malaria, immunomodulation, and anti-diabetes effects [ 26 ]. In fact, the anti-diabetic effects of curcumin are exerted by activating the peroxisome proliferator-activated receptors γ (PPAR γ) signalling pathway and upregulating GLUT4 translocation [ 12 ], increasing insulin secretion and sensitivity, regulating glucagon synthase kinase 3 (GSK-3) [ 27 ], and inhibiting DPP-4 activity [ 28 ]. Previously, curcumin and its derivatives (curcuminoids) had been proved as α-glucosidase inhibitors in an enzymatic manner [ 29 ].…”

Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4

“…Besides, HCD and berberine interacted with Tyr 662 and Tyr 666 around the binding site and showed stronger inhibitory activities than those of rutin and quercetin. This impact could also be evaluated from the binding simulation of curcumin in a previous study [14]. This result speculated that interaction with Tyr 662 and Tyr 666 might be more important than others.…”

“…In our previous study, rutin, quercetin, and berberine showed DPP-4 inhibitory potency while docking with DPP-4 [14]. In the literature, the hypoglycemic effect of berberine has been investigated for many years.…”

“…The molecular docking of natural compounds against DPP-4 was described in a previous study [14]. Selected natural compounds were purified by Yi-Chen Chia (Department of Food Science and Technology, Tajen University, Pingtung, Taiwan).…”

“…In our previous study, 68 natural compounds were docked with DPP-4 protein module and the strength of interaction ranked by docking score. 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyathia longifolia , rutin and quercetin from Toona sinensis , and berberine from Coptis chinensis , whose docking scores were 79.257 (rutin), 68.290 (HCD), 65.341 (quercetin), and 65.248 (berberine), respectively, obtained the 1st, 3rd, 5th, and 6th places of 68 screened natural compounds [14]. The data revealed that HCD, rutin, quercetin, and berberine might strongly interact with DPP-4 and which might be potential inhibitors.…”