6-Formyl Umbelliferone, a Furanocoumarin from Angelica decursiva L., Inhibits Key Diabetes-Related Enzymes and Advanced Glycation End-Product Formation

Abstract

Over the years, great attention has been paid to coumarin derivatives, a set of versatile molecules that exhibit a wide variety of biological activities and have few toxic side effects. In this study, we investigated the antidiabetic potential of 6-formyl umbelliferone (6-FU), a novel furanocoumarin isolated from Angelica decursiva. Numerous pharmacological activities of 6-FU have been previously reported; however, the mechanism of its antidiabetic activity is unknown. Therefore, we examined the action of 6-FU on a few candidate-signaling molecules that may underlie its antidiabetic activity, including its inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, human recombinant aldose reductase (HRAR), and advanced glycation end-product (AGE) formation (IC50 = 1.13 ± 0.12, 58.36 ± 1.02, 5.11 ± 0.21, and 2.15 ± 0.13 μM, respectively). A kinetic study showed that 6-FU exhibited mixed-type inhibition against α-glucosidase and HRAR and competitive inhibition of PTP1B. Docking simulations of 6-FU demonstrated negative binding energies and close proximity to residues in the binding pockets of those enzymes. We also investigated the molecular mechanisms underlying 6-FU’s antidiabetic effects. 6-FU significantly increased glucose uptake and decreased PTP1B expression in insulin-resistant C2C12 skeletal muscle cells. Moreover, 6-FU (0.8–100 μM) remarkably inhibited the formation of fluorescent AGEs in glucose-fructose-induced human serum albumin glycation over the course of 4 weeks. The findings clearly indicate that 6-FU will be useful in the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-related complications.

Prunin from Poncirus trifoliata (L.) Rafin Inhibits Aldose Reductase and Glucose-Fructose–Mediated Protein Glycation and Oxidation of Human Serum Albumin

“…The amount of fructosamine that was present promoted the formation of AGEs, suggesting that prunin functions to effectively lower fructosamine concentrations and mitigate some of the difficulties linked to AGEs. Numerous naturally occurring compounds can prevent the synthesis of fructosamine, according to several studies, ,,, but ours is the first to demonstrate that prunin suppresses the levels of fructosamine formation.…”

“…Usually, Arg and Lys were the primary predicted glycation sites in the protein, and the glycation of the protein was greatly influenced by the properties of its surrounding amino acids. , According to other studies, Ile, Leu, Phe, and Arg may greatly boost Lys’s reactivity in a variety of compounds containing Lys. , According to this study, the interactions between prunin and HSA involving the amino acids Ile, Leu, Lys, and Arg may have reduced the glycosylation activity of nearby potential glycation sites. It has previously been reported that a variety of small molecules, such as luteolin, ursonic acid, 6-formyl umbelliferone urolithin A, chrysin, and luteolin, ,− form hydrophobic and hydrogen bonding interactions with Arg, Leu, Val, Lys, Tyr, and Pro in HSA, thereby promoting HSA stability and inhibiting the formation of AGEs and glycation. Similar residue-binding properties were shown by prunin in this study, which may increase the stability of HSA and inhibit glycation and the production of AGE.…”

“…The inhibition of HRAR was investigated, as we have previously reported. 30 In brief, an Ultrospec 2100pro UV/vis spectrophotometer was used to measure the reduction in NADPH absorption at 340 nm over the course of 1 min in order to evaluate the AR activity. All data analyses were conducted using SWIFT II Applications software (Amersham Biosciences, NJ, USA).…”

An Arylbenzofuran, Stilbene Dimers, and Prenylated Diels–Alder Adducts as Potent Diabetic Inhibitors from Morus bombycis Leaves

“…Before the docking analysis to investigate the binding poses of compounds inside the active receptor pockets, the crystal protein structures for PTP1B (PDB ID: 1NNY for the catalytic site; 1T49 for the allosteric site) and α-glucosidase (PDB ID: 3A4A) were downloaded from the Protein Data Bank (PDB) [ 53 ]. These protein structures were confirmed using X-ray diffraction.…”

Coumarins of Lovage Roots (Levisticum officinale W.D.J.Koch): LC-MS Profile, Quantification, and Stability during Postharvest Storage

“…This information cannot be considered complete and needs additional study of the componential profile and quantification data of L. officinale coumarins. Additionally, furanocoumarins are bioactive metabolites with proven antivirus [ 40 ], antiallergic [ 41 ], antidiabetic [ 42 ], antidepressive [ 43 ], anticancer [ 44 ], and anti-inflammatory potential [ 45 ]. Thus, furanocoumarin-containing foods may be promising functional products.…”