In Silico Analysis: Anti-Inflammatory and α-Glucosidase Inhibitory Activity of New α-Methylene-γ-Lactams.

The research about α-methylene-γ-lactams is scarce; however, their synthesis has emerged in recent years mainly because they are isosters of α-methylene-γ-lactones. This last kind of compound is structurally most common in some natural products' nuclei, like sesquiterpene lactones that show biological activity such as anti-inflammatory, anticancer, antibacterial, etc., effects. In this work, seven α-methylene-γ-lactams were evaluated by their inflammation and α-glucosidase inhibition. Thus, compounds 3-methylene-4-phenylpyrrolidin-2-one (1), 3-methylene-4-(p-tolyl)pyrrolidin-2-one (2), 4-(4-chlorophenyl)-3-methylenepyrrolidin-2-one (3), 4-(2-chlorophenyl)-3-methylenepyrrolidin-2-one (4), 5-ethyl-3-methylene-4-phenylpyrrolidin-2-one (5), 5-ethyl-3-methylene-4-(p-tolyl)pyrrolidin-2-one (6) and 4-(4-chlorophenyl)-5-ethyl-3-methylenepyrrolidin-2-one (7) were evaluated via in vitro α-glucosidase assay at 1 mM concentration. From this analysis, 7 exerts the best inhibitory effect on α-glucosidase compared with the vehicle, but it shows a low potency compared with the reference drug at the same dose. On the other side, inflammation edema was induced using TPA (12-O-tetradecanoylphorbol 13-acetate) on mouse ears; compounds 1-7 were tested at 10 µg/ear dose. As a result, 1, 3, and 5 show a better inhibition than indomethacin, at the same doses. This is a preliminary report about the biological activity of these new α-methylene-γ-lactams.

Preparation of a Novel Oat ß-Glucan-Chromium(III) Complex and Its Hypoglycemic Effect and Mechanism.

This study synthesized a novel oat ß-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104 Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.

Synthesis of obovatol and related neolignan analogues as α-glucosidase and α-amylase inhibitors.

Diabetes mellitus is a metabolic disease characterized by hyperglycemia, which can be counteracted by the inhibition of α-glucosidase (α-Glu) and α-amylase (α-Amy), enzymes responsible for the hydrolysis of carbohydrates. In recent decades, many natural compounds and their bioinspired analogues have been studied as α-Glu and α-Amy inhibitors. However, no studies have been devoted to the evaluation of α-Glu and α-Amy inhibition by the neolignan obovatol (1). In this work, we report the synthesis of 1 and a library of new analogues. The synthesis of these compounds was achieved by implementing methodologies based on: phenol allylation, Claisen/Cope rearrangements, methylation, Ullmann coupling, demethylation, phenol oxidation and Michael-type addition. Obovatol (1) and ten analogues were evaluated for their in vitro inhibitory activity towards α-Glu and α-Amy. Our investigation highlighted that the naturally occurring 1 and four neolignan analogues (11, 22, 26 and 27) were more effective inhibitors than the hypoglycemic drug acarbose (α-Amy: 34.6 µM; α-Glu: 248.3 µM) with IC5O value of 6.2-23.6 µM toward α-Amy and 39.8-124.6 µM toward α-Glu. Docking investigations validated the inhibition outcomes, highlighting optimal compatibility between synthesized neolignans and both the enzymes. Concurrently circular dichroism spectroscopy detected the conformational changes in α-Glu induced by its interaction with the studied neolignans. Detailed studies through fluorescence measurements and kinetics of α-Glu and α-Amy inhibition also indicated that 1, 11, 22, 26 and 27 have the greatest affinity for α-Glu and 1, 11 and 27 for α-Amy. Surface plasmon resonance imaging (SPRI) measurements confirmed that among the compounds studied, the neolignan 27 has the greater affinity for both enzymes, thus corroborating the results obtained by kinetics and fluorescence quenching. Finally, in vitro cytotoxicity of the investigated compounds was tested on human colon cancer cell line (HCT-116). All these results demonstrate that these obovatol-based neolignan analogues constitute promising candidates in the pursuit of developing novel hypoglycemic drugs.

Design, synthesis, molecular docking study, and α-glucosidase inhibitory evaluation of novel hydrazide-hydrazone derivatives of 3,4-dihydroxyphenylacetic acid.

A series of novel Schiff base derivatives (1-28) of 3,4-dihydroxyphenylacetic acid were synthesized in a multi-step reaction. All the synthesized Schiff bases were obtained in high yields and their structures were determined by 1HNMR, 13CNMR, and HR-ESI-MS spectroscopy. Except for compounds 22, 26, 27, and 28, all derivatives show excellent to moderate α-glucosidase inhibition. Compounds 5 (IC50 = 12.84 ± 0.52 µM), 4 (IC50 = 13.64 ± 0.58 µM), 12 (IC50 = 15.73 ± 0.71 µM), 13 (IC50 = 16.62 ± 0.47 µM), 15 (IC50 = 17.40 ± 0.74 µM), 3 (IC50 = 18.45 ± 1.21 µM), 7 (IC50 = 19.68 ± 0.82 µM), and 2 (IC50 = 20.35 ± 1.27 µM) shows outstanding inhibition as compared to standard acarbose (IC50 = 873.34 ± 1.67 µM). Furthermore, a docking study was performed to find out the interaction between the enzyme and the most active compounds. With this research work, 3,4-dihydroxyphenylacetic acid Schiff base derivatives have been introduced as a potential class of α-glucosidase inhibitors that have remained elusive till now.

Effect of Phenol and Alkylamide Interaction on α-Glucosidase Inhibition and Cellular Antioxidant Activity during In Vitro Digestion: Using Szechuan Pepper (Zanthoxylum genus) as a Model.

Although recent evidence indicated significant phenol and alkylamide interaction in aqueous solutions, the gastrointestinal digestion influence of the combination remains unclear. This study aims to investigate phenol and alkylamide interaction during in vitro digestion, focusing on bioaccessibility and bioactivity, including α-glucosidase inhibition and cellular antioxidant activity. Additionally, the structural mechanism of phenol and alkylamide interaction during in vitro digestion was explored. The results indicated that the presence of phenols and alkylamides significantly increased or decreased their respective bioaccessibility, depending on the Zanthoxylum varieties. Furthermore, although antagonistic phenol/alkylamide interaction was evident during α-glucosidase inhibition, cellular oxidative stress alleviation, and antioxidant gene transcription upregulation, this effect weakened gradually as digestion progressed. Glycoside bond cleavage and the methylation of phenols as well as alkylamide isomerization and addition were observed during digestion, modifying the hydrogen bonding sites and interaction behavior. This study provided insights into the phenol/alkylamide interaction in the gastrointestinal tract.

Polyketides with α-glucosidase inhibitory and neuroprotective activities from Aspergillus versicolor associated with Pedicularis sylvatica.

Aspergillus versicolor, an endophytic fungus associated with the herbal medicine Pedicularis sylvatica, produced four new polyketides, aspeversins A-D (1-2 and 5-6) and four known compounds, O-methylaverufin (2), aversin (3), varilactone A (7) and spirosorbicillinol A (8). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by calculated electronic circular dichroism (ECD) and Mo2(AcO)4-induced CD data. Compound 5 was found to exhibit α-glucosidase inhibitory activity with an IC50 value of 25.57 µM. An enzyme kinetic study indicated that 5 was a typical uncompetitive inhibitor toward α-glucosidase, which was supported by a molecular docking study. Moreover, compounds 1-3 and 5 also improved the cell viability of PC12 cells on a 1-methyl-4-phenylpyridinium (MPP+)-induced Parkinson's disease model, indicating their neuroprotective potential as antiparkinsonian agents.

New α-Glucosidase Inhibitors from the Whole Plant of Hypericum beanii Based on Ligand Fishing and Molecular Networking Analysis.

In this work, a new rapid and targeted method for screening α-glucosidase inhibitors from Hypericum beanii was developed and verified. Ten new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperlagarol A-J (1-10), and nine known PPAPs (11-19) were obtained from H. beanii. Their structures were identified by using comprehensive analyses involving mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, nuclear magnetic resonance spectroscopy, and electron capture dissociation calculations. 1 and 2 are two new rare 2,3-seco-spirocyclic PPAPs, 3 and 4 are two novel 12,13-seco-spirocyclic PPAPs, 5 and 6 are two novel spirocyclic PPAPs, 7 and 8 are two new unusual spirocyclic PPAPs with complex bridged ring systems, and 9 and 10 are two novel nonspirocyclic PPAPs. α-GC inhibitory activities of all isolated compounds were tested. Most of them displayed inhibitory activities against α-glucosidase, with the IC50 values ranging from 6.85 ± 0.65 to 112.5 ± 9.03 µM. Moreover, the inhibitory type and mechanism of the active compounds were further analyzed using kinetic studies and molecular docking.

Mechanisms of inhibition of advanced glycation end-products (AGEs) and α-glucosidase by Heliotropium bacciferum: Spectroscopic and molecular docking analysis.

Diabetes mellitus is characterized by hyperglycemia that makes insulin more prone to glycation and form advanced glycation end products (AGEs). Here, we report the effect of glyoxal (GO) on the formation of AGEs using human insulin as model protein and their structural modifications. The present investigation also reports the anti-AGE potential of Heliotropium bacciferum (Leaf) extracts. The phytochemical analysis of H. bacciferum revealed that free phenolic extract contains higher amount of total phenolic (3901.58 ± 17.06 mg GAE/100 g) and total flavonoid content (30.41 ± 0.32 mg QE/100 g) when compared to bound phenolic extract. Naringin and caffeic acid were identified as the major phenolic ingredients by UPLC-PAD method. Furthermore, bound phenolics extract showed significantly higher DPPH and superoxide radicals scavenging activity (IC50 17.53 ± 0.36 µg/mL and 0.306 ± 0.038 mg/ mL, respectively) (p ≤ 0.05). Besides, the bound phenolics extract also showed significant (p ≤ 0.05) chelating power (IC50 0.063) compared to free phenolic extract. In addition, bound phenolic extract could efficiently trap GO under physiological conditions. Spectroscopic investigation of GO-modified insulin illustrated changes in the tertiary structure of insulin and formation of AGEs. On the other hand, no significant alteration in secondary structure was observed by far UV-CD measurement. Furthermore, H. bacciferum extract inhibited α-glucosidase activity and AGEs formation implicated in diabetes. Molecular docking analysis depicted that GO bind with human insulin in both chains and forms a stable complex with TYR A: 14, LEU A:13, ASN B:3, SER A:12 amino acid residues with binding energy of - 2.53 kcal/mol. However, caffeic acid binds to ASN A:18 and GLU A:17 residues of insulin with lower binding energy of -4.67 kcal/mol, suggesting its higher affinity towards human insulin compared to GO. Our finding showed promising activity of H. bacciferum against AGEs and its complications. The major phenolics like caffeic acid, naringin and their derivatives could be exploited for the drug development for management of AGEs in diabetes.

Bioactive α-Pyrone Analogs from the Endophytic Fungus Diaporthe sp. CB10100: α-Glucosidase Inhibitory Activity, Molecular Docking, and Molecular Dynamics Studies.

Two α-pyrone analogs were isolated from the endophytic fungus Diaporthe sp. CB10100, which is derived from the medicinal plant Sinomenium acutum. These analogs included a new compound, diaporpyrone F (3), and a known compound, diaporpyrone D (4). The structure of 3 was identified by a comprehensive examination of HRESIMS, 1D and 2D NMR spectroscopic data. Bioinformatics analysis revealed that biosynthetic gene clusters for α-pyrone analogs are common in fungi of Diaporthe species. The in vitro α-glucosidase inhibitory activity and antibacterial assay of 4 revealed that it has a 46.40% inhibitory effect on α-glucosidase at 800 µM, while no antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), Mycolicibacterium (Mycobacterium) smegmatis or Klebsiella pneumoniae at 64 µg/mL. Molecular docking and molecular dynamics simulations of 4 with α-glucosidase further suggested that the compounds are potential α-glucosidase inhibitors. Therefore, α-pyrone analogs can be used as lead compounds for α-glucosidase inhibitors in more in-depth studies.

Probing benzenesulfonamide-thiazolidinone hybrids as multitarget directed ligands for efficient control of type 2 diabetes mellitus through targeting the enzymes: α-glucosidase and carbonic anhydrase II.

Diabetes mellitus is a chronic metabolic disorder characterized by improper expression/function of a number of key enzymes that can be regarded as targets for anti-diabetic drug design. Herein, we report the design, synthesis, and biological assessment of two series of thiazolidinone-based sulfonamides 4a-l and 5a-c as multitarget directed ligands (MTDLs) with potential anti-diabetic activity through targeting the enzymes: α-glucosidase and human carbonic anhydrase (hCA) II. The synthesized sulfonamides were evaluated for their inhibitory activity against α-glucosidase where most of the compounds showed good to potent activities. Compounds 4d and 4e showed potent inhibitory activities (IC50 = 0.440 and 0.3456 µM), comparable with that of the positive control (acarbose; IC50 = 0.420 µM). All the synthesized derivatives were also tested for their inhibitory activities against hCA I, II, IX, and XII. They exhibited different levels of inhibition against these isoforms. Compound 4d outstood as the most potent one against hCA II with Ki equals to 7.0 nM, more potent than the reference standard (acetazolamide; Ki = 12.0 nM). In silico studies for the most active compounds within the active sites of α-glucosidase and hCA II revealed good binding modes that can explain their biological activities. MM-GBSA refinements and molecular dynamic simulations were performed on the top-ranking docking pose of the most potent compound 4d to confirm the formation of stable complex with both targets. Compound 4d was screened for its in vivo antihyperglycemic efficacy by using the oral glucose tolerance test. Compound 4d decreased blood glucose level to 217 mg/dl, better than the standard acarbose (234 mg/dl). Hence, this revealed its synergistic mode of action on post prandial hyperglycemia and hepatic gluconeogenesis. Thus, these benzenesulfonamide thiazolidinone hybrids could be considered as promising multi-target candidates for the treatment of type II diabetes mellitus.

Anti-Inflammatory and α-Glucosidase Inhibitory Triterpenoid with Diverse Carbon Skeletons from the Fruits of Rosa roxburghii.

The fruits of Rosa roxburghii Tratt. are edible nutritional food with high medicinal value and have been traditionally used as Chinese folk medicine for a long time. In this study, 26 triterpenoids including four new pentacyclic triterpenoids, roxbuterpenes A-D (1, 4, 5, and 24), along with 22 known analogues (2, 3, 6-23, 25, and 26), were isolated from the fruits of R. roxburghii. Their chemical structures were determined on the basis of extensive spectroscopic analyses (including IR, HRESIMS and NMR spectroscopy). The absolute configuration of roxbuterpene A (1) was determined by an X-ray crystallographic analysis. This is the first report of the crystal structure of 5/6/6/6/6-fused system pentacyclic triterpenoid. Notably, roxbuterpenes A and B (1 and 4) possessed the A-ring contracted triterpenoid and nortriterpenoid skeletons with a rare 5/6/6/6/6-fused system, respectively. Compounds 1-7, 11, 13-15, 18-20, 24, and 25 exhibited moderate or potent inhibitory activities against α-glucosidase. Compounds 2, 4, 6, 11, and 14 showed strong activities against α-glucosidase with IC50 values of 8.4 ± 1.6, 7.3 ± 2.2, 13.6 ± 1.4, 0.9 ± 0.4, and 12.5 ± 2.4 µM, respectively (positive control acarbose, 10.1 ± 0.8 µM). Compounds 13, 14, and 16 moderately inhibited the release of NO (nitric oxide) with IC50 values ranging from 25.1 ± 2.0 to 51.4 ± 3.1 µM. Furthermore, the expressions of TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6) were detected by ELISA (enzyme-linked immunosorbent assay), and compounds 13, 14, and 16 exhibited moderate inhibitory effects on TNF-α and IL-6 release in a dose-dependent manner ranging from 12.5 to 50 µM.

Effective α-glycosidase inhibitors based on polyphenolic benzothiazole heterocycles.

α-Glycosidase inhibition is one of the main approaches to treat Diabetes mellitus. Polyphenolic moieties are known to be responsible for yielding exhibit potent α-glycosidase inhibitory effects. In addition, compounds containing benzothiazole and Schiff base functionalities were previously reported to show α-glycosidase inhibition. In this paper, the synthesis of seven new phloroglucinol-containing benzothiazole Schiff base derivatives through the reaction of 6-substituted-2-aminobenzothiazole compounds with 2,4,6-trihydroxybenzaldehyde using acetic acid as a catalyst was reported. The synthesized compounds were characterized using spectroscopic methods such as FT-IR, 1H NMR, 13C NMR, and elemental analysis. The synthesized compounds were evaluated for their inhibitory effects on α-glycosidase, compounds 3f and 3g were found to show significant inhibitory properties when compared to the positive control. The IC50 values of 3f and 3g were calculated as 24.05 ± 2.28 and 18.51 ± 1.19 µM, respectively. Kinetic studies revealed that compounds 3f and 3g exhibited uncompetitive mode of inhibition against α-glycosidase. Molecular modeling predicted druglikeness for the title compounds and underpinned the importance of phloroglucinol hydroxyls for interacting with the key residues of α-glycosidase.

Antisolvent precipitation for the synergistic preparation of ultrafine particles of nobiletin under ultrasonication-homogenization and evaluation of the inhibitory effects of α-glucosidase and porcine pancreatic lipase in vitro.

To further enhance the application of nobiletin (an important active ingredient in Citrus fruits), we used ultrasonic homogenization-assisted antisolvent precipitation to create ultrafine particles of nobiletin (UPN). DMSO was used as the solvent, and deionized water was used as the antisolvent. When ultrasonication (670 W) and homogenization (16000 r/min) were synergistic, the solution concentration was 57 mg/mL, and the minimum particle size of UPN was 521.02 nm. The UPN samples outperformed the RN samples in terms of the inhibition of porcine pancreatic lipase, which was inhibited (by 500 mg/mL) by 68.41 % in the raw sample, 90.34 % in the ultrafine sample, and 83.59 % in the positive control, according to the data. Fourier transform infrared spectroscopy analysis revealed no chemical changes in the samples before or after preparation. However, the crystallinity of the processed ultrafine nobiletin particles decreased. Thus, this work offers significant relevance for applications in the realm of food chemistry and indirectly illustrates the expanded application potential of nobiletin.

Efficient biotransformation of naringenin to naringenin α-glucoside, a novel α-glucosidase inhibitor, by amylosucrase from Deinococcus wulumuquiensis.

Amylosucrase (ASase) efficiently biosynthesizes α-glucoside using flavonoids as acceptor molecules and sucrose as a donor molecule. Here, ASase from Deinococcus wulumuqiensis (DwAS) biosynthesized more naringenin α-glucoside (NαG) with sucrose and naringenin as donor and acceptor molecules, respectively, than other ASases from Deinococcus sp. The biotransformation rate of DwAS to NαG was 21.3% compared to 7.1-16.2% for other ASases. Docking simulations showed that the active site of DwAS was more accessible to naringenin than those of others. The 217th valine in DwAS corresponded to the 221st isoleucine in Deinococcus geothermalis AS (DgAS), and the isoleucine possibly prevented naringenin from accessing the active site. The DwAS-V217I mutant had a significantly lower biosynthetic rate of NαG than DwAS. The kcat/Km value of DwAS with naringenin as the donor was significantly higher than that of DgAS and DwAS-V217I. In addition, NαG inhibited human intestinal α-glucosidase more efficiently than naringenin.

Structural modification of tanshinone IIA and their α-glucosidase inhibitory activity.

α-Glucosidase is one of the therapeutic approaches for treating type 2 diabetes mellitus. Almost 95 % of diabetes patients worldwide have been diagnosed with type 2 diabetes, resulting in 1.5 million fatalities each year. Newly synthesized oxazole-based tanshinone IIA derivatives (1a-n) were designed and evaluated for their inhibitory activity against α-glucosidase enzyme. Eight compounds (1a-d, 1f-g, 1j, and 1m) demonstrated excellent inhibition with IC50 values ranging from 0.73 ± 0.11 to 9.46 ± 0.57 µM as compared to tanshinone IIA (IC50 = 11.39 ± 0.77 µM) and standard acarbose (IC50 = 100.00 ± 0.95 µM). Among this series, 1j bearing two hydroxyls group over the phenyl ring was identified as the most potent α-glucosidase inhibitor with IC50 value of 0.73 ± 0.11 µM. Molecular docking simulations were done for the most active compound to identify important binding modes responsible for inhibition activity of α-glucosidase. In addition, the kinetic study was also performed to understand the mode of inhibition.

The antihyperglycemic potential of pyrazolobenzothiazine 1, 1-dioxide novel derivative in mice using integrated molecular pharmacological approach.

Diabetes Mellitus is a metabolic disease characterized by elevated blood sugar levels caused by inadequate insulin production, which subsequently leads to hyperglycemia. This study was aimed to investigate the antidiabetic potential of pyrazolobenzothiazine derivatives in silico, in vitro, and in vivo. Molecular docking of pyrazolobenzothiazine derivatives was performed against α-glucosidase and α-amylase and compounds were selected based on docking score, bonding interactions and low root mean square deviation (RMSD). Enzyme inhibition assay against α-glucosidase and α-amylase was performed in vitro using p-nitrophenyl-α-D-glucopyranoside (PNPG) and starch substrate. Synthetic compound pyrazolobenzothiazine (S1) exhibited minimal conformational changes during the 100 ns MD simulation run. S1 also revealed effective IC50 values for α-glucosidase (3.91 µM) and α-amylase (8.89 µM) and an enzyme kinetic study showed low ki (- 0.186 µM, - 1.267 µM) and ki' (- 0.691 µM, - 1.78 µM) values with the competitive type of inhibition for both enzymes α-glucosidase and α-amylase, respectively. Moreover, studies were conducted to check the effect of the synthetic compound in a mouse model. A low necrosis rate was observed in the liver, kidney, and pancreas through histology analysis performed on mice. Compound S1 also exhibited a good biochemical profile with lower sugar level (110-115 mg/dL), increased insulin level (25-30 µM/L), and low level of cholesterol (85 mg/dL) and creatinine (0.6 mg/dL) in blood. The treated mice group also exhibited a low % of glycated haemoglobin (3%). This study concludes that S1 is a new antidiabetic-agent that helps lower blood glucose levels and minimizes the complications associated with type-II diabetes.

Phytochemical Profile and Bioactivity of Bound Polyphenols Released from Rosa roxburghii Fruit Pomace Dietary Fiber by Solid-State Fermentation with Aspergillus niger.

This study aimed to investigate the phytochemical profile, bioactivity, and release mechanism of bound polyphenols (BPs) released from Rosa roxburghii fruit pomace insoluble dietary fiber (RPDF) through solid-state fermentation (SSF) with Aspergillus niger. The results indicated that the amount of BPs released from RPDF through SSF was 17.22 mg GAE/g DW, which was significantly higher than that achieved through alkaline hydrolysis extraction (5.33 mg GAE/g DW). The BPs released through SSF exhibited superior antioxidant and α-glucosidase inhibitory activities compared to that released through alkaline hydrolysis. Chemical composition analysis revealed that SSF released several main compounds, including ellagic acid, epigallocatechin, p-hydroxybenzoic acid, quercetin, and 3,4-dihydroxyphenylpropionic acid. Mechanism analysis indicated that the disruption of tight structure, chemical bonds, and hemicellulose was crucial for the release of BPs from RPDF. This study provides valuable information on the potential application of SSF for the efficient release of BPs from RPDF, contributing to the utilization of RPDF as a functional food ingredient.

New Pyranone Derivatives and Sesquiterpenoid Isolated from the Endophytic Fungus Xylaria sp. Z184.

The fungus Xylaria sp. Z184, harvested from the leaves of Fallopia convolvulus (L.) Á. Löve, has been isolated for the first time. Chemical investigation on the methanol extract of the culture broth of the titles strain led to the discovery of three new pyranone derivatives, called fallopiaxylaresters A-C (1-3), and a new bisabolane-type sesquiterpenoid, named fallopiaxylarol A (4), along with the first complete set of spectroscopic data for the previously reported pestalotiopyrone M (5). Known pyranone derivatives (6-11), sesquiterpenoids (12-14), isocoumarin derivatives (15-17), and an aromatic allenic ether (18) were also co-isolated in this study. All new structures were elucidated by the interpretation of HRESIMS, 1D, 2D NMR spectroscopy, and quantum chemical computation approach. The in vitro antimicrobial, anti-inflammatory, and α-glucosidase-inhibitory activities of the selected compounds and the crude extract were evaluated. The extract was shown to inhibit nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, with an inhibition rate of 77.28 ± 0.82% at a concentration of 50 µg/mL. The compounds 5, 7, and 8 displayed weak antibacterial activity against Staphylococcus areus subsp. aureus at a concentration of 100 µM.

Inhibition of α-glucosidase activity and intestinal glucose transport to assess the in vivo anti-hyperglycemic potential of dodecyl-acylated phlorizin and polydatin derivatives.

A diet containing natural active compounds that can inhibit the hydrolytic activity of α-glucosidase on carbohydrates and intestinal glucose absorption is an effective means of controlling postprandial hyperglycemia. Phlorizin and polydatin as phenolic glycosides have a high affinity for the catalytic site of α-glucosidase, but exhibited unsatisfactory competitive inhibitory capacity, with an IC50 of 0.97 and >2 mM, respectively. However, dodecyl-acylated derivatives of phlorizin and polydatin exerted α-glucosidase inhibitory capacity, with an IC50 of 55.10 and 70.95 µM, respectively, which were greatly enhanced and much stronger than that of acarbose with an IC50 of 2.46 mM. The SPR assay suggested the high affinity of dodecyl phlorizin and dodecyl polydatin to α-glucosidase with equilibrium dissociation constant (KD) values of 12.0 and 7.9 µM, respectively. Both dodecyl phlorizin and dodecyl polydatin reduced the catalytic ability of α-glucosidase by reversible noncompetitive and uncompetitive mixed inhibition, which bind noncovalently to the allosteric site 2 through hydrogen bonds and hydrophobic interactions, thereby inducing the secondary structure unfolding and intrinsic fluorescence quenching of α-glucosidase. Confocal microscopy detection visually showed significant inhibitory effects on FITC-labeled glucose uptake in intestinal Caco-2 cells by phlorizin, polydatin, dodecyl phlorizin and dodecyl polydatin. In addition, based on the differentiated Caco-2 cell monolayer model, dodecyl phlorizin and dodecyl polydatin suppressed intestinal glucose transport more effectively than phlorizin and polydatin, suggesting that they were promising in vivo hypoglycemic active compounds.

Phytochemical Profiling and Assessment of Antidiabetic Activity of Curcuma Angustifolia Rhizome Methanolic Extract: An In Vitro and In Silico Analysis.

Curcuma angustifolia Roxb. is a plant with medicinal potential, traditionally used to treat different diseases. The present study aimed to determine the antidiabetic activity of C. angustifolia rhizome in vitro and in silico. The methanolic extract of C. angustifolia rhizome was analyzed by FTIR and GC-MS to determine the phytochemicals present. The antidiabetic potential of the extract was evaluated by different assays in vitro. The extract inhibited both α-amylase and α-glucosidase enzymes and the glucose diffusion through the dialysis membrane in a concentration-dependent manner with IC50 values of 530.39±0.09, 293.75±0.11, and 551.74±0.3 µg/ml respectively. The methanolic extract also improved yeast cell's ability to take up glucose across plasma membranes and the adsorption of glucose. The findings were supported by molecular docking studies. The results showed that the methanol extract of C. angustifolia rhizome has significant antidiabetic activity and thus can be also studied to isolate the potential compound with antidiabetic activities.