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Objective: The study commenced with the conversion of 4-(1H-indol-3-yl)butanoic acid (I) into ethyl 4-(1H-indol-3-yl)butanoate (II), succeeded by the synthesis of the hydrazide nucleophile, 4-(1H-indol-3-yl)butanohydrazide (III). Methods: Following this, nucleophilic addition reactions of (III) with various electrophilic aldehydes (IVa–IVg) were conducted to yield the targeted derivatives (Va–Vg/Vʹa–Vʹg). The structural elucidation of all synthesized compounds relied on IR, 1H, 13C NMR, HMBC, and CHN analysis. Results and Discussion: Evaluation of the inhibitory effects of these heterocyclic butanohydrazides (Va–Vg/Vʹa–Vʹg) against the α-glucosidase enzyme revealed significant inhibition by compounds (Vg/Vʹg) compared to the standard. Conclusions: Hemolytic analysis indicated mild cytotoxicity towards red blood cell membranes, indicating the potential of these molecules as nontoxic medicinal scaffolds for skin pigmentation and related disorders. [ABSTRACT FROM AUTHOR]

The carbazole-3-carbaldehyde 2, produced by N-ethyl carbazole via Vilsmeier-Haack reaction, was subjected to Dakin type oxidation with H2O2 and H2SO4 in methanol to produce the carbazole-3-ol 3. The reaction of 3 with a range of commercially available α-haloketones 4a–f in the presence of Al2O3 as catalyst in xylene led to their regio-selective cyclization to afford the furo[2,3-c]carbazoles 5a–f. Identification of the furo[2,3-c]carbazoles 5a–f were performed through 1H NMR,13C NMR, FT-IR and high resolution mass spectrometry. Single crystal X-ray diffraction analysis was employed to further confirm the structures of the some of the targeted compounds. In vitro antidiabetic activities of the newly synthesized furocarbazoles 5a–e were investigated utilizing α-glucosidase and α-amylase enzymes. The biological evaluation revealed the obvious efficiencies of the targeted molecules toward the α-glucosidase enzyme inhibition with the potent IC50 values compared to the standard acarbose. In the case of α-glucosidase inhibition, the furo[2,3-c]carbazoles chloro substituted 5c and nitro substituted 5f were found to be more potent than acarbose with the values of 215.0 and 162.70 μM, respectively. On the other hand, the compound 5f was found to be only promising candidate for α-amylase enzyme but not as effective as the standard acarbose. [ABSTRACT FROM AUTHOR]

Diabetes mellitus has emerged as a pressing global public health concern in the 21st century, necessitating the exploration of effective and safer therapeutic alternatives to conventional synthetic anti-diabetic medications. This study aimed to comprehensively evaluate the anti-diabetic potential of Castanopsis tribuloide s through a multi-faceted approach encompassing in vitro , in vivo , and in silico experiments. In vitro assessments revealed that the methanol extract of C. tribuloides bark (CtbME) exhibited remarkable α-glucosidase inhibitory activity, as demonstrated by a low IC 50 value of 550 μg/mL, surpassing that of acarbose (600 μg/mL). Furthermore, CtbME administration led to a significant and dose-dependent reduction in hyperglycemic blood glucose levels. Twenty-three secondary metabolites were identified in GC-MS analysis. Molecular docking analysis was employed to elucidate the molecular interactions between C. tribuloides constituents and α-glucosidase. Rutin hydrate, catechin hydrate, and betulin exhibited higher binding affinity than acarbose, where rutin hydrate demonstrated exceptional stability throughout molecular dynamics simulation (MDS), affirming the accuracy of the docking data. The findings of this research underscore the potential of C. tribuloides as a source of anti-diabetic agents and provide valuable insights into the molecular mechanisms underlying its efficacy. [Display omitted] • CtbME exhibited remarkable α-glucosidase inhibitory activity. • CtbME significantly reduced hyperglycemic blood glucose levels in diabetic mice. • GC-MS analysis of CtbME identified 23 secondary metabolites. • Rutin hydrate and betulin showed strong binding affinity to α-glucosidase. • The α-glucosidase inhibitory mechanism was confirmed by MD simulation. [ABSTRACT FROM AUTHOR]

Two previously undescribed dihydrochalcones, 4,2′-dihydroxy- [2″, 2″-dimethylpyrano (3″, 4″: 4′, 5′]) dihydrochalcone (1) and 4, 2′, 4′, 2″-tetrahydroxy-5′-(3″-methylbut-3″-enyl) dihydrochalcone (2), along with six known compounds (3 - 8) were isolated from chloroform-methanol (1:1) extract of Baphia Massaiensis twigs. Their chemical structures were determined using NMR analysis, mass spectrometry, electronic circular dichroism (ECD), density functional theory (DFT) calculations, and a thorough comparison with reported data from the literature. All the isolated compounds (1−8) were assessed for their antioxidant activities, α-amylase and α-glucosidase inhibition effects. Dihydrochalcone 1 showed significant antioxidant activity with IC 50 value of 118.8 ± 2.95 µM, and a more potent antioxidant activity was exhibited by compounds 3 and 6 with IC 50 values of 84.3 ± 0.07 µM and 62.1 ± 1.59 µM, respectively, compared to the positive control, gallic acid with IC 50 value of 92.9 µM. Dihydrochalcone 2 showed moderate inhibition against α-amylase and α-glucosidase with IC 50 values of 44.0 ± 4.83 µM and 51.7 ± 9.72 µM compared to the standard acarbose with IC 50 values of 22.9 ± 0.92 µM and 31.5 ± 0.63 µM, respectively. Molecular docking studies of the new dihydrochalcones 1 and 2 , revealed the active binding sites which support the observed α-amylase and α-glucosidase inhibitory effects. [Display omitted] • Two undescribed dihydrochalcones were isolated from Baphia massaiensis. • The structures were confirmed by extensive spectroscopic analyses. • Compounds 1 and 2 showed significant inhibitory activities against α-amylase and α-glucosidase. • Compounds 1 , 3 and 6 also showed potent antioxidant activities. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of low expression of α-glucosidase (GAA) on morphology, proliferation, inflammatory response, and oxidative stress response of pancreatic β-cells in order to investigate the potential role of GAA in the pathogenesis of diabetes mellitus. Methods The expression of GAA in βTC6 cells was interfered by siRNA1,2,3 and 4, respectively. As a result, the interference effect of siRNA4 was the best, and it was used as the interference sequence in subsequent experiments. βTC6 cells were randomly divided into the siRNA group, negative control group (NC group) and blank control group(Con group), respectively. Cells in the siRNA group were transfected with siRNA4 sequence to reduce the expression of GAA, cells in the negative control group were transfected with siRNANC sequence, and cells in the Con group were not treated. After 24, 48, 72 and 96 h of cell culture, the cell proliferation of each group was detected by CCK-8. They were cultured for 48 h, the number and morphology of cells in each group were observed by inverted microscope, the inflammatory factors IL-6 and IL-1β protein in cells were detected by Western blotting, and the content of reactive oxygen species (ROS) in cells was detected by immunofluorescence. Results Compared with the Con and NC groups, the cells increased, the intercellular space became smaller under the microscope, the OD values of cells increased at 24, 48, 72, and 96 h of culture, and the levels of IL-6 and ROS decreased after 48 h of culture in the siRNA group (all P<0. 01) . No significant differences were found in these indicators between the Con and NC groups(all P>0. 05). Conclusions Low expression of GAA can lead to alterations in cell morphology, enhanced proliferative capacity, and diminished inflammatory and oxidative stress responses of pancreatic β-cells. GAA may participate in the pathogenesis of diabetes by changing the morphology of pancreatic β-cells and enhancing inflammatory and oxidative stress responses. [ABSTRACT FROM AUTHOR]

AbstractAlpha glucosidases are multifunctional glycoside hydrolases with hydrolysis and transglycosylation ability. It can be utilized for the glycosidic bond synthesis or glycosylation of Ascorbic acid/Vitamin C to its stable analogue, Ascorbic acid 2 glucoside (AA2G), a compound with wide applications in cosmetics and pharma. The application of α-glucosidases for industrial scale transglycosylation is limited due to the low transglycosylation yield of free enzymes. Enzyme immobilization techniques could enable the development of efficient, reusable catalysts. Only a few glycoside hydrolases have been studied in immobilized form for transglycosylation reactions, and α-glucosidases are probably the least explored in this form. Transglycosylation activity of immobilized α-glucosidase from Aspergillus carbonarius BTCF 5 was studied for AA2G synthesis, where different immobilization techniques like calcium alginate encapsulation, adsorption on chitosan beads, covalent cross-linking on magnetic nanoparticles, and cross-linked enzyme aggregates (CLEA) were employed for the immobilization. The immobilization yield of calcium alginate encapsulated enzyme, enzyme immobilized on Fe-MNP support, enzyme immobilized on chitosan beads and as CLEA were 107%, 99%, 46% and 486%, respectively. CLEA was identified as the best immobilization technique for this bi-substrate reaction due to the high immobilization yield and activity retention (30% activity retained after 5 consecutive cycles). Enzyme immobilization increased the transglycosylation activity by 38%, yielding 118 mM AA2G against 72 mM by the free enzyme. This indicates the potential of immobilized α-glucosidase as a catalyst for synthesizing AA2G at an industrial scale. [ABSTRACT FROM AUTHOR]

Background: Mucuna pruriens var. utilis (Wall. ex Wight) belonging to the family Fabaceae. Renowned for its diverse array of phytochemicals, this plant has been historically employed in the treatment of various ailments. The objectives of this study are to evaluate the anti-diabetic, anti-inflammatory, and antioxidant properties of the optimized M. pruriens var. utilis seed extract. Methods: The in-vitro anti-inflammatory activity of M. pruriens var. utilis ethanolic extracts was scrutinized using the Human Red Blood Cell (HRBC) method. To evaluate antioxidant activity, ABTS and DPPH assays were employed. Furthermore, the antidiabetic activity was assessed through α-amylase and α-glucosidase inhibition assays. Results: In the ethanolic extract of M. pruriens var. utilis numerous phytoconstituents were found by doing a phytochemical analysis (alkaloids, flavonoids, phenols, saponins, steroids, glycosides, tannins). The total phenolic and flavonoid content were determined to be 112.07 ± 1.21 mg of gallic acid equivalents GAE/g and 101.41 ± 1.08 mg of quercetin equivalents QE/g respectively. In this investigation ethanolic extract of M. pruriens var. utilis exhibited a high anti-inflammatory, antioxidant and antidiabetic activities in a dose-dependent manner. The M. pruriens var. utilis extract shows that anti-inflammatory activity 32.26 ± 3.23%, potent antioxidant effect by ABTS radical scavenging assay IC50 67.46 ± 1.45 µg/mL and DPPH radical scavenging assay IC50 63.34 ± 2.27 µg/mL and in addition, showed promising antidiabetic potential by inhibiting α-amylase IC50 33.42 ± 1.35 µg/mL and α-glucosidase IC50 28.34 ± 1.41 µg/mL. Conclusion: These findings provide additional support for the traditional medicinal use of M. pruriens var. utilis in treating inflammation, oxidative stress, and diabetes mellitus. [ABSTRACT FROM AUTHOR]

Diabetes Mellitus (DM) is linked to various factors causing cardiovascular diseases, with uncontrolled postprandial hyperglycemia being a direct contributor. α‐Glucosidase inhibitors (AGIs) aid in reducing postprandial hyperglycemia, potentially mitigating cardiovascular risks. In order to synthesize novel chemical scaffolds with possible α‐glucosidase inhibition activity, a series of novel soritin sulfonamide derivatives were synthesized. The soritin hydrazide was treated with various aryl sulfonyl chlorides to obtain targeted compounds (1–16). Findings suggested that all compounds have better α‐glucosidase inhibition compared to standard drugs, acarbose (2187.00 ± 1.25 μM) and 1‐deoxynojirimycin (334.90 ± 1.10 μM), with IC50 values ranging from 3.81 ± 1.67 μM to 265.40 ± 1.58 μM. The most potent analog was Compound 13, a trichloro phenyl substituted compound, with IC50 value of 3.81 ± 1.67 μM. Structure–activity relationship (SAR) showed that introducing an additional chlorine group into the parent nucleus increases the potency. The docking studies validated that Compound 13 established hydrogen bonds with the active site residues Asp214, Glu276, and Asp349, while being further stabilized by hydrophobic interactions, providing an explanation for its high potency. [ABSTRACT FROM AUTHOR]

In reaction to the expanding predominance of diabetes mellitus, curcumin nanoparticles stacked on carboxymethyl cellulose (CMC) composite were effectively synthesized, characterized, and examined utilizing UV/Vis and FTIR spectroscopy combined with transmission electron microscopy (TEM). The bioactivity of curcumin (Cur), carboxymethyl cellulose (CMC), and curcumin nanoparticles stacked with carboxymethyl cellulose (CUR-CMC) was tried through atomic docking approval as an α-amylase and α-glucosidase inhibitor. The conclusion illustrated that the curcumin-supported CMC is more potent than CUR itself self the validation presented is compared with acarbose as a reference molecule and then CUR-CMC can presented as promising in curing hyperglycemia by decreasing the absorption of glucose. [ABSTRACT FROM AUTHOR]

Pistacia species (P. spp) have been used as a treatment for various diseases, including diabetes and inflammation. This study aimed to identify the main components of flavonoids in Pistacia species and evaluate the effect of aqueous extracts of P. spp on pancreatic enzymes and on cancer cells associated with obesity in colon and rectum. HPLC was used to identify the major components of flavonoids. The potent inhibitory effect of Pistacia species against pancreatic α-amylase, α-glucosidase and lipase was examined. The antiproliferative efficacy of the plant extract against several colorectal cancer cell lines were then measured. The main flavonoids component found in Pistacia species are quercetin-3-β-D-glucoside, rutin, kaempferol and vitexin. The starch blockade IC50 (µg/mL) of Pistacia species in a descending order were: P. lentiscus leaves: 1.09±0.01; P. atlantica leaves: 0.96±0.09 and P. atlantica fruits: 0.48±0.02. Pistacia species exerted promising inhibition effect for pancreatic lipase (PL). Besides the aglycones of P. atlantica leaves, all the tested aqueous extracts exerted appreciably novel antiproliferative activity against the tested colorectal cancer cell lines. This study provides useful indication for the Pistacia species as a potential novel therapeutic agent against diabesity and cancer. [ABSTRACT FROM AUTHOR]

Kombucha is a fermented tea drink using a symbiotic culture of bacteria and yeast. This drink has been widely used to maintain blood sugar levels. Meanwhile, leaf boiled water of Syzygium polyanthum (Wight) Walp. has been used as an alternative medicine for diabetes mellitus in Indonesia. If this herb is made into kombucha, it may have higher antihyperglycemic activity than kombucha from tea leaves. However, there are no scientific reports of antihyperglycemic activity from S. polyanthum leaf kombucha by inhibiting alpha-glucosidase. This study aims to determine the activity and kinetics inhibition of S. polyanthum leaves kombucha against α-glucosidase. Samples were prepared at varying concentrations (12.5, 25, 37.5, 50 g/L), while phytochemical components in the products were identified, and the inhibitory activity as well as kinetics were comprehensively analyzed. In silico evaluations were conducted to further explore the inhibitory activity. The results showed that the products contained secondary metabolites such as flavonoids, saponins, and tannins. The inhibitory activity against α-glucosidase ranged from 81.05 to 89.41%. The inhibition mechanism was identified as uncompetitive, with a Michaelis-Menten constant (KM) of 0.1357 mM and a vmax value of 27.7008 U/ml minute. Several metabolites showed promising inhibition potential due to their strong binding interactions with α-glucosidase, including hydrogen bonding (H-bond), hydrophobic interactions, van der Waals forces, and electrostatic forces. Additionally, two metabolites, farnesol and α-pinene, were found to interact with other human proteins. These observations showed the potential of S. polyanthum leaves kombucha as a health-promoting beverage that might aid blood sugar control in diabetic individuals. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is the condition represented by persistent hyperglycaemia, owing to the altered glucose metabolism. The current research aims to assess the capabilities of strains of lactic acid bacteria (LAB) that were obtained from fermented Ananas comosus (A. comosus) and Carica papaya (C. papaya) (non-dairy sources) as probiotics for the prevention of DM. The capacity of the strains to endure or survive extreme conditions was evaluated using bile tolerance using oxgall at varying concentrations, hydrophobicity, coaggregation ability, adhesion ability, and hemolytic activity, and their survival rate in gastric and intestinal juices. The LAB strains demonstrated the following results: phenol (>7 Log CFU/mL), acid-bile conditions (6.53–7.11 Log CFU/mL), gastric and intestinal juice tolerance (6.18–7.33 Log CFU/mL), thereby fulfilling the requirements to be a prospective probiotic agent. The LAB strains showed characteristics of cell surface hydrophobicity (≥ 40 %), autoaggregation (≥ 70 %), and coaggregation (≤ 48 %). Furthermore, they demonstrated antioxidant activity (≥ 59 %) as well as the ability to lower blood sugar levels by inhibiting α-glucosidase (≤ 57 %) and α-amylase (≤ 64 %). The development of antidiabetic probiotics from fermented papaya and pineapple has several potential uses. These probiotics may be used as functional foods or supplements to improve glycemic control in individuals with DM. They may also be used as adjunct therapies to conventional diabetes treatments to enhance their efficacy. The results of this research may pave way for creating probiotic products that function as food additives or supplements, with the aim of enhancing health and preventing long-term illnesses like diabetes. Additionally, probiotics have been proven to boost intestinal health, regulate the immune system, and decrease inflammation. [Display omitted] • LAB from fermented pineapple and papaya show antidiabetic potential. • LAB exhibit resilience to gastrointestinal conditions, meeting probiotic norms. • Strains display notable probiotic traits like hydrophobicity and adhesion. • Antioxidant activity and α-glucosidase & α-amylase inhibition suggest blood sugar reduction. • Pineapple and papaya offer promising non-dairy sources for functional foods. [ABSTRACT FROM AUTHOR]

Summary: To address the adverse effects of current hypoglycaemic drugs and the limited effect of individual extracts, this research investigated the inhibitory effect of combined green tea extract (GTE) and coffee (CE) on α‐amylase (α‐AMY) and α‐glucosidase (α‐GLU) and their inhibitory mechanisms. The inhibitory effects of single extracts and the complexes on α‐AMY and α‐GLU activities were compared by the principle of equivalence line. The results showed that the complexes had a good synergistic inhibition effect on both α‐AMY and α‐GLU at GTE: CE = 4:1 (w/w). Fluorescence spectroscopy and circular dichroism spectroscopy indicated that the complexes of GTE: CE = 4:1 (w/w) altered the secondary and tertiary structures of α‐AMY and α‐GLU more than the individual extracts, resulting in a synergistic inhibitory effect. The orthogonal experiments showed that tea polyphenols (TP) and coffee polyphenols (CP) were the main components responsible for the synergistic inhibitory effect of the two extracts. [ABSTRACT FROM AUTHOR]

Summary: In order to investigate the hypoglycaemic mechanism and potential applications of four hypoglycaemic flavonoid glycosides, namely myricitrin, Cyanidin‐3‐O‐glucoside (C3G), hyperoside and quercitrin in Myrica rubra pomace, the stability of these four flavonoid glycosides and their binding mechanisms were studied using molecular docking. The results demonstrated that pH value affects on the stability of these four components in M. rubra pomace. C3G exhibited the most significant inhibitory effect on α‐glucosidase at pH 5, with myricitrin, hyperoside and quercitrin showing the highest inhibitory effect at pH 7. Moreover, an increase in temperature and storage time reduced the inhibitory effect of these four glycosidic components on α‐glucosidase. Molecular docking analysis revealed that myricitrin formed hydrogen bonds with the active site residues of α‐glucosidase, namely Phe550, Ile552, Asp555, Ser574 and Arg576, and also engaged in hydrophobic interactions with Lys551. Hyperoside formed hydrogen bonds with α‐glucosidase, formed hydrophobic interactions with Lys50 and exhibited π‐cation interaction with Lys53. Quercitrin formed hydrogen bonds with α‐glucosidase, formed hydrophobic interactions with Lys500 and established salt bridges with Lys50. C3G formed hydrogen bonds and hydrophobic interactions with α‐glucosidase and showed π‐π interactions with Phe301. These findings will provide valuable insights for the application of these four chemicals. [ABSTRACT FROM AUTHOR]

Gingerols are phenolic biomedical compounds found in ginger (Zingiber officinale) whose low aqueous solubility limits their medical application. To improve their solubility and produce novel glucosides, an α -glucosidase (glycoside hydrolase) from Agrobacterium radiobacter DSM 30147 (Ar G) was subcloned, expressed, purified, and then confirmed to have additional α -glycosyltransferase activity. After optimization, the Ar G could glycosylate gingerols into three mono-glucosides based on the length of their acyl side chains. Compound 1 yielded 63.0 %, compound 2 yielded 26.9 %, and compound 3 yielded 4.37 %. The production yield of the gingerol glucosides optimally increased in 50 mM phosphate buffer (pH 6) with 50 % (w/v) maltose and 1000 mM Li+ at 40 °C for an 24-h incubation. The structures of purified compound 1 and compound 2 were determined as 6-gingerol-5- O - α -glucoside (1) and novel 8-gingerol-5- O - α -glucoside (2), respectively, using nucleic magnetic resonance and mass spectral analyses. The aqueous solubility of the gingerol glucosides was greatly improved. Further assays showed that, unusually, 6-gingerol-5- O - α -glucoside had 10-fold higher anti-inflammatory activity (IC 50 value of 15.3 ± 0.5 μM) than 6-gingerol, while the novel 8-gingerol-5- O - α -glucoside retained 42.7 % activity (IC 50 value of 106 ± 4 μM) compared with 8-gingerol. The new α -glucosidase (Ar G) was confirmed to have acidic α -glycosyltransferase activity and could be applied in the production of α -glycosyl derivatives. The 6-gingerol-5- O - α -glucoside can be applied as a clinical drug for anti-inflammatory activity. [Display omitted] [ABSTRACT FROM AUTHOR]

The traditional herb American ginseng (Panax quinquefolium L.) can be processed into two common products: dried American ginseng (DAG) and red American ginseng (RAG), which have well-established hypoglycemic activity, making it a functional food as well. However, the mechanism by which the main active ingredients inhibit α-glucosidase, a crucial target for hypoglycemic drugs, remains unclear. In this research, we employed ultra-high-performance liquid chromatography coupled with quadrupole orbitrap mass spectrometry (UHPLC-Q-Orbitrap/MS) to analyze the chemical composition of ethanol extracts of dried American ginseng (EDAG) and red American ginseng (ERAG). Subsequent in vitro experiments were conducted to assess the α-glucosidase inhibitory activity of EDAG and ERAG. Comparative enzymatic kinetics analyses were performed as well. Molecular docking analysis revealed the interaction between the differential saponins and α-glucosidase, further validated through verification experiments. Among the total 47 identified saponins, 9 were characterized by OPLS-DA as differentially expressed between EDAG and ERAG. Notably, ERAG exhibited more robust α-glucosidase inhibitory activity than EDAG. Enzyme inhibition kinetics revealed that both products displayed reversible mixed-type inhibition on α-glucosidase, suggesting their inhibitory effects are associated with saponin composition. Molecular docking studies demonstrated that all 9 differential saponins exhibited inhibitory effects on α-glucosidase. Verification studies substantiated ginsenosides like Rb1, Rd, and others as inhibitors of α-glucosidase. These findings contribute to a more comprehensive understanding of processed American ginseng and provide valuable insights for developing glucose-lowering functional foods. [ABSTRACT FROM AUTHOR]

α-Glucosidase is an important target for type II diabetes treatment, and the search for natural α-glucosidase inhibitors is currently a hot topic in functional food research. Camellianin A is the main flavonoid in the leaves of Adinandra nitida, but research on its inhibition of α-glucosidase is rarely reported. In view of this, the present study systematically investigated the inhibitory impact of camellianin A on α-glucosidase, combining the fluorescence method and molecular docking to explore their interaction, aiming to reveal the relevant inhibitory mechanism. The results indicated that camellianin A possessed excellent α-glucosidase inhibitory activity (IC50, 27.57 ± 0.59 μg/mL), and van der Waals force and hydrogen bonding dominated the binding process between camellianin A and α-glucosidase, with a binding-site number of 1. A molecular docking experiment suggested that camellianin A formed hydrogen bonding with Glu771, Trp391, Trp710, Gly566, Asp568, and Phe444 of α-glucosidase, consistent with the thermodynamic result. Our result can provide a reference for the development of natural α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

The digestive properties of starch are crucial in determining postprandial glycaemic excursions. Genistein, an active phytoestrogen, has the potential to influence starch digestion rates. We investigated the way genistein affected the digestive properties of starch in vitro. We performed enzyme kinetics, fluorescence spectroscopy, molecular docking, and molecular dynamics (MD) simulations for analysing the inhibitory properties of genistein on starch digestive enzymes as well as clarifying relevant mechanism of action. Our findings demonstrated that, following the addition of 10% genistein, the contents of slowly digestible and resistant starches increased by 30.34% and 7.18%, respectively. Genistein inhibited α-amylase and α-glucosidase, with half maximal inhibitory concentrations of 0.69 ± 0.06 and 0.11 ± 0.04 mg/mL, respectively. Genistein exhibits a reversible and non-competitive inhibiting effect on α-amylase, while its inhibition on α-glucosidase is a reversible mixed manner type. Fluorescence spectroscopy indicated that the presence of genistein caused declining fluorescence intensity of the two digestive enzymes. Molecular docking and MD simulations showed that genistein binds spontaneously to α-amylase via hydrogen bonds, hydrophobic interactions, and π-stacking, whereas it binds with α-glucosidase via hydrogen bonds and hydrophobic interactions. These findings suggest the potential for developing genistein as a pharmacologic agent for regulating glycaemic excursions. [ABSTRACT FROM AUTHOR]

Two new cyclic peptides, named as cyclogeobomptides A (1) and B (2) were isolated from the roots of Stachys geobombycis C. Y. Wu. Compounds 1 and 2 are both made up of eight amino acids. The structures of them were established on the basis of the spectral data, including mass spectrometry, 2D NMR, and X-ray crystallography. Cyclogeobomptides A and B were proved to have obvious inhibitory activities against α-glucosidase with the IC50 values of 26.00 and 19.16 μM, respectively. [ABSTRACT FROM AUTHOR]

Background: Peach gum (PG) is an exudate of the peach tree (Prunus persica of the Rosaceae family), which consists primarily of polysaccharides with a large molecular weight and branching structure. Consequently, PG can only swell in water and does not dissolve easily, which severely limits its application. Current conventional extraction methods for PG polysaccharide (PGPS) are time consuming and inefficient. This study investigated the impact of ultrasonic‐assisted extraction (UAE) on PGPS structure and conformation, and their relationship to hypoglycemic activity in vitro. Results: In comparison with conventional aqueous extraction, UAE enhanced PGPS yielded from 28.07–32.83% to 80.37–84.90% (w/w) in 2 h. It drastically decreased the molecular size and conformational parameters of PGPS, including weight‐average molecular weight (Mw), number‐average molecular weight (Mn), z‐average radius of gyration (Rg), hydrodynamic radius (Rh) and instrinsic viscosity ([η]) values. Peach gum polysaccharide conformation converted extended molecules to flexible random coil chains or compact spheres with no obvious primary structure alteration. Furthermore, UAE altered the flow behavior of PGPS solution from that of a non‐Newtonian fluid to that of a Newtonian fluid. As a result, PGPS treated with UAE displayed weaker inhibitory activity than untreated PGPS, mostly because UAE weakens the binding strength of PGPS to α‐glucosidase. However, this negative effect of UAE on PGPS activity was compensated by the increased solubility of polysaccharide. This enabled PGPS to achieve a wider range of doses. Conclusion: Ultrasonic‐assisted extraction is capable of degrading PGPS efficiently while preserving its primary structure, resulting in a Newtonian fluid solution. The degraded PGPS conformations displayed a consistent correlation with their inhibitory effect on α‐glucosidase activity. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objectives: Oxidative stress is implicated in several metabolic cascades involved in glucose control. Hence, investigating antioxidant and antidiabetic activities is crucial for discovering an effective diabetes mellitus (DM) agent. This study was aimed at probing the therapeutic efficacy of hydro-ethanolic extract of Combretum paniculatum (HECP) and gas chromatography-flame ionization detector (GC-FID)-identified phytochemicals as novel agents for DM. Methods: We determined the total phenols, flavonoids, and antioxidant vitamins in HECP using standard methods. A GC-FID was used to decipher phytochemicals of HECP. The antioxidant and antidiabetic activities of HECP were assessed using in vitro and in silico approaches. Results: The results revealed that HECP is affluent in phenols, flavonoids, and vitamin E and demonstrated engaging antioxidant activities in 1,1-diphenyl-2-picryl-hydroxyl (DPPH; IC50 = 0.83 µg/mL), thiobarbituric acid-reactive substances TBARS; IC50 = 2.28 µg/mL), and ferric-reducing antioxidant power assay (FRAP; IC50 = 2.89 µg/mL). Compared with the reference drug, acarbose, HECP exhibited good α-amylase and α-glucosidase inhibitory capacity, having IC50 values of 14.21 and 13.23 µg/mL, respectively, against 13.06 and 11.71 µg/mL recorded for acarbose. More so, the extract's top 6 scoring phytochemicals (rutin, kaempferol, epicatechin, ephedrine, naringenin, and resveratrol) had strong interactions with amino acid residues within and around α-amylase and α-glucosidase active site domains. All the compounds but rutin had favourable drug-like characteristics, pharmacokinetics, and safety profiles when compared with acarbose. Conclusion: Altogether, our results vindicate the use of this herb in treating DM locally and reveal that it has pharmaceutically active components that could be used as novel leads in the development of DM drugs. [ABSTRACT FROM AUTHOR]

The α-glucosidase from Schwanniomyces occidentalis (GAM1p) was expressed in Komagataella phaffii to about 70 mg/L, and its transferase activity studied in detail. Several isomaltooligosaccharides (IMOS) were formed using 200 g/L maltose. The major production of IMOS (81.3 g/L) was obtained when 98% maltose was hydrolysed, of which 34.8 g/L corresponded to isomaltose, 26.9 g/L to isomaltotriose, and 19.6 g/L to panose. The addition of glucose shifted the IMOS synthesis towards products containing exclusively α(1 → 6)-linkages, increasing the production of isomaltose and isomaltotriose about 2–4 fold, enabling the formation of isomaltotetraose, and inhibiting that of panose to about 12 times. In addition, the potential of this enzyme to glycosylate 12 possible hydroxylated acceptors, including eight sugars and four phenolic compounds, was evaluated. Among them, only sucrose, xylose, and piceid (a monoglucosylated derivative of resveratrol) were glucosylated, and the main synthesised products were purified and characterised by MS and NMR. Theanderose, α(1 → 4)-D-glucosyl-xylose, and a mixture of piceid mono- and diglucoside were obtained with sucrose, xylose, and piceid as acceptors, respectively. Maximum production of theanderose reached 81.7 g/L and that of the glucosyl-xylose 26.5 g/L, whereas 3.4 g/L and only 1 g/L were produced of the piceid mono- and diglucoside respectively. Key points: • Overexpression of a yeast α-glucosidase producing novel molecules. • Yeast enzyme producing the heterooligosaccharides theanderose and glucosyl-xylose. • Glycosylation of the polyphenol piceid by a yeast α-glucosidase. [ABSTRACT FROM AUTHOR]

In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC50 = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure–activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose. [ABSTRACT FROM AUTHOR]

Current antidiabetic medications have a plethora of harmful side effects, and most of the drugs do not contain 1,3,4-oxadiazole moiety. Therefore, research into the development of novel drugs which contain 1,3,4-oxadiazole moiety with fewer side effects is necessary. Novel fluorine-incorporated 1,3,4-oxadiazole derivatives (1c–1n) were synthesized, characterized, and evaluated for α-amylase and α-glucosidase enzyme inhibitor activity. An in vivo Drosophila melanogaster model and an in vitro system were used to investigate its antidiabetic properties, further, which were characterized by 1HNMR, MASS, and FT-IR. Spectroscopic techniques and DFT are used to calculate more geometrically optimized molecule structures using the B3LYP technique. The compounds were tested against the α-glucosidase and α-amylase enzymes. Among different compounds tested, compounds 1i (IC50 = 54.83 µg/ml), 1k (IC50 = 64.95 µg/ml), 1m (IC50 = 64.78 µg/ml), and 1n (IC50 = 66.30 µg/ml) showed significant α-amylase inhibitor efficacy compared to the acarbose (IC50 = 35.17 µg/ml); compounds 1m (IC50 = 74.64 µg/ml) and 1i (IC50 = 60.35 µg/ml) exhibited significant α-glucosidase inhibitory action compared to acarbose (IC50 = 46.06 µg/ml). The docking study exhibited that compound 1i creates six hydrogen bonds and compound 1m forms three hydrogen bonding contacts at the active site of the enzyme (PDBID:4w93). The obtained results are demonstrated that compounds 1i, 1m, 1n, and 1k had greater antidiabetic activities and can be further taken into consideration for antidiabetic therapeutic interventions. [ABSTRACT FROM AUTHOR]

Flavonoids based on the flavone 1– 3 and a biflavanoid 4 with a flavan nucleus were isolated from Beilschmiedia obscura (Stapf). These compounds which include 5- hydroxy - 7,8-dimethoxyflavanone (5), (2 S,4 R)-5, 6,7-trimethoxyflavan-4-ol (6), beilschmieflavonoid B (7), (2 R ,3 S)-5,6,7-trimethoxyflavan-3-ol (8), as well as pipyahyine (9), (E , E)-1,6-bis(4-hydroxy-3-methoxyphenyl) hexa-1,5-diene-3,4-dione (10), β-sitosterol (11), pentadecanoic acid (12), pentadecan-1-ol (13), stearic acid (14) and docosane-1,2,4-triol (15), were evaluated as α-glucosidase inhibitors. The most abundant compound 5 , was structurally modified by acetylation to compound 16 and NaBH 4 reduction to compound 17 which represent two new derivatives of this compound class. These compounds 5–10 , 16–17 including kaempferol 18 , and epicatechin 19 were screened for α-glucosidase from Bacillus stearothermophyllus and showed good inhibitory activity with IC 50 values = (30.55±0.12, 31.8±0.12, 32.47±0.17, 46.53±0.16, 36.43±0.12, 33, 48±0,12, 32.63±0.11 and 43.31±0.12 µM respectively) compared to acarbose (IC 50 = 63.77±0.08 µM) as reference drug. Molecular docking and SAR studies further confirmed the plausible binding interactions between the flavonoids and the enzyme α-glucosidase. The results show that these compounds bind effectively to the active site of the protein X-ray structure 3wy1, which is in accordance of the observed α-glucosidase inhibitory activity. [Display omitted] • To develop potent anti-diabetic agents, a series of flavonoids were designed and evaluated against the enzyme α-glucosidase. • 16 compounds isolated from Beilschmiedia obscura (Stapf) including ten flavonoids were involved in our studies. • The flavonoids showed more potent inhibitory activity and were chemically transformed for structure activity relationship. • Plausible binding interactions between these flavonoids and α-glucosidase target were confirmed through molecular docking. • The modified compounds were less active confirming that the hydroxyl and keto groups were important pharmacophores. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Home Economics of Japan is the property of Japan Society of Home Economics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Chinese Institute of Food Science & Technology is the property of Journal of Chinese Institute of Food Science & Technology Periodical Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Natural functional and bioactive compounds extracted from agricultural wastes using green techniques have attracted great attention due to their health benefits, numerous potential applications and less environmental impacts. Therefore, this study aimed to co-optimize the processes of ultrasound-microwave assisted extraction (UMAE) and enzyme-ultrasound assisted extraction (EUAE) to simultaneously maximize the yields of polysaccharides (PSY) and phenolics (TPC) from mangosteen (Garcinia mangostana L.) peels with the aid of Box-Behnken design. The chemical structure of the polysaccharides and the bioactive activities of the phenolics extracted by two methods were also determined and compared. At the optimal conditions, the results revealed that UMAE produced a less amount of polysaccharides (18.4%) but required a shorter total treatment time (66 min) than EUAE. In contrast, EUAE generated much higher PSY (32.86%) and had an additional advantage of using the medium with less acidity (pH 4.7 as compared with pH 2). Both approaches resulted to a quite equivalent amount of phenolics (104–111 mg gallic acid equivalent per g dry weight). The FTIR spectra explored that the UMAE polysaccharides had a similar chemical structure with commercial pectin while the EUAE ones had distinguished peaks, appropriately related to the complex network structure of rhamnogalacturonan, homogalacturonan and polygalacturonic acid. On the other hand, both UMAE and EMAE phenolic extracts had similarly high inhibitory effect against α-glucosidase with their IC50 of 1.16–1.18 mg/mL. However, the EMAE phenolic extract had nearly doubled 2, 2-diphenyl-1-1-picrylhydrazyl (DPPH) scavenging activity (4080 μg TE/mL extract) as compared to the UMAE one. These findings conclude that polysaccharides and polyphenols from both extraction methods could be used as ingredients for nutraceutical products and food processing with desirable characteristics. [ABSTRACT FROM AUTHOR]

Drying conditions significantly impact the compositions and microstructures of polysaccharides, leading to various effects on their chemical characteristics and bioactivities. The objective of this study was to investigate how different industrial drying techniques, i.e., hot air drying, infrared drying, microwave vacuum drying, and freeze drying, affect the structural properties and biological activities of polysaccharides extracted from Rosa roxburghii Tratt fruit (RRTP). Results revealed that these drying methods significantly altered the extraction yield, molecular weights, monosaccharide ratios, contents of uronic acid and total sugars, gelling properties, particle sizes, thermal stability, and microstructures of RRTPs. However, the monosaccharide composition and functional groups of polysaccharides remained consistent across the different drying techniques. Biological activity assays demonstrated that RRTPs, particularly those processed through microwave vacuum drying (MVD-RRTP), exhibited excellent anti-linoleic acid oxidation, robust anti-glycosylation effects, and significant α-glucosidase inhibition in vitro. The outcomes of this research demonstrate that microwave vacuum drying serves as an effective pre-extraction drying method for RRTPs, enhancing their biological activities. This technique is particularly advantageous for preparing RRTPs intended for use in functional foods and pharmaceuticals, optimizing their health-promoting properties for industrial applications. [ABSTRACT FROM AUTHOR]

Objectives: The aim is to discover α-glucosidase/acetylcholinesterase inhibitors as lead compounds from a traditional herbal prescription of Qi-Li-Qiang-Xin capsule (QLQX). Methods: A novel strategy combining time-based fractionation, LC-QTOF-MS, enzymatic activity assay, molecular docking and component-target association analysis was performed to discover α-glucosidase/acetylcholinesterase inhibitors from QLQX. Time-based fractionation combined with enzymatic activity assay was used to find the distribution period of active compounds in the herbal prescription. LC-QTOF-MS was used to analyze the structure of active compounds. Molecular docking was applied to explore the interaction between active compounds and targets. Results: According to time-based fractionation, the active components of QLQX for acetylcholinesterase were primarily concentrated in the highly polar region, whereas the active components for α-glucosidase were predominantly found in the moderately polar area. A total of 33 compounds were identified by comparing with chemical reference substances. Dihydrotanshinone Ⅰ (16.98 µM), hydroxysafflor yellow A (84.57 µM), salvianolic acid A (76.62 µM) and cryptotanshinone (112.68 µM) were identified as acetylcholinesterase inhibitors from QLQX. Similarly, rosmarinic acid (62.29 µM), isochlorogenic acid A (17.95 µM), 4,5-dicaffeoylquinic acid (117.93 µM), danshensu (207.88 µM), salvianolic acid A (1.31 µM), 3,4-dicaffeoylquinic acid (91.71 µM), formononetin (67.26 µM), ginsenoside Rd (3.43 µM), ginsenoside Rb1 (26.37 µM) and ginsenoside F1 (18.79 µM) were discovered as α-glucosidase inhibitors. Notably, salvianolic acid A inhibited both acetylcholinesterase and α-glucosidase. The results of molecular docking indicated that hydrogen bonds, hydrophobic interactions and Pi-Pi T-shaped interactions were crucial for inhibiting acetylcholinesterase. Meanwhile, hydrogen bonds, hydrophobic interactions and Pi-Pi stacked interactions were significant in suppressing α-glucosidase. Conclusion: QLQX contains numerous acetylcholinesterase and α-glucosidase inhibitors, demonstrating its potential therapeutic benefits for Alzheimer's disease and diabetes. [ABSTRACT FROM AUTHOR]

Objective: Aruncus dioicus has been known by the scientific literature and folk experiences for its diverse biological activities, including anti-hyperglycemic effects. Methodology: The aerial parts of the plant collected from Quan Lan Island (Vietnam) were subjected to a methodical theory-experiment investigation for its chemical composition and biological potentials. Results: Firstly, experimental isolation and spectroscopic characterization identified the compositional compounds, ie sambunigrin (1), prunasin (2), uridine (3), and adenosine (4). Secondly, their elucidated structures were predicted with promising bio-chemo-pharmacological potentiality by different computational platforms, ie: docking simulation (docking scores < 10 kcal.mol−1); quantum calculation (dipole moments < 3 Debye); QSARIS model (satisfying Lipinski's rule of five); SwissADME model (satisfying Pires’ interpretations). Finally, the compounds (1-4) were under accumulative purification and in vitro tests against diabetes-related enzymes, ie: protein tyrosine phosphatase 1B (1 with lowest IC50 value 0.39 ± 0.26 μM, 2 with no activity) and α-glucosidase (1 with lowest IC50 value 44.89 ± 0.93 μM, 2 with no activity); also, the inhibitory kinetics based on Lineweaver-Burk and Dixon plot experiments revealed the competitive inhibition mode of 1 against PTP1B (Ki value 0.49 μM). Conclusions: Altogether, the results obtained suggest that A. dioicus and its bioactive compounds, especially sambunigrin (1), uridine (3), and adenosine (4), could be considered as a natural source for further research and development of anti-diabetic agents. [ABSTRACT FROM AUTHOR]

Starch is the main source of energy for the human body. Natural products such as procyanidin (PC) and protocatechuic acid (PCA) can reduce postp'ran'dial blood sugar by controlling the digestion of starch. The inhibition effects of PC and PCA on α-amylase and α-glucosidase were studied using inhibition rate determination, Lineweaver-Burk double reciprocal diagram, ultraviolet spectroscopy, fluorescence quenching, equivalent mapping, and Fourier transform infrared spectroscopy. The results showed that the IC50 values of PC for α-amylase and α-glucosidase inhibition were 0.0524 and 0.0106 mg/mL, respectively, and those of PCA were 1.9426 and 1.0667 mg/mL respectively, which showed that PCA had better inhibition ability. The Lineweaver-Burk double reciprocal diagram showed that the inhibition of PC and PCA on α-amylase was a mixed inhibition, and the inhibition on α-glucosidase was non-competitive inhibition and competitive inhibition, respectively. The Binding of PC and PCA with α-amylase and α-glucosidase mainly depended on hydrophobic and hydrogen bonds, and further altered the enzyme structure by changing the microenvironment of amino acid residues. The inhibitory effects on α-glucosidase were the best when the ratio of PC and PCA was 1:21, and the inhibitory effects on α-amylase were optimal at 1:37. When the ratio of PC and PCA was 1:21, CI was less than 1, which showed a synergistic inhibitory effect on α-glucosidase. When the compounding ratio was 1:37, CI was less than 1, which showed a synergistic inhibitory effect on α-amylase. This study revealed the inhibitory mechanism of the combined use of PC and PCA on starch-digesting enzymes and would provide a theoretical basis for the development of natural hypoglycemic dietary supplements as health food excipients or drugs.

Panose is iso-malto-oligosaccharide contained α-1,6 glycosidic bonds, and α-glucosidase is the key enzyme to produce panose. In this study, the α-glucosidase gene in deep-sea hydrothermal vents thermophilic archaea Thermococcus siculi HJ21 was synthesized, and cloned into the vector pET29a. Then expressed in Escherichia coli BL21 and purified by His Trap HP column. The molecular weight of α-glucosidase was determined by SDS-PAGE. The enzymatic properties and transglycosylation were also investigated. The results showed that the gene of α-glucosidase was 729 bp and encoded 242 amino acids. The molecular weight of α-glucosidase was about 27.2 kDa. Its optimal temperature and pH were 40 ℃ and 6.0 respectively. When the receptor was fructose, and the ratio of fructose and maltose was 1:9, the highest yield of panose could reached 79.1% after 10 h reaction. The results provide a basis for producing high-purity panose by α-glucosidase from archaea.

Abstract Background Mucuna pruriens var. utilis (Wall. ex Wight) belonging to the family Fabaceae. Renowned for its diverse array of phytochemicals, this plant has been historically employed in the treatment of various ailments. The objectives of this study are to evaluate the anti-diabetic, anti-inflammatory, and antioxidant properties of the optimized M. pruriens var. utilis seed extract. Methods The in-vitro anti-inflammatory activity of M. pruriens var. utilis ethanolic extracts was scrutinized using the Human Red Blood Cell (HRBC) method. To evaluate antioxidant activity, ABTS and DPPH assays were employed. Furthermore, the antidiabetic activity was assessed through α-amylase and α-glucosidase inhibition assays. Results In the ethanolic extract of M. pruriens var. utilis numerous phytoconstituents were found by doing a phytochemical analysis (alkaloids, flavonoids, phenols, saponins, steroids, glycosides, tannins). The total phenolic and flavonoid content were determined to be 112.07 ± 1.21 mg of gallic acid equivalents GAE/g and 101.41 ± 1.08 mg of quercetin equivalents QE/g respectively. In this investigation ethanolic extract of M. pruriens var. utilis exhibited a high anti-inflammatory, antioxidant and antidiabetic activities in a dose-dependent manner. The M. pruriens var. utilis extract shows that anti-inflammatory activity 32.26 ± 3.23%, potent antioxidant effect by ABTS radical scavenging assay IC50 67.46 ± 1.45 µg/mL and DPPH radical scavenging assay IC50 63.34 ± 2.27 µg/mL and in addition, showed promising antidiabetic potential by inhibiting α-amylase IC50 33.42 ± 1.35 µg/mL and α-glucosidase IC50 28.34 ± 1.41 µg/mL. Conclusion These findings provide additional support for the traditional medicinal use of M. pruriens var. utilis in treating inflammation, oxidative stress, and diabetes mellitus.

Abstract In this work, we have reported the design, synthesis, in vitro, and in silico enzymatic evaluation of new bis-4-hydroxycoumarin-based phenoxy-1,2,3-triazole-N-phenylacetamide derivatives 5a-m as potent α-glucosidase inhibitors. All the synthesized analogues showed high inhibition effects against α-glucosidase (IC50 values ranging between 6.0 ± 0.2 and 85.4 ± 2.3 µM) as compared to the positive control acarbose (IC50 = 750.0 ± 0.6 µM). Among the newly synthesized compounds 5a-m, 2,4-dichloro-N-phenylacetamide derivative 5i with inhibition effect around 125-folds more than the acarbose was identified as the most potent entry. A structure–activity relationship (SAR) study about the title compounds 5a-m demonstrated that the inhibition effects of these compounds depend on the pattern of substitution on the N-phenylacetamide ring. The interaction modes and binding energies in the active site of enzyme of the important analogues (in term of SAR study) were evaluated through molecular docking study. Molecular dynamics and prediction of pharmacokinetic properties and toxicity of the most potent compound 5i also evaluated and the obtained data was compared with the acarbose.

Abstract Underutilised legumes are important crop species whose cultivation and consumption are declining despite their medicinal and nutritional benefits. One of the most pressing global health concerns of the twenty-first century is diabetes, characterised by elevated blood sugar levels (hyperglycaemia). Food plays a huge role in the incidence and management of metabolic diseases such as diabetes. Hence, pharmacological research along the food-medicine continuum is being ignited by recent evidence linking diet to health and illness incidence. Herein, we determined in vitro the inhibitory effects of the gene bank-stored seed and freshly cultivated seed and leaf extracts of ten accessions of an underutilised legume (Macrotyloma geocarpum) on the enzymes involved in carbohydrate breakdown to glucose (α-amylase and α-glucosidase) as a strategy to reduce hyperglycaemia. The extracts of seed accessions obtained from the gene bank showed weakly α-amylase inhibition (IC50 range = 300–1000 µg/mL) while, extracts of the cultivated seed accessions generally showed enhanced inhibitory effects (IC50 range = 63–355 µg/mL), when compared to standard Acarbose® (IC50 = 64.23 ± 0.02 µg/mL). Freshly harvested seed accessions (72–616 µg/mL) were also observed to have enhanced inhibitory effects on α-glucosidase enzyme than the seeds from the gene bank (39–185 µg/mL) when compared to Acarbose® (73.23 ± 0.02 µg/mL). However, the leaf extracts of the cultivated accessions displayed significantly higher α–amylase inhibition (IC50 range = 54–61 µg/mL) than the cultivated seeds while a reversed case was observed in the α–glucosidase inhibition. Overall, this study suggests the medicinal importance of the underutilised M. geocarpum legume in the management of diabetes while considering the varying bioactive effects of the accessions as well as cultivation and storage.

Tiara Ramadaini,&ast; Sri Adi Sumiwi,&ast; Ellin Febrina&ast; Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Padjadjaran University, Jatinangor, Indonesia&ast;These authors contributed equally to this workCorrespondence: Sri Adi Sumiwi, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy Padjadjaran University, Jl. Raya Sumedang KM 21, Jatinangor, West Java, 45363, Indonesia, Email sri.adi@unpad.ac.idBackground: Diabetes mellitus is a complex metabolic disorder that has an enormous impact on people’s quality of life and health. Although there is no doubt about the effectiveness of oral hypoglycemic agents combined with lifestyle management in controlling diabetes, no individual has ever been reported to have been completely cured of the disease. Globally, many medicinal plants have been used for the management of diabetes in various traditional systems of medicine. A deep look in the literature has revealed that the Liliaceae family have been poorly investigated for their antidiabetic activity and phytochemical studies. In this review, we summarize medicinal plants of Liliaceae utilized in the management of type II diabetes mellitus (T2DM) by inhibition of α-glucosidase enzyme and phytochemical content.Methods: The literature search was conducted using databases including PubMed, ScienceDirect, and Google Scholar to find the significant published articles about Liliaceae plants utilized in the prevention and treatment of antidiabetics. Data were filtered to the publication period from 2013 to 2023, free full text and only English articles were included. The keywords were Liliaceae OR Alliaceae OR Amaryllidaceae AND Antidiabetic OR α-glucosidase.Results: Six medicinal plants such as Allium ascalonicum, Allium cepa, Allium sativum, Aloe ferox, Anemarrhena asphodeloides, and Eremurus himalaicus are summarized. Phytochemical and α-glucosidase enzymes inhibition by in vitro, in vivo, and human studies are reported.Conclusion: Plants of Liliaceae are potential as medicine herbs to regulating PPHG and prevent the progression of T2DM and its complication. In silico study, clinical application, and toxicity evaluation are needed to be investigated in the future.Keywords: Liliaceae, antidiabetic, phytochemicals, α-glucosidase, traditional medicine

Vetiveria zizanioides, known as vetiver grass, is renowned for its ecological significance in soil erosion control and the restoration of lands polluted by heavy metals. Additionally, this plant is extensively harvested for vetiver oil, widely utilized in both medicine and perfumery. The study was designed to investigate the phytochemicals, antilipase, hemoglobin antiglycation, antihyperglycemic, antifungal, and antibacterial properties of V. zizanioides. The GC-MS analysis revealed the presence of various volatile compounds, among which the most predominant ones, which are, 4,6,6-Trimethyl-2-(3-methylbuta-1,3-dienyl) −3-oxatricyclo [5.1.0.0(2,4)] octane, Cycloisolongifolene (8,9-dehydro-), and 9 H-Cycloisolongifolene (8-oxo-). It is noteworthy that this essential oil has shown significant inhibitory activity against α-amylase, α-glucosidase, pancreatic lipase, and glycation, with respective IC50 values of 0.47 ± 0.01, 0.42 ± 0.004, 0.58 ± 0.008, and 0.49 ± 0.005 mg/mL. Additionally, the antimicrobial activity of EoVZ was assessed against a diverse spectrum of Gram+ and Gram- bacteria, as well as fungi, using both disc-diffusion and broth-microdilution techniques. The results showed significant antimicrobial effects against all tested microorganisms, with inhibition zones ranging from 28.33 ± 1.66 mm to 9.0 ± 0.0 mm for bacteria and from 22.5 ± 1.7 mm to 14.0 ± 0.3 mm for fungi. Moreover, minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC), and minimum fungicidal concentrations (MFC) were determined, with values ranging from 0.0625% to 2.0% (v/v) for bacteria and from 2.0% to 8.0% (v/v) for fungi. The MBC/MIC and MFC/MIC ratios indicated bactericidal and fungicidal mechanisms. This study underscores the prominent attributes of EoVZ, particularly its antimicrobial and antidiabetic properties, suggesting its potential as a natural and effective agent ensuring high safety standards for public health.

Artificial Intelligence is transforming drug discovery, particularly in the hit identification phase of therapeutic compounds. One tool that has been instrumental in this transformation is Quantitative Structure-Activity Relationship (QSAR) analysis. This computer-aided drug design tool uses machine learning to predict the biological activity of new compounds based on the numerical representation of chemical structures against various biological targets. With diabetes mellitus becoming a significant health challenge in recent times, there is intense research interest in modulating antidiabetic drug targets. α-Glucosidase is an antidiabetic target that has gained attention due to its ability to suppress postprandial hyperglycaemia, a key contributor to diabetic complications. This review explored a detailed approach to developing QSAR models, focusing on strategies for generating input variables (molecular descriptors) and computational approaches ranging from classical machine learning algorithms to modern deep learning algorithms. We also highlighted studies that have used these approaches to develop predictive models for α-glucosidase inhibitors to modulate this critical antidiabetic drug target.

Một trong những cách giúp giảm lượng hấp thu glucose vào máu trong điều trị bệnh đái tháo đường là ức chế enzyme α-glucosidase. Sauropus androgynus (L.) Merr. chứa nhiều thành phần có hoạt tính sinh học có tiềm năng trong chống oxy hóa và hỗ trợ điều trị bệnh đái tháo đường. Bài báo khảo sát tác dụng chống oxy hóa bằng mô hình khử gốc tự do DPPH và khả năng ức chế enzyme α-glucosidase của lá Sauropus androgynus (L.) Merr. bằng phản ứng phân cắt cơ chất pNG in vitro. Kết quả cho thấy, lá Sauropus androgynus (L.) Merr. có tác dụng chống oxy hóa với EC50>256 mg/mL, so sánh chất chuẩn tham khảo quercetin EC50=9,97 ± 0,25 mg/mL và tác động ức chế α-glucosidase với IC50=10,91 ± 0,21µg/mL so sánh chất chuẩn acarbose IC50=134,56 ± 3,02 µg/mL. Tiềm năng tác dụng oxy hóa và khả năng ức chế enzyme α-glucosidase của Sauropus androgynus (L.) Merr. cần được tiếp tục nghiên cứu ứng dụng trong thực phẩm chức năng và thuốc.

Plants represent a great source of medicines, and for their components to be discovered, extraction processes must be developed, especially methods based on green technology. Supercritical fluid extraction (SFE) was employed as a green method for Moringa oleifera extraction in the present investigation. The maximum yield of extraction was obtained at 25 MPa. Moreover, the extraction at 25 MPa induced the release of various phenols and flavonoids, as analyzed via high-performance liquid chromatography. The investigation revealed the concentrations of chlorogenic, gallic, rosmarinic, and coumaric acids to be 150.59, 89.90, 44.75, and 29.41 µg/mL, respectively at 25 MPa. However, their concentrations were 0.73, 1.53, 0.24, and 0.04 µg/mL, respectively at 15 MPa; vs. 4.73, 2.62, 1.06, and 0.50 at 35 MPa, respectively. Totals of saponin, flavonoid, phenolic, tannins, and alkaloid were recorded in maximum yield at 25 MPa. Moringa oleifera extracted at 35 MPa reflected highest inhibition zones of 27 ± 0.1, 30 ± 0.2, and 30 ± 0.1 mm against C. glabrata, C. tropicalis, and C. albicans, correspondingly. α-Amylase and α-glucosidase activities were greatly suppressed by the M. oleifera extract at 25 MPa with less IC50 (12.97 µg/mL and 6.0 µg/mL), than the IC50 (53.46 and 22.02 µg/mL) at 15 MPa, compared with acarbose IC50 (5.52 and 2.64 µg/mL), correspondingly.

Abstract Α-glucosidase inhibition can be useful in the management of carbohydrate-related diseases, especially type 2 diabetes mellitus. Therefore, in this study, a new series of 6-chloro-2-methoxyacridine bearing different aryl triazole derivatives were designed, synthesized, and evaluated as potent α-glucosidase inhibitors. The most potent derivative in this group was 7h bearing para-fluorine with IC50 values of 98.0 ± 0.3 µM compared with standard drug acarbose (IC50 value = 750.0 ± 10.5 μM). A kinetic study of compound 7h revealed that it is a competitive inhibitor against α-glucosidase. Molecular dynamic simulations of the most potent derivative were also executed and indicated suitable interactions with residues of the enzyme which rationalized the in vitro results.

Starch was the main source of carbohydrates in people's daily diet, and its digestibility was an important factor affecting the body's postprandial blood glucose level. In this paper, the effect of xylose on the in vitro digestive properties of corn starch and its mechanism of action were investigated. The in vitro digestibility of starch was evaluated by an in vitro simulated digestion system after different additions of xylose (5%, 10%, and 15%), and the mechanisms of xylose on α-amylase and α-glucosidase, as well as its effect on blood glucose fluctuation through enzyme inhibition kinetics, molecular docking, and human glycemic index (GI) tests. The results showed that the digestive hydrolysis of corn starch was inhibited by different amounts of xylose, and the IC50 values of xylose on α-glucosidase and α-amylase were 205.35 and 4.75 mg/mL, respectively, which belonged to the mixed type inhibitors. Xylose interacted with amino acid residues of α-glucosidase and α-amylase through hydrogen bonding with binding energies of −3.05 and −5.30 kcal/mol, respectively. Additionally, the GI value of plant-based peptidoglycan milk decreased from 58 to 45 after the addition of xylose, which demonstrated that xylose was effective in decreasing the fluctuation of postprandial blood glucose. The results could provide scientific data to support the research and application of xylose in nutritional and health foods.

This study aspires to evaluate the antibacterial and inhibitory effects of carbohydrate digestive enzymes in tree leaves that are widely distributed in the Mediterranean region. Leaves were sequentially extracted with solvents of increasing polarity. The results demonstrated a wide range of phenolic (3.5–770.7 mg gallic acid equivalent g−1) and flavonoid (0.2–321.3 mg catechin equivalent g−1) contents in leaf extracts. The minimum inhibitory and bactericidal concentration of leaf extracts was determined for six bacteria using the broth microdilution method. The polar extracts of carob, lentisk, and white mulberry leaves exerted strong antibacterial potency against Gram-positive bacteria, while the susceptibility of Escherichia coli on relative apolar extracts of carob, fig, and olive leaves was also observed. In parallel, the inhibitory effects of leaf extracts on carbohydrate digestive enzymes were evaluated. A robust inhibition of α-glucosidase was found for carob and lentisk leaf extracts, followed by extracts produced by white mulberry and olive leaves. Carob and lentisk leaves also act as a-amylase inhibitors at high concentrations. Overall, this study provides valuable data for the nutraceutical value of the “forgotten” treasure of Mediterranean tree leaves and assesses these plants as potential sources of antibacterial and carbohydrate digestive enzyme inhibitory agents for drug discovery.

Abstract Biofilm-associated candidiasis poses a significant challenge in clinical settings due to the limited effectiveness of existing antifungal treatments. The challenges include increased pathogen virulence, multi-drug resistance, and inadequate penetration of antimicrobials into biofilm structures. One potential solution to this problem involves the development of novel drugs that can modulate fungal virulence and biofilm formation, which is essential for pathogenesis. Resistance in Candida albicans is initiated by morphological changes from yeast to hyphal form. This transition triggers a series of events such as cell wall elongation, increased adhesion, invasion of host tissues, pathogenicity, biofilm formation, and the initiation of an immune response. The cell wall is a critical interface for interactions with host cells, primarily through various cell wall proteins, particularly mannoproteins. Thus, cell wall proteins and enzymes are considered potential antifungal targets. In this regard, we explored α-glucosidase as our potential target which plays a crucial role in processing mannoproteins. Previous studies have shown that inhibition of α-glucosidase leads to defects in cell wall integrity, reduced adhesion, diminished secretion of hydrolytic enzymes, alterations in immune recognition, and reduced pathogenicity. Since α-glucosidase, primarily converts carbohydrates, our study focuses on FDA-approved carbohydrate mimic drugs (Glycomimetics) with well-documented applications in various biological contexts. Through virtual screening of 114 FDA-approved carbohydrate-based drugs, a pseudo-sugar Acarbose, emerged as a top hit. Acarbose is known for its pharmacological potential in managing type 2 diabetes mellitus by targeting α-glucosidase. Our preliminary investigations indicate that Acarbose effectively inhibits C. albicans biofilm formation, reduces virulence, impairs morphological switching, and hinders the adhesion and invasion of host cells, all at very low concentrations in the nanomolar range. Furthermore, transcriptomic analysis reveals the mechanism of action of Acarbose, highlighting its role in targeting α-glucosidase.

Highland barley is a unique cereal in the Qinghai-Tibet Plateau of China, and has good effects on improving blood glucose metabolism. However, its specific hypoglycemic ingredients and compatibility are not yet clear. In this manuscript, the polyphenols, polysaccharides, and peptides in whole grain highland barley (WHB) were extracted. And the α-glucosidase inhibitory activity of 3 key active ingredients components and their interaction were investigated. The optimal reaction system for measuring α-glucosidase inhibitory activity using the microplate method was first determined through single factor experiments and Box-Benhnken response surface optimization experiments, i.e., 0.5 U/mL of enzyme concentration, 80 mmol/L of buffer concentration, and 5 mmol/L of substrate concentration. The results showed that all 3 WHB extracts exhibited good α-glucosidase inhibitory activity, with WHB polyphenols having the strongest inhibitory activity. Its inhibition rate reached 83.63% ± 2.92%, corresponding to an IC50 of 0.18 mg/mL. In addition, any 2 hypoglycemic ingredients combinations of the 3 WHB extracts had a certain synergistic effect. Our results will provide guidance for dietary choices in blood glucose control populations and new evidence for the development of functional foods.

The evaluation of in vitro and in silico anti-diabetic activity of wild edible fruit Ziziphus oenophilia (L.) extract: molecular docking and statistical analysis.

To understand the effects of natural fermentation on the changes of phenolic substances in Citrus microcarpa and the inhibition of digestive enzymes, the changes of soluble total phenol, total flavone, α-amylase, α-glucosidase, and pancreatic lipase inhibition rates before and after fermentation were measured. The types of phenolic substances before and after fermentation were identified by UPLC-Q Exactive Orbitrap-MS, and the differential metabolites and their enrichment pathways were screened. Finally, the correlation relationships between the different phenolic metabolites and the inhibitory activities of the above digestion-related enzymes were analyzed based on the correlation coefficient. The results showed that natural fermentation could increase the contents of soluble total phenol and total flavone by 9.20% and 23.68%, respectively, and increase the inhibition rates of α-amylase, α-glucosidase and pancreatic lipase from 11.90% to 28.50%. A total of 52 phenolic substances were detected in Citrus microcarpa. Fermentation did not change the types of phenolic substances, but it significantly increased nine phenolic substances such as nobiletin, caffeic acid, and vitexin, and significantly decreased methoxsarin (P

Context: Scientific verification of the anti-hyperglycemic potential of Kayu sarampa (Xylocarpus moluccensis), which is popularly used for diabetic medication in North Sulawesi, Indonesia, is strongly important to conduct to avoid inappropriate medication that might cause worse conditions. Aims: To investigate the anti-hyperglycemic potential of X. moluccensis stem bark ethyl acetate extract and isolated compounds through the α-glucosidase enzyme inhibitory and antioxidant capacity determination. Methods: The active compound was isolated from ethyl acetate extract of X. moluccensis stem bark. The structures of those compounds were elucidated by infrared spectroscopy, liquid chromatography–mass spectrometry, and nuclear magnetic resonance spectroscopies. To discover the anti-hyperglycemic potency, α-glucosidase enzyme inhibition assay, antioxidant assay (DPPH and FRAP), and in silico study were performed. Results: Three isolated compounds were obtained and characterized as two tetrahydroxyterpenoids compounds, namely xyloccensin E (1) and ruageanin D (2), and one flavonoid compound, namely 3,5,7,3ʹ,4ʹ-pentahidroxyflavan (catechin) (3). Compounds 1 and 3 inhibited the α-glucosidase enzyme with IC50 values of 118.60 and 55.19 µg/mL, respectively, with a competitive inhibition mechanism. This is also in line with in silico findings, and both compounds showed good binding affinity of α-glucosidase protein, which indicated their anti-hyperglycemic activity potential by inhibiting α-glucosidase enzyme. Moreover, compounds 1 and 3 showed antioxidant capacity through the DPPH method with an IC50 value of 54.69 and 2.87 µg/mL. In addition, 100 µg/mL of compounds 1 and 3 also exhibited antioxidant capacity through the FRAP method with values of 66.35 and 213.82 µmol Fe2+/g, respectively. Conclusions: The X. moluccensis stem bark ethyl acetate extract, and isolated compounds exhibit α-glucosidase enzyme inhibitory activity and antioxidant capacity, which confirms its potency as an alternative medication for hyperglycemia issues.