Search Results (167)

Medlar (Mespilus germanica L.) fruit presents a good source of bioactive compounds. This study aimed to optimize the traditional extraction method, maceration, in order to obtain extracts rich in polyphenols. The total phenolic compounds (TPC) from physiologically ripe (PRMFs) and consumable ripe (CRMFs) medlar fruits were extracted to develop models with high accuracy and prediction capacity by response surface methodology (RSM). Furthermore, the main phenolic compounds in the extracts were quantified using HPLC, and the extracts were tested for antioxidant activity and hypoglycemic activity. The extracts were prepared according to a central composite design. The extraction parameters for both PRMFs and CRMFs were time (30–210 min), ethanol concentration (20–80%) and solid-to-solvent ratio (1:10–1:50). The obtained results indicated that the optimal conditions for the extraction were 210 min, 66.55% ethanol, and 1:50 solid-to-solvent ratio (PRMF), and 120 min, 74.96% ethanol, and 1:50 solid-to-solvent ratio (CRMF). Under the optimized conditions, values for TPC were in agreement with the values predicted by RSM. Isoquercitrin, rutin, procyanidin B2, chlorogenic acid and caffeic acid were the most abundant compounds in both PRMF and CRMF optimized extracts. TPC, antioxidant activity, and inhibition of α-glucosidase and α-amylase enzymes did not show significant differences (p > 0.05) among PRMF and CRMF extracts. Full article

To address the limited functional diversity of traditional kombucha, this study utilized red yeast rice (RYR) as an alternative substrate and prepared three samples: black tea kombucha (KBT), black tea-red yeast rice mixed kombucha (KBL, at a 1:1 ratio), and red yeast rice kombucha (KRY). After 9 days of fermentation, KRY exhibited the lowest pH, the highest total acidity, and notable sugar metabolic activity. It exhibited in vitro inhibition rates of 82.8%, 78.2%, 70.3%, and 76.9% against cholesterol esterase, pancreatic lipase, α-glucosidase, and α-amylase, respectively, indicating potential hypoglycemic and hypolipidemic activities. In contrast, KBT maintained the strongest antioxidant capacity, with scavenging rates exceeding 90% against both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-Azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS). A total of 72 volatile flavor compounds (VFCs) were identified, with 7 key compounds enriched in KRY, which enhanced its sensory acceptance and received the highest scores in color, clarity, and aroma. Microbial community analysis revealed the post-fermentation dominance of Komagataeibacter, Acetobacter, and Saccharomyces, which correlated positively with key VFCs. These findings indicate that RYR as a substrate enhances functional microbial growth, sugar metabolism, organic acid production, flavor enrichment, and in vitro inhibitory activity of enzymes associated with hypoglycemic and hypolipidemic effects. Full article

Type 2 diabetes mellitus (T2DM) is a globally prevalent chronic metabolic disorder that poses severe public health risks. Synthetic hypoglycemic agents are susceptible to inducing adverse reactions, thus driving the development of natural, safe and highly effective plant-derived hypoglycemic active compounds as a research hotspot. Inhibiting the activity of α-glucosidase and α-amylase represents an effective strategy to regulate postprandial blood glucose levels. This study investigated the synergistic hypoglycemic activity of a composite (PS-PP) formed by polysaccharide (PS) and polyphenols (PP) from Ziziphus jujuba Mill. cv. Muzao and elucidated the structural basis underlying this synergistic effect. First, MPS and MPP were isolated and purified, followed by the in vitro assembly to prepare PS-PP. The hypoglycemic activities of MPS, MPP and MPS-PP were evaluated via in vitro enzyme inhibition assays, while structural characterization was conducted using GPC-MALLS, FT-IR and SEM techniques. Results demonstrated that PS-PP exerted the strongest activity under optimal conditions (0.75 mg/mL concentration, pH 4.0, 1:2 mass ratio), with IC₅₀ values of 1.14 μg/mL and 0.82 μg/mL against the two enzymes, which were superior to those of polysaccharides (15.10 and 36.06 μg/mL) and polyphenols (1.18 and 46.24 μg/mL). Structural analysis revealed that the interaction between PS and PP was primarily mediated by hydrogen bonds. PS-PP exhibited significant differences from single-component compounds in molecular weight distribution, functional group binding and surface morphology. These structural alterations were identified as the key factors contributing to its enhanced hypoglycemic efficacy. This study clarifies the synergistic hypoglycemic mechanism of MPP-PS and lays a scientific foundation for the development of natural hypoglycemic preparations and functional foods. Full article

(1) Background: Diabetes mellitus is a chronic metabolic disease with a rising global prevalence. Mulberry leaf (ML), a traditional medicinal and edible plant, possesses notable hypoglycemic effects and has a long history of usage. This review aims to systematically consolidate the research progress on the hypoglycemic constituents derived from ML, including their chemical structure, extraction methods, quality analysis techniques, and hypoglycemic mechanisms. (2) Methods: Adhering to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines, a comprehensive literature search was conducted using Web of Science and PubMed databases to find relevant studies published between 2015 and 2025. (3) Results: This review evaluates both conventional and modern techniques such as water extraction, ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and enzyme-assisted extraction (EAE), highlighting their advantages and limitations when applied on ML. Additionally, this review examines the analytical techniques applied in the quality control of ML and its constituents. This is complemented by a summary of hypoglycemic mechanisms, focusing on the inhibition of oxidative stress, amelioration of insulin resistance, regulation of related enzyme activity, and modulation of gut microbiota. (4) Conclusions: ML demonstrates considerable potential for treating diabetes. However, further studies are needed for new drug discovery based on new ML-derived bioactive constituents, highly efficient extraction methods, quality analysis techniques, and underlying mechanisms. Full article

The treatment of diabetes in the modern era, with its growing patient population, represents a significant challenge due to the wide range of adverse effects associated with medications that target complex biochemical processes. Consequently, researchers are investigating the hypoglycemic potential of existing drugs. Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain, fever, and various inflammatory conditions. Recent studies have shown that NSAIDs, particularly salicylates, can influence glycemia through multiple mechanisms, including inhibition of gastrointestinal enzymes, blockade of K_ATP channels, activation of AMP-activated protein kinase (AMPK), and inhibition of NF-κB signaling, among others. Accordingly, this review explores the hypoglycemic potential of NSAIDs as well as their derivatives, and the diverse mechanisms through which these molecules may influence glucose homeostasis. Full article

Background: This study aimed to explore the synergistic hypoglycemic effect and mechanism of 1-deoxynojirimycin (DNJ) in mulberry leaves and theaflavins (TFs) in black tea. Methods: The synergistic inhibition of α-glucosidase and α-amylase by DNJ-TFs was evaluated using enzyme assays and the Chou–Talalay model. Insulin-resistant (IR) HepG2 cells and high-fat diet (HFD)-induced type 2 diabetes mellitus mice were treated with DNJ, TFs, or DNJ-TFs, determining the efficacy of drug combinations by measuring glycolipids and inflammatory factors. Network pharmacology and molecular docking were used to identify key target genes and signaling pathways, and CETSA experiments were used to verify the binding of drugs to targets. Key genes were further verified by immunofluorescence, Western blot, and Real-time PCR. Results: DNJ-TFs synergistically suppressed α-glucosidase (CI = 0.85) and α-amylase (CI = 0.76). In HepG2 cells, DNJ-TFs ameliorated palmitic acid-induced IR by promoting glucose uptake, attenuating lipid accumulation, and regulating glycolipid metabolism. In HFD mice, DNJ-TFs counteracted hyperglycemia, dyslipidemia, systemic inflammation and oxidative stress, elevated HOMA-IR, and hepatic steatosis. Network pharmacology integrated with experimental validation identified PTGS2 and MMP9 as key binding targets of DNJ and TFs. Furthermore, DNJ-TFs could inhibit the increase in liver TNFα protein and the decrease in p-AKT, p-GSKα, p-GSKβ, and GLUT2 protein caused by high fat, both in vivo and in vitro. Conclusions: DNJ and TFs exert synergistic glucose-lowering effects by targeting PTGS2/MMP9 and regulating the TNFα/AKT/GSK3/GLUT2 axis, providing a promising natural therapeutic strategy for diabetes management. Full article

Background: Two natural steroids derived from cholesterol pathways are testosterone and progesterone, androgen and antiandrogen receptor binding. Steroid androgen antagonists can be prescribed to treat an array of diseases and disorders such as gender dysphoria. In men, androgen antagonists are frequently used to treat prostate cancer and hyperplasia. Sex hormones regulate the expression of the viral receptors in COVID-19 progression, and these hormones may act as a metabolic signal-mediating response to changes in glucose and Reactive Oxygen Species (ROS). The objective of the present study is to use artificial intelligence (AI) applications in healthcare to predict the targets and to assess biological assays of novel steroid derivatives prepared in house from the commercially available 16-dehydropregnenolone acetate (DPA^®) aimed at achieving the metabolic stability of glucose and steroid brain homeostasis. This suggests the introduction of aromatic or aliphatic structures in the steroid B-ring and D-ring. This is important since the roles of 5α-reductase and ROS in brain control of glucose and novel steroids homeostasis remain unclear. Methods: A tool prediction was used as a tuned algorithm, with the novel steroid derivatives data in web interface to carry out their pharmacological evaluation. The new steroidal derivatives were determined with neuroprotection effect using the select biomarkers of oxidative stress on induced hypoglycemic male rat brain and liver. The enzyme kinetics was established by the inhibition of the 5α-reductase enzyme on the brain myelin. Results: We used novel chemical structures to order the information of a Swiss data bank that allow target predictions. Biological assays suggest that steroid derivatives with an electrophilic center can interact more efficiently with the 5α-reductase enzyme, and by this way, induce neuroprotection in hypoglycemia model. All compounds were synthesized with a yield of 30–80% and evaluated with tool target prediction to understand the molecular mechanisms underlying a given phenotype or bioactivity and to rationalize possible favorable or unfavorable side effects, as well as to predict off-targets of known molecules and to clear the way for drug repurposing. Apart, they turned out to be good inhibitors for the 5α-reductase enzyme. Conclusions: The probed efficacy of these novel steroids with respect to spironolactone control appears to be a promising compound for future hormonal therapy with neuroprotection activity in glucose disorder status. However, further research with clinically meaningful endpoints is needed to optimize the use of androgen antagonists in these hormonal therapies in COVID-19 progression. Full article

Background: Conventional insulin injections cannot mimic physiological pancreatic function and often lead to dangerous hypoglycemic events that glucose-responsive systems aim to prevent. Glucose-responsive microneedles (MNs) offer a promising closed-loop alternative. We developed an enzyme-free, glucose-responsive MN patch composed of a PVA/Dextran hydrogel dynamically crosslinked with borax, and evaluated its performance, biosafety, and in vivo efficacy. Methods: MNs were fabricated from PVA/Dextran via micromolding and crosslinked with borax. The formulation was systematically optimized based on mechanical properties and glucose-responsive release kinetics. Physicochemical properties, biosafety (cytotoxicity, skin barrier recovery, boron leaching), and in vivo efficacy in a type 1 diabetic mouse model were evaluated in comparison to a subcutaneous (SC) insulin injection. Results: The optimized MNs showed robust mechanics (per-needle fracture force approximately 1.0 N) for reliable skin penetration. The system demonstrated clear glucose sensitivity, with a release flux ratio ≥1.5 between hyperglycemic (e.g., 400 mg·dL⁻¹) and normoglycemic (100 mg·dL⁻¹) conditions and exhibited excellent reversibility under alternating glucose levels. The patch was highly biocompatible, with >95% cell viability, the only transient skin barrier disruption that fully recovered within 24 h, and had low boron release from patches in vitro. In vivo, the optimized sI-MN patch demonstrated a sustained, glucose-responsive release profile, maintaining blood glucose in diabetic mice near 100 mg·dL⁻¹ for approximately 8 h. This pharmacokinetic profile contrasts markedly with the rapid hypoglycemic nadir and rebound hyperglycemia observed with a standard subcutaneous insulin bolus, highlighting the patch’s potential for mitigating hypoglycemia. Conclusions: The enzyme-free PVA/Dextran/borax MN patch enables autonomous, glucose-responsive insulin delivery. It provides more stable and safer glycemic control than conventional injections by mitigating the risk of hypoglycemia. By mitigating the hypoglycemic risk associated with bolus injections, this systematically optimized platform represents a potential step toward a safer, patient-friendly diabetes therapy, though significant challenges in duration and dose scaling remain. Full article

Type 2 diabetes mellitus remains a major global health challenge, and natural hypoglycemic compounds are of increasing interest. Aqueous extracts from five Brazilian medicinal plants (Lippia origanoides Kunth, Amburana cearensis (Allemão) A.C. Smith, Justicia pectoralis Jacq., Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz, and Spondias mombin L.) were evaluated for α-glucosidase and intestinal disaccharidase inhibition; next, they were chemically profiled by UPLC-HRMS. Extracts of L. origanoides, A. cearensis, and J. pectoralis exhibited the strongest activities, attributed to flavonoids, iridoid and cinnamic acid derivatives, phenolic acids, and saponins. Molecular docking identified hyperoside, eudesmic acid and isoquercitrin as their main α-glucosidase inhibitors, respectively. In vitro testing confirmed that isoquercitrin effectively inhibited α-glucosidase (IC₅₀ = 0.09 mg mL⁻¹), showing stronger activity than acarbose. ADME simulations indicated low gastrointestinal absorption but favorable intestinal enzyme-targeted properties, consistent with their pharmacological profiles. Acute toxicity in zebrafish showed low toxicity for L. origanoides and A. cearensis and moderate levels for J. pectoralis, supporting their overall safety. These findings highlight these species as promising sources of bioactive compounds for developing safe, plant-based antidiabetic agents. Full article

Lycium barbarum L. (abbreviated to L. barbarum), a traditional dual-use plant as food and medicine, contains polysaccharides from Lycium barbarum L. (LBPs) as its key bioactive component. This study aimed to examine the phenotypic characteristics, polysaccharide content, and their correlation with activity across various commercial grades of L. barbarum. Five commercial grades of L. barbarum were selected for analysis to determine their phenotypic characteristics and polysaccharide content. High-performance liquid chromatogram-diode array detection (HPLC-DAD) and ¹H NMR were employed to analyze the monosaccharide composition of LBPs, of which their hypoglycemic activity was further valuated. Results revealed significant differences in fruit weight and diameter among different grades (p < 0.05), while floating rate and bulk density remained unaffected by grades. Variations were observed in the chromaticity coordinates, with the c values showing notable differences (p < 0.01). Polysaccharide content tended to increase with higher grades and smaller fruit sizes, ranging from 1.94% to 5.69%. The polysaccharides in different contained monosaccharides of Man, Rha, Ara, Gal, Glc, GalA, GlcA and Xyl, with Ara and Gal being predominant. Identified through ¹H NMR spectra, the peak intensity of Ara increased from lower to higher grades, and the arrangement of the chemical shifts reflected distinct commercial grade characteristics. The inhibitory concentration (IC₅₀) against α-amylase and α-glucosidase ranged from 0.418 to 1.345 mg/mL, and 0.474 to 1.052 mg/mL, respectively, indicating good hypoglycemic activity within this range. The main monosaccharide groups Ara, Gal, and GalA were identified as key contributors to enzyme inhibition. Collectively interpreting the phenotypic features, polysaccharide content, monosaccharide composition, NMR data and activity profiles, Ara, Gal and GalA emerge as signature monosaccharide components of LBPs. These results provide novel theoretical insights for L. barbarum quality assessment. Full article

Natural deep eutectic solvents (NaDESs) have emerged as green and sustainable alternative solvents for extracting valuable bioactive compounds from agro-industrial by-products. NaDESs are stable, soluble, and biodegradable with low melting points and a wide range of applications. These characteristics align closely with the principles of green chemistry, making NaDESs promising for use in the food industry. Recent studies demonstrate that NaDESs can effectively extract proteins, polysaccharides, polyphenols, carotenoids, alkaloids, and other bioactives from sources such as vegetable waste, cereal by-products, and fruit pomace, often performing better than traditional solvents such as methanol and ethanol. The bioactive components of these extracts may exhibit antioxidant, anti-inflammatory, antihypertensive, anticancer, or antimicrobial activity and can be used as functional ingredients, nutraceuticals, or preservatives. Furthermore, NaDES-derived extracts have been shown to have hypoglycemic effects by inhibiting enzymes involved in the metabolism of carbohydrates and reducing oxidative stress. As a result, they may find use as functional food ingredients in diabetes management. This review presents the recent research on the extraction of bioactive compounds from agro-industrial by-products using NaDESs and an evaluation of their antidiabetic potential. Full article

Boesenbergia rotunda (L.) Mansf., commonly known as fingerroot or “Kra-Chai,” is a traditional Thai medicinal plant used for treating digestive and metabolic disorders. Recent evidence highlights its potential role in controlling hyperglycemia, though its active compounds and mechanisms remain unclear. This study evaluated the antidiabetic activity of B. rotunda crude extract and its major flavonoids, pinostrobin and pinocembrin, through in vitro enzyme inhibition and cellular glucose transport assays. Pinocembrin exhibited the strongest inhibition of both α-amylase and α-glucosidase, while pinostrobin and the crude extract showed moderate effects. In Caco-2 cells, the crude extract reduced glucose uptake, whereas both flavonoids markedly inhibited transport under glucose-depleted conditions, suggesting interaction with sodium-dependent glucose transporters (SGLTs). Under high-glucose conditions, their effects were minimal, indicating limited activity on facilitative glucose transporters (GLUTs). Moreover, molecular docking studies revealed that pinostrobin and pinocembrin bind within the glucose transporter channels of SGLT1 and SGLT2, blocking glucose passage and supporting the experimental findings. Overall, B. rotunda, particularly pinocembrin, demonstrates notable in vitro antidiabetic potential through enzyme inhibition and SGLT modulation. Further in vivo investigations are warranted to validate its hypoglycemic properties and identify additional active compounds. Full article

The sustainable revalorization of porcine blood is crucial due to the large volumes daily generated in slaughterhouses. The aim of this study was to obtain a novel ingredient rich in free amino acids and bioactive peptides from the sequential hydrolysis of porcine blood. Porcine blood was hydrolyzed with Alcalase 4.0 L and Protana™ Prime enzymes, followed by molecular weight fractionation (<10 kDa) and spray-drying. The antioxidant, hypoglycemic, and anti-inflammatory bioactivities of the resulting hydrolysate (PBSH) were studied in vitro. Further fractionation by reversed-phase high-performance liquid chromatography (RP-HPLC) was performed to isolate the most bioactive fraction based on polarity. Peptides from fraction 1 (F1) were identified using LC-MS/MS and analyzed in silico. Finally, some peptides were synthesized, and their bioactivity was subsequently assessed. PBSH hydrolysate showed antioxidant activity with IC₅₀ values of 2.09, 135.05, and 26.73 mg/mL for ABTS, FRAP, and DPPH assays, respectively. Additionally, PBSH exhibited hypoglycemic, anti-inflammatory, and immunomodulatory potential through the inhibition of DPP-IV (82.78%), NEP (84.72%), TACE (50.79%), and MGL (69.08%) enzymes at a concentration of 20, 20, 100, and 20 mg/mL, respectively. Peptides PDDFNPS, FPPKPKD, DNPIPK, GHLDDLPG, and GDL were identified in the most polar and bioactive fraction (F1) and proved a synergistic hypoglycemic effect at a concentration of 1 mmol/L. The peptide PDDFNPS exhibited multifunctional properties with 56.43% inhibition of DPP-IV and 83.54% inhibition of NEP. PBSH resulted in a novel functional ingredient for animal feed as it contains a variety of identified bioactive peptides and a high amount of free amino acids. Full article

Background/Objectives: Diabetes mellitus (DM) is one of the most common metabolic disorders, with a continually increasing population incidence. One of the main therapeutic approaches for this condition involves the inhibition of alpha-amylase and alpha-glucosidase—key enzymes involved in carbohydrate breakdown. Silver nanoparticles have exhibited inhibitory activity against both enzymes, suggesting their potential in regulating postprandial blood glucose levels. This study aimed to evaluate the antidiabetic potential of silver nanoparticles biosynthesized with Stenocereus queretaroensis flower extract. Methods: The flower extract was prepared and, following a qualitative and quantitative phytochemical analysis, was utilized in the reaction to biosynthesize S. queretaroensis flower extract nanoparticles (SAgNPs). The SAgNPs were characterized using UV–visible spectroscopy, dynamic light scattering (DLS), scanning electron microscopy (SEM), energy dispersive X-ray (EDX), X-ray diffraction (XRD), and Fourier transform infrared spectrophotometry (FTIR). The antidiabetic potential of the biosynthesized SAgNPs was evaluated in vitro using alpha-amylase and alpha-glucosidase inhibitory assays, while an animal model was used for postprandial hypoglycemic activity in healthy mice. Results: The phytochemical analyses showed the presence of phenolic compounds and flavonoids like sinapic acid, p-coumaroyl tyrosine, procyanidin dimer β1, and dihydroquercetin in the flower extract. The SAgNPs were found to be rough and spherical in shape, with an average size of 99.5 nm. The inhibition of alpha-amylase and alpha-glucosidase by SAgNPs exhibited an IC₅₀ of 4.92 µg/mL and 0.68 µg/mL, respectively. The animal model results suggested that SAgNPs at 100 mg/kg caused a significant decrease in the postprandial glucose level; this effect is likely attributable to delayed carbohydrate digestion, as supported by the in vitro findings. Conclusions: S. queretaroensis-synthesized silver nanoparticles may constitute a promising option for antidiabetic therapy. Full article

Noni juice polysaccharides demonstrate promising hypoglycemic activity, but their high molecular weight restricts bioavailability. This study established a controlled degradation approach to optimize the functional properties of Noni juice polysaccharides. Molecular characterization demonstrated that the degraded Noni juice polysaccharides (DNJPs, Mw 191.8 kDa) retained the core monosaccharide composition, while exhibiting enhanced solubility. In vitro experiments with insulin-resistant HepG2 cells showed that DNJPs (0.5–2 mg/mL) significantly enhanced glucose consumption (p < 0.01) and mitigated oxidative stress by upregulating antioxidant enzymes (SOD, CAT, and GSH-Px) and decreasing malondialdehyde (MDA) levels. DNJPs activated the PI3K/AKT-Nrf2-GSK3β signaling axis through a multifaceted mechanism involving the following: upregulating the phosphorylation levels of PI3K and AKT; enhancing Nrf2 nuclear translocation, which in turn promotes the expression of downstream targets such as HO-1 and NQO1; inhibiting GSK3β activity; and suppressing FOXO1-mediated gluconeogenesis. These findings underscore DNJPs as promising functional food ingredients that modulate two key pathways to improve glucose metabolism. Full article