Hypoglycemic Effect Research Articles

Extraction, in vitro hypoglycaemic activity and active ingredient analysis of polyphenols from walnut green husk

A variety of polyphenols in walnut green husk have shown physiological benefits, but their primary hypoglycemic active ingredients remain unclear. We report the extraction of walnut green husk polyphenols (WGHP) and their hypoglycemic effects in vitro. WGHP was extracted using ultrasound-assisted ethanol extraction, with optimization via response surface methodology resulting in 88.0 ± 0.1 % purity after D101 macroporous resin purification. WGHP effectively inhibited α-glucosidase and α-amylase, with IC50 values of 3.42 μg/mL and 2.56 mg/mL, respectively. It also increased glycogen synthesis in insulin-resistant HepG2 cells and enhanced glucose consumption in 3T3-L1 and insulin-resistant HepG2 cells. Screening six α-glucosidase ligands from WGHP using affinity ultrafiltration and UPLC-MS/MS, combined with molecular docking, identified hydrogen bonds and binding energies between the ligands and the enzyme. These results highlight the hypoglycemic potential of walnut green husk polyphenols and provide a basis for future therapeutic research.

Phytochemical Riches, Bioactivities, and Clinical Potential of Prinsepia utilis Royle: A Comprehensive Review

Prinsepia utilis Royle, widely recognized in Chinese and Indian traditional medicine, has attracted significant interest in the realms of phytochemistry and bioactivity research. This deciduous shrub from the Rosaceae family thrives in the Himalayan region at altitudes between 1000 and 3000 meters. The current paper aims to consolidate existing knowledge on P. utilis, providing an updated database of its phytochemical constituents and related bioactivities. Investigations have revealed a wealth of secondary metabolites, including alkaloids, flavonoids, phenolics, and terpenoids. Research has shown that extracts, fractions, and isolated compounds of P. utilis exhibit notable antioxidant, anti‐inflammatory, antimicrobial, enzymatic inhibitory, immunosuppressive, and cytotoxic properties. In vivo studies confirm its traditional uses, demonstrating anti‐inflammatory, anti‐benign prostatic hyperplasia, osteoprotective, and hypoglycemic effects. Effective formulations using P. utilis extract have been developed for atrophic dermatitis and acne vulgaris. These findings underscore the plant's potential as a source of new therapeutic agents and functional additives. Nonetheless, further research is essential to advance pharmacological assessments, clinical trials, and sustainable cultivation methods to fully harness its pharmaceutical and industrial applications.

Correlation analysis between phytochemical composition and biological activities of Artemisiascoparia

As a homologous plant of medicine and food, Artemisia scoparia has rich nutritional value and medicinal components. The main contents are to analyze the phytochemical composition and various biological activities of A. scoparia, and to explore the Pearson correlation between the contents of each phytochemical composition and biological activities. The ethanol extract (EA) and its fractions (n-hexane extract (NHE), ethyl acetate extract (EAC), n-butanol extract (NBA), and water extract (HO)) of A. scoparia were rich in polyphenols, polysaccharides, terpenoids, coumarins, flavonoids and showed potential for antibacterial, antioxidant, hypoglycemic, lipid-lowering, and anti-inflammatory activities. EAC contains the highest amount of coumarins and flavonoids, shows strong antibacterial, antioxidant, hypoglycemic, lipid-lowering and anti-inflammatory (COX-2) activities. In addition, the inhibition rate of NHE on LOX was higher, and Pearson correlation reveled a strong association between phytochemical composition and biological activities: Coumarins had antimicrobial properties, flavonoids had antioxidant and hypoglycemic effects, and flavonoids and terpenoids had anti-inflammatory effects. There was a significant negative correlation between coumarins and MBC of S. aureus (r = 0.84, p < 0.001) and C. albicans (r = 0.84, p < 0.001). Flavonoids (r = 0.86, p < 0.001) showed a significant negative correlation with α-glucosidase scavenging ability. Terpenoids also showed a significantly negative correlation with LOX scavenging ability (r = 0.70, p < 0.001). A comprehensive understanding of both physiological functionalities and potential applications related to the bioactive elements present in extracts from A. scoparia could potentially provide valuable scientific insights to guide its medical or health-related utilization.

Efficacy and safety of cofrogliptin once every 2 weeks in Chinese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled, phase 3 trial.

We conducted a multicentre, randomized phase 3 trial in China to evaluate the efficacy and safety of cofrogliptin (HSK7653), a novel long-acting dipeptidyl peptidase-4 inhibitor, in patients with drug-naïve type 2 diabetes (T2D). Patients with inadequately controlled T2D were randomly assigned (1:1:1) to cofrogliptin 10 mg, cofrogliptin 25 mg or placebo, taken orally once every 2 weeks for a 24-week double-blind period. Eligible patients then received cofrogliptin 25 mg in a 28-week open-label extension. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to week 24. In total, 475 patients (median age: 54.0 years) were randomized and received at least one dose of cofrogliptin 10 mg (n = 158), cofrogliptin 25 mg (n = 158) or placebo (n = 159); 401 patients entered the open-label extension. At week 24, the least-squares (LS) mean difference (95% confidence interval [CI]) in HbA1c versus placebo was -0.63% (-0.81, -0.46) with cofrogliptin 10 mg and -0.59% (-0.77, -0.42) with cofrogliptin 25 mg (both p < 0.0001). The LS mean (standard error) change in HbA1c from baseline was maintained at the end of the study in patients given open-label cofrogliptin 25 mg for an additional 28 weeks: cofrogliptin 10 mg: -0.86% (0.07); cofrogliptin 25 mg: -0.74% (0.07); placebo: -0.89% (0.07). Over the entire study, common adverse events were hyperuricaemia, hyperlipidaemia, hypertriglyceridaemia, increased lipase, upper respiratory tract infection and urinary tract infection. Hypoglycaemic events did not significantly differ between groups. Cofrogliptin provided glycaemic control over 52 weeks and was generally well tolerated in patients with T2D. Registered on Clinicaltrials.gov with the registration number NCT04556851 (https://clinicaltrials.gov/study/NCT04556851).

Loureirin B Ameliorates Glycolipid Metabolism Disorders in Ob/ob Mice by Regulating Bile Acid Levels and Modulating Gut Microbiota Composition.

Loureirin B (LB), an active component of Resina Draconis, exhibits hypoglycemic and hypolipidemic effects; however, its mode of action remains unclear. Here, ob/ob mice were utilized to investigate the effects of LB on the regulation of glucolipid metabolism disorders. Non-targeted metabolomics and 16S rDNA sequencing were performed to elucidate the potential mechanisms involved. Results indicated that LB treatment (45 mg/kg) significantly improved glucose intolerance and insulin resistance, reduced lipid levels, and alleviated hepatic steatosis. Non-targeted metabolomics analysis revealed that LB treatment regulated bile acid levels. Quantification of liver bile acids demonstrated that LB treatment significantly decreased the ratio of 12α-OH to non-12α-OH bile acids in the liver. 16S rDNA sequencing results showed that LB treatment increased the abundance of short-chain fatty acid-producing microbiota while decreasing the abundance of bile salt hydrolase (BSH) enzyme-producing microbiota. In conclusion, LB ameliorates glucolipid metabolism disorders by regulating liver bile acid levels and modulating the composition of the gut microbiota.

Exploring the Potential Antidiabetic Effects of Alkannin (A Naphthoquinone Compound): In Vivo and In Silico Studies

Background It is estimated that the plant has been utilized in India’s traditional medical system for close to 2,500 years. Alkanin is a key active component in Boraginaceae medicinal plant roots. Many scientists are interested in this tiny molecule due to its biological potential. Purpose To examine the hypoglycemic effects of alkannin (a naphthoquinone pigment). Methods Initially, we determined the dosage of alkannin by conducting an acute oral toxicity study per Organisation for Economic Co-operation and Development guidelines. Subsequently, streptozocin was used to induce diabetes in mice, and we chose several parameters such as body weight, food and water intake, blood glucose level, and biochemical estimation for the in vivo evaluation. The enhanced pharmacokinetic features of alkannin, such as its better cytochromes P450 metabolism profiles and higher intestinal absorption as compared to glimepiride, were validated by in silico investigations utilizing Swiss ADME (Absorption, Distribution, Metabolism, and Excretion) and AutoDock Vina. Results In particular, blood glucose levels and body weight in the alkannin-treated group drastically decreased to 138 ± 1.45 mg/dL and 27.9±0.54 g, respectively, as compared with the diabetic-treated group. Moreover, alkaline phosphatase levels dropped to 57.26 ± 3.05 U/L in the alkannin group, suggesting enhanced liver and kidney functions. Creatinine levels also decreased from 1.44 ± 0.10 mg/dL to 0.92 ± 0.09 mg/dL, and serum glutamic oxaloacetic transaminase/aspartate aminotransferase levels decreased from 64.16 ± 3.14 U/L to 47.85 ± 2.01 U/L. Additionally, diabetic controls maintained cholesterol levels between 102.1 ± 11.46 mg/dL and 93.53 ± 2.61 mg/dL. With a considerable binding score of –9.2 kcal/mol for alkannin, molecular docking demonstrated a high degree of binding efficiency and robust interaction with biological targets. The docking results revealed that alkannin exhibits drug-like properties. In addition, it satisfies the lead likeness requirement and has a lower synthetic accessibility score compared to glimepiride. Conclusion The results revealed the promising characteristics and positive outcomes of alkannin, underscoring its potential as a viable candidate for further investigation and prospective advancement as a treatment drug for diabetes.

Development and evaluation of biocompatible coated microneedle array for controlled insulin delivery: Fabrication, characterization, in vitro, and in vivo investigations

Traditional insulin administration for people with diabetes often involves painful injections, leading to discomfort and challenges with patient compliance. A promising alternative to these conventional methods is transdermal insulin delivery using microneedle arrays, which offer a more comfortable way to deliver insulin through the skin. This study introduces an innovative approach using 3D-printed microneedle arrays coated with insulin via a dip-coating process. These microneedles present a compelling alternative to traditional injections, particularly due to their ability to gently pierce the stratum corneum, the outermost layer of skin, while minimizing discomfort. The microneedle arrays were fabricated using biocompatible resin polymers through 3D printing, creating solid conical needles with a length of 1200 µm, a base diameter of 200 µm, a tip diameter of 80 µm, and a needle spacing of 1.2 mm. The insulin coating was achieved by dip-coating the microneedles in a solution of insulin and polyvinyl alcohol (PVA), with careful optimization of the solution concentration, immersion time, and withdrawal speed to ensure a uniform and controlled coating thickness. Mechanical stability and skin penetration capabilities of the microneedles were assessed using skin models such as parafilm and porcine skin. The tests confirmed that the coated microneedles are robust enough to consistently penetrate the skin. In vivo studies with diabetic rats were conducted to evaluate skin irritation, penetration, and drug delivery efficiency. The insulin-coated microneedle arrays successfully penetrated the skin and delivered the drug with approximately 90 % efficiency. The study also showed that the microneedles provided consistent drug delivery, and the skin recovered without any signs of injury. Additionally, the hypoglycemic effect of the insulin-coated microneedles was comparable to that of traditional subcutaneous insulin injections. These findings underscore the potential of microneedle arrays as a painless and effective method for insulin delivery, maintaining stable glucose levels over an extended period. The demonstrated safety and efficacy of the coated microneedles open the door for clinical trials and potential use in diabetic patients, offering a promising advancement in diabetes management.

Eighteen-Month Hybrid Closed-Loop Use in Very Young Children With Type 1 Diabetes: A Single-Arm Multicenter Trial.

We aimed to evaluate the longer-term safety and efficacy of hybrid closed-loop (CL) therapy in very young children with type 1 diabetes (T1D). Following a 16-week multinational, randomized crossover trial comparing hybrid CL with sensor-augmented pump (SAP) therapy in 74 very young children aged 1-7 years with T1D, participants were invited to an extension phase using CL for a further 18 months. Outcomes were compared with the primary-phase SAP period and primary-phase CL period. After the primary study phase, 60 participants were eligible to enroll in the extension. Of these, 49 consented (mean ± SD age 6.6 ± 1.5 years) to continue use of CL for 18 months. Percentage time in range (TIR) 3.9-10.0 mmol/L was 8.4 percentage points (95% CI 6.7 to 10.1; P < 0.001) higher, while HbA1c was 0.4% ([5.0 mmol/mol], 95% CI 0.3 to 0.6 [3.7 to 6.2]; P < 0.001) lower during the CL extension phase compared with primary-phase SAP period. At 18 months, mean HbA1c was 6.7 ± 0.5% and TIR was 70 ± 7%, compared with 6.7 ± 0.5% and 71 ± 6% in the primary-phase CL period. Time in hypoglycemia (<3.9 mmol/L) was similar between CL extension phase and both primary-phase SAP (P = 0.31) and CL periods (P = 0.70). There were two severe hypoglycemia events and one other serious adverse event during the extension phase. One unexpected serious adverse device effect occurred. Use of the Cambridge hybrid CL system led to sustained improvements in glycemic control lasting more than 18 months in very young children with T1D.

Proposed mechanisms of action participating in the hypoglycemic effect of the traditionally used Croton guatemalensis Lotsy and junceic acid, its main compound.

Croton guatemalensis Lotsy (Euphorbiaceae) is an important traditional medicine that is used by the Cakchiquels of Guatemala to control hyperglycemia in patients with type 2 diabetes. Previous studies have shown that administration of this plant induces an acute hypoglycemic effect during fasting and that the main compound is junceic acid, a diterpenoid with a clerodane skeleton; however, junceic acid has not been reported to have hypoglycemic activity in the literature. As the mechanisms involved in the hypoglycemic effect of C. guatemalensis remain unknown, the objective of the present investigation was to elucidate the hypoglycemic mechanisms of this species, as well as its major compound, junceic acid. The results indicated that, similar to complete extract, junceic acid exhibited a hypoglycemic effect in hyperglycemic rats. Both C. guatemalensis extract and junceic acid inhibited the activity of two rate-limiting enzymes involved in hepatic glucose production; however, compared with chlorogenic acid, junceic acid had a more potent effect on glucose-6-phosphatase levels than chlorogenic acid, which was used as a positive control. Furthermore, both fasting and postprandial insulin levels decreased in healthy and hyperglycemic rats despite reduced blood glucose levels in both metabolic states, suggesting a potential insulin-sensitizing effect. However, neither of these compounds potentiated the effect of insulin in insulin tolerance tests nor inhibited the enzyme activity of protein tyrosine phosphatase 1B, a negative regulator of the insulin pathway. Therefore, the insulin-sensitizing effect is thought to be independent of insulin and mediated by potential activation of the AMP-activated protein kinase pathway. The specific activation of this master regulator in β-cells results in the inhibition of insulin secretion in a healthy state and the restoration of the insulin response under conditions of glucotoxicity; these effects were observed after the administration of the extract and junceic acid in healthy and hyperglycemic rats. Overall, the main findings of this study establish a basis of the mechanisms of action of C. guatemalensis and its main compound, junceic acid, in terms of their hypoglycemic effect.

Don´t give up on mitochondria as a target for the treatment of diabetes and its complications

In this editorial, we discuss an article by Wang et al , focusing on the role of mitochondria in peripheral insulin resistance and insulin secretion. Despite numerous in vitro and pre-clinical studies supporting the involvement of mitochondrial dysfunction and oxidative stress in the pathogenesis of diabetes and its complications, efforts to target mitochondria for glycemic control in diabetes using mitochondria-targeted antioxidants have produced inconsistent results. The intricate functionality of mitochondria is summarized to underscore the challenges it poses as a therapeutic target. While mitochondria-targeted antioxidants have demonstrated improvement in mitochondrial function and oxidative stress in pre-clinical diabetes models, the results regarding glycemic control have been mixed, and no studies have evaluated their hypoglycemic effects in diabetic patients. Nonetheless, pre-clinical trials have shown promising outcomes in ameliorating diabetes-related complications. Here, we review some reasons why mitochondria-targeted antioxidants may not function effectively in the context of mitochondrial dysfunction. We also highlight several alternative approaches under development that may enhance the targeting of mitochondria for diabetes treatment.

The Emerging Role of GLP-1 Agonists in Burn Care: What Do We Know?

Glucagon-like peptide-1 (GLP-1) agonists mimic the action of GLP-1, a hormone that regulates blood glucose levels via stimulation of insulin release and inhibition of glucagon secretion. After burn, the current literature suggests that the use of GLP-1 agonists results in less insulin dependence with similar glucose control and hypoglycemic events to patients receiving a basal-bolus insulin regimen. GLP-1 agonists may also promote wound healing through various mechanisms including angiogenesis and improved keratinocyte migration. Despite the potential benefits, GLP-1 agonists reduce gastrointestinal motility which impacts their widespread adoption in burn care. This dysmotility can result in inadequate nutrition delivery, unintentional weight loss, and is a potential aspiration risk. The net impact of these medications on burn patients is unclear. Given their potential to demonstrate the safety, efficacy, and optimal dosing of various GLP-1 agonists in acute burn management.

Research Progress on the Quality, Extraction Technology, Food Application, and Physiological Function of Rice Bran Oil.

Rice bran oil is recommended by the World Health Organization as one of the three major healthy edible oils (along with corn and sesame oils), owing to its unique fatty acid composition and functional components. This study screened, organized, and analyzed a large number of studies retrieved through keyword searches, and investigated the nutritional value and safety of rice bran oil. It reviews the stability of raw rice bran materials and the extraction and refining process of rice bran oil and discusses food applications and sub-health regulations. Research has found that a delayed stabilization treatment of rice bran seriously affects the overall quality of rice bran oil. Compared with traditional solvent extraction, the new extraction technologies have improved the yield and nutritional value of rice bran oil, but most of them are still in the research stage. Owing to the lack of economical and applicable supporting production equipment, extraction is difficult to industrialize, which is a challenging research area for the future. Rice bran oil has stronger antioxidant stability than other edible oils and is more beneficial to human health; however, its application scope and consumption are limited owing to the product price and lack of understanding. Rice bran oil has significant antioxidant, anti-inflammatory, anti-cancer, hypoglycemic, lipid-lowering, and neuroprotective effects. Further exploratory research on other unknown functions is required to lay a scientific basis for the application and development of rice bran oil.

Research progress and application of pectin: A review.

Pectin, an acidic polysaccharide, is naturally present primarily in the cell walls and inner layers of higher plants. Pectin is extensively used in food, pharmaceutical, cosmetic, and other industries owing to its exceptional attributes encompassing superior gelation, emulsification, antioxidant activity, stability, biocompatibility, and nontoxicity. Due to the increasing demand for pectin, there is a short supply in the domestic pectin market. Currently, the domestic production of pectin is heavily reliant on imports, thus emphasizing the urgent need to enhance its local manufacturing capabilities. Due to the diverse sources of pectin and variations in extraction and purification methods, its content, physicochemical properties, and biological activity are influenced, consequently impacting the market application of pectin. Therefore, this paper comprehensively reviews the extraction and purification process of pectin, in vivo metabolism, and biological activities (including antitumor, immunomodulatory, anti-inflammatory, antioxidant, hypoglycemic and hypolipidemic effects, antimicrobial properties, accelerated wound healing potential, promotion of gastrointestinal peristalsis, and alleviation of constipation as well as cholesterol-lowering effect). Furthermore, it explores the diverse applications of pectin in food science, biomedicine, and other interdisciplinary fields. This review serves as a valuable resource for enhancing the efficiency of pectin content improvement and exploring the potential value and application of pectin in a more scholarly and scientifically rigorous manner.

Cardiomodulatory Effects of Cardiometabolic and Antihyperglycemic Medications: The Roles of Oxidative and Endoplasmic Reticulum Stress.

Uncontrolled hyperglycemia in people with diabetes is an established risk of premature cardiovascular disease. Repeated hypoglycemic events are also associated with increased cardiovascular mortality. Both hyperglycemia and hypoglycemia induce cellular stress, notably endoplasmic reticulum (ER) stress, a known promoter of cardiovascular disease. Contemporary anti-hyperglycemic drugs such as glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors simultaneously inhibit oxidative stress and ER stress in human coronary artery endothelial cells. Similarly, other known cardioprotective drugs, such as statins and inhibitors of the renin-angiotensin-aldosterone system (RAAS) share a common pleiotropic effect of reducing cellular stress. Antioxidants reduce oxidative stress but may aggravate ER stress. This dichotomy of antioxidant effects may underline the unfavorable outcomes of clinical trials with antioxidant vitamin use. The aim of this review is to highlight the potential role of cellular stress reduction in cardioprotective effects of contemporary diabetes drugs. Future clinical trials are needed to test the hypothesis that cellular stress is the fundamental culprit in cardiovascular disease.

Effect of glucagon-like peptide-1 receptor agonists on prostate cancer: A review.

Glucagon-like peptide-1 receptor agonist (GLP-1RA) is widely used in the treatment of type 2 diabetes mellitus (T2DM) for its significant hypoglycemic effect, weight loss and small side effects. Some studies have shown that GLP-1RA has an inhibitory effect on prostate cancer, and its application will produce adverse effects associated with an increased or decreased risk of some tumors. GLP-1R is widely expressed by various types of cells and tissues in the human body, so GLP-1RA has attracted wide clinical attention to the occurrence, development and prognosis of tumors, which brings more new directions and hopes for the treatment of prostate cancer. This paper describes the expression of glucagon-like peptide-1 receptor (GLP-1R) in prostate cancer and the effects of glucagon-like peptide-1 receptor agonist (GLP-1RA) on prostate cancer.

Hypoglycemic effects of white hyacinth bean polysaccharide on type 2 diabetes mellitus rats involvement with entero-insular axis and GLP-1 via metabolomics study

The present study aimed to investigate the potential effects of white hyacinth bean polysaccharide (WHBP) against type 2 diabetic mellitus (T2DM) which was established by high-glucose/high-fat for 8 weeks, combined with a low-dose streptozotocin (STZ) injection. Our results showed that WHBP behaved the hypoglycemic effect by attenuating fasting blood glucose in vivo. WHBP-mediated anti-diabetic effects associated with the attenuation of insulin resistance and pancreatic impairment, as evidenced by the mitigation of pathological changes, inflammatory response and oxidative stress in the pancreas of T2DM rats. Meanwhile, gut protection was also shown during WHBP-mediated anti-diabetic effects, and glucagon-like peptide-1 (GLP-1), a mediator of the entero-insular axis, was observed to be elevated in both gut and pancreas of WHBP groups when compared to DM group, suggesting that hypoglycemic effects of WHBP were implicated in gut-pancreas interaction. Subsequently, untargeted metabolomics analysis performed by UPLC-QTOF/MS and showed that WHBP administration significantly adjusted the levels of 40 metabolites when compared to DM group. Further data concerning pathway analysis showed that WHBP administration significantly regulated the phenylalanine metabolism, tryptophan metabolism, arginine and proline, isoleucine metabolism, and glycerophospholipid metabolism in T2DM rats. Together, our results suggested that WHBP performed hypoglycemic effects and pancreatic protection linked to entero-insular axis involvement with GLP-1 and reversed metabolic disturbances in T2DM rats.

Hypoglycemic Effect of Rambutan (Nephelium lappaceum L.) Peel Polyphenols on Type 2 Diabetes Mice by Modulating Gut Microbiota and Metabolites.

Type 2 diabetes mellitus (T2DM) is a metabolic disease with a major global public health effect. Rambutan peel polyphenols (RPPs) have been reported to exert hypoglycemic activity. However, few studies have been explored from the viewpoint of gut microbiota and its metabolites. RPPs are administered by gavage to a mice model of T2DM established by using a high-fat diet combined with streptozotocin. It finds that RPPs treatment alleviates hyperglycemia symptoms by improving glucolipid metabolism and liver function. Immunohistochemistry indicates that the antihyperglycemic effect of RPPs is regulated by the IRS-1/PI3K/AKT/GSK3β signaling pathway. RPPs treatment remodels the structure of gut microbiota (Odoribacter, Lachnospiraceae_NK4A136_group, Lactobacillus, Turicibacter, Erysipelatoclostridium, and Tuzzerella) and enriches the metabolites (RPPs-derived urolithins, short-chain fatty acids, dehydrocholic acid, (+)-catechin, dihydroberberine, pterostilbene, and artesunate) associated with diabetes regulation in T2DM mice. The effects of RPPs in ameliorating glycolipid metabolism disorders are correlated with differential gut microbiota and metabolites. The gut microbiota and its metabolites are key targets for the hypoglycemic effects of RPPs.

Quercetin: Potential antidiabetic effects through enzyme inhibition and starch digestibility

AbstractDiabetes mellitus involves high blood sugar levels due to insufficient insulin action. Furthermore, enzymes such as α‐amylase and α‐glucosidase break down carbohydrates into glucose, leading to postprandial hyperglycemia. Flavonoids, particularly quercetin, inhibit these enzymes, slowing carbohydrate digestion and reducing glucose absorption. Quercetin has significant hypoglycemic effects with inhibitory concentration (IC50) values comparable to acarbose, a standard inhibitor, suggesting its potential as a natural alternative for diabetes management. In silico models, including molecular docking, molecular dynamics (MD) simulations, and quantitative structure‐activity relationship (QSAR) approaches, help researchers understand the molecular interactions of therapeutic agents. These techniques identify potential inhibitors, determine enzyme‐inhibitor structures, and calculate binding energies, correlating findings with in vitro or in vivo data. Molecular docking predicts molecular orientations, MD simulations offer insights into enzyme–inhibitor dynamics, and QSAR models predict inhibitory potential based on structural properties. Studies have shown that quercetin effectively inhibits α‐glucosidase and α‐amylase by forming hydrogen bonds with specific amino acid residues. Quercetin interacts with starches and reduces their digestibility, increases the formation of resistant starch, lowers the glycemic index, and inhibits digestive enzymes. Studies show that the effects of quercetin on starch digestion vary with concentration and type of starch, and its incorporation into foods such as bakery products, pasta, etc. can significantly decrease starch hydrolysis. The incorporation of quercetin into starch matrices may aid in the development of functional foods aimed at improving glycemic control.

Selenium polysaccharide form sweet corn cob mediated hypoglycemic effects in vitro and untargeted metabolomics study on type 2 diabetes

Type 2 diabetes mellitus (T2D) causes complications due to metabolic disorders besides increasing blood glucose. Sweet corn cob selenium polysaccharide (SeSCP) is a complex of Se with Sweet corn cob polysaccharide that has good hypoglycemic efficacy, but its effect on T2D metabolism has not been determined. In this study, the hypoglycemic effect of SeSCP was investigated by in vitro and in vivo experiments, and the levels of metabolites in feces were analyzed in a high-fat diet and STZ-induced T2D mouse model by Liquid chromatography-mass spectrometry (LC-MS). The results indicated that SeSCP regulates α-amylase and α-glucosidase through competitive reversible inhibition, and the reaction is spontaneous, driven by van der Waals forces and hydrogen bonding. In vivo, SeSCP modulates glucose transport decreasing glucose entry into the bloodstream. The metabolites mainly affected by SeSCP-MC were adenine, LysoPA (0:0/18:2(9Z, 12Z)), cysteine-S-sulfate, and demeclocycline (hydrochloride) metabolites. SeSCP interfered with β-alanine metabolism, starch and sucrose metabolism, ether lipid metabolism, glycerophospholipid metabolism, glyoxylate and dicarboxylate metabolism, pantothenate and CoA biosynthesis, etc. Additionally, SeSCP exhibited more effective metabolic interventions than metformin and SCP. Therefore, SeSCP can reduce complications while improving T2D blood glucose.

A Neutral Polysaccharide from Medicago Sativa L.: Structural Properties and Hypoglycemic Activity In Vitro and In Vivo.

Medicago sativa polysaccharides (MSPs) are beneficial compounds extracted from Medicago sativa L. that exhibit multiple medicinal activities. However, little is known about their hypoglycemic effects. In this study, MSP-II-a, a neutral polysaccharide with an Mw of 4.3×104 Da, was isolated and purified from M. sativa L. Monosaccharide composition analysis determined that MSP-II-a was composed of arabinose, glucose, galactose, mannose, rhamnose, and xylose in a molar ratio of 2.1 : 4.0 : 1.1:0.4 : 1.4 : 1.1. Structural characterization of MSP-II was performed using a combination of methylation analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. The results showed that MSP-II-a was mainly comprised of 1,4-p-Glc, 1,3,4-Rha, and 1,3-p-Gal glycosidic linkages, revealing a mesh-like texture with irregular blade shapes. In vitro assays demonstrated that MSP-II-a, at concentrations of 200 and 400 μg/mL, promoted glucose uptake in insulin-resistant 3T3-L1 adipocytes. In vivo studies have shown that MSP-II-a significantly alleviates insulin resistance by reducing fasting blood glucose levels and increasing hepatic glycogen synthesis in HFD/STZ-induced diabetic mice. These findings revealed that MSP-II-a is a promising source of bioactive polysaccharides with potential hypoglycemic activity.