Search Results (381)

This review aims to compare the biological properties of eleven fruits of the Prunus species, with the focus on their potential in the prevention and management of chronic diseases. The search spanned publications from 2000 to May 2026, only in English, and utilized databases such as PubMed, Web of Science, and Google Scholar, focusing on the in vitro and in vivo studies. The exclusion criteria included review articles, studies focusing exclusively on isolated phytochemicals or synthetic derivatives from Prunus species, and in silico or theoretical analyses. The fruits of Prunus species exhibited a broad spectrum of activities, including antioxidant, anti-inflammatory, anticancer, antihyperglycemic, or neuroprotective. Interestingly, sour cherries exhibited sleep-enhancing, and xanthine oxidase-inhibitory effects, while apricots showed promising hepatoprotective activity. Key species, including apricots, cherries, peaches, and plums, are widely recognized for their bioactive phytochemicals and potential health benefits, while some (e.g., bird cherry, blackthorn) are less examined, although promising. Prunus fruits revealed health-benefit potential, that at least partially supports their ethnopharmacological uses. However, further clinical and mechanistic studies are warranted to validate their efficacy and explore potential applications in pharmaceutical formulations. Full article

This study aimed to determine the absolute bioavailability of quercetin and quantitatively evaluate its pharmacokinetic–pharmacodynamic (PK-PD) relationship regarding acute glucose-lowering effects in normoglycemic and alloxan-induced diabetic rats, addressing whether its in vivo efficacy is driven by the free aglycone or its biotransformed intermediates. Healthy and diabetic rats received single doses of quercetin either orally (75 mg/kg) or intravenously (38 mg/kg). Plasma concentrations of free quercetin were quantified using a validated HPLC-DAD method, and temporal PK-PD relationships between systemic exposure and the percentage variation of glycemia were mathematically evaluated employing Pearson correlation analysis. The absolute bioavailability of free quercetin was significantly impaired by the pathophysiological state, dropping from 59.7% in healthy rats to 40.9% in diabetic subjects. Despite this diminished systemic exposure, oral administration elicited significant hypoglycemic responses. Crucially, the Pearson correlation analysis revealed a pronounced temporal dissociation: the onset of glycemic reduction occurred independently of the maximal circulating concentration of free quercetin. Furthermore, intravenous delivery bypassed first-pass barriers and induced a markedly faster and deeper hypoglycemic effect (up to −47% in diabetic rats). Finally, the diminished bioavailability under diabetic conditions and the stark PK-PD temporal dissociation strongly suggest that quercetin’s acute antihyperglycemic effect is driven by rapid hepatic Phase II biotransformation, implicating conjugated metabolites (rather than the free aglycone) as the principal pharmacological effectors. Full article

Background/Objectives: Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia, dyslipidemia, and oxidative stress, leading to severe systemic complications. Medicinal plants rich in polyphenolic compounds have gained increasing attention as complementary therapeutic agents. This study aimed to comparatively evaluate the chemical composition, as well as the antidiabetic, hypolipidemic, and antioxidant effects of Polygonum persicaria and Vaccinium myrtillus in a streptozotocin-induced diabetic model. Although Vaccinium myrtillus has been more extensively investigated for its antidiabetic potential, the pharmacological relevance of Polygonum persicaria in diabetes remains insufficiently characterized, particularly in direct comparison with a recognized phytotherapeutic comparator. Methods: Hydroalcoholic tinctures prepared from Polygonum persicaria L. herb and Vaccinium myrtillus L. leaves were subjected to phytochemical analysis using High-Performance Thin-Layer Chromatography (HPTLC) for the identification of flavonoids and phenolcarboxylic acids, alongside spectrophotometric determination of total polyphenol and flavonoid content. Experimental diabetes was induced in CD1 mice by streptozotocin administration. Animals were treated orally for 35 days, and glycemic parameters, lipid profile, body weight, food and water intake, and oxidative stress markers (MDA, SOD, TAC, and GPx) were evaluated. Results: HPTLC/CSS screening indicated the presence of rutin, chlorogenic acid, and caffeic acid in Polygonum persicaria, while Vaccinium myrtillus showed stronger densitometric signals for phenolcarboxylic acid-type compounds, particularly chlorogenic and caffeic acids. Total polyphenol and flavonoid content were also higher in Vaccinium myrtillus (433.89 ± 8.67 mg/L GAE; 154.38 ± 3.08 mg/L QE) compared to Polygonum persicaria (269.28 ± 5.25 mg/L GAE; 132.75 ± 2.65 mg/L QE). Functionally, Vaccinium myrtillus demonstrated a significant antihyperglycemic effect from day 14 (p = 0.009) and improved lipid parameters, while Polygonum persicaria showed a delayed glycemic effect, significant only at day 35 (p = 0.014), without significant hypolipidemic activity. In contrast, Polygonum persicaria exerted a marked antioxidant effect, significantly increasing GPx activity (p = 0.025) and reducing MDA levels (p = 0.053). Conclusions: Vaccinium myrtillus showed stronger antihyperglycemic and hypolipidemic effects, while Polygonum persicaria was mainly associated with antioxidant-related biochemical changes. These differences may be influenced by phytochemical composition, but they cannot be attributed solely to total polyphenol or flavonoid content. Full article

Diabetes mellitus is a complex metabolic disorder whose management has moved from glycemic control to the control of risk factors through the use of new antihyperglycemic drugs with pleiotropic effects. Despite the multiple cardio–renal benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors, their prescription is often avoided due to concerns regarding side effects. This review aims to discuss the multiple benefits of SGLT2 inhibitors in balance with one of the most concerning side effects, the risk of euglycemic diabetic ketoacidosis (EDKA). A literature search was performed to identify and select articles relevant to this topic. We accessed several databases, including PubMed, Web of Science and Scopus, using appropriate keywords. We selected and evaluated randomized controlled trials, retrospective studies, systematic reviews and meta-analysis published between 2014 and 2024 supporting the multifaceted benefits of SGLT2 inhibitors and the limitations of their recommendations and focusing on the risk of EDKA. Initially designed as antidiabetic agents, SGLT2 inhibitors have demonstrated important cardio–renal benefits, these drugs being the first-line medication in patients with established cardiovascular disease, heart failure and chronic kidney disease. SGLT2 inhibitors are associated with some potential side effects, but with contradictory data concerning their prevalence and clinical relevance. From the possible side effects, EDKA is a life-threatening metabolic emergency whose incidence and recognition has increased, in particular with the use of SGLT2 inhibitors. These drugs can cause this disorder through several mechanisms, including reduced insulin secretion and increased glucagon levels, leading to free fatty acid production, which generally occurs in the presence of some risk factors such as reduced dietary carbohydrates, intercurrent illnesses, surgical stress and alcohol consumption. Through awareness of these risk factors as well as of the clinical symptoms, this condition could be promptly avoided or managed and SGLT2 inhibitors could be safely used. Full article

Tamarindus indica L. (tamarind) is a traditionally consumed food and medicinal plant with increasing relevance in the development of functional foods and bioactive natural ingredients. While the fruit pulp has been extensively utilized in food products, other fractions, including seeds, shells, and leaves, remain comparatively underexploited despite emerging evidence of notable nutritional and phytochemical value. This review summarizes recent progress regarding the nutritional composition, phytochemical characteristics, biological activities, safety considerations, and industrial applications of different parts of tamarind. These studies indicate that tamarind is rich in carbohydrates, dietary fiber, proteins, minerals, vitamins, polysaccharides, and phenolic compounds, which are associated with anti-oxidant, antihyperglycemic, hypolipidemic, anti-microbial, anti-inflammatory, and prebiotic effects. Nevertheless, most evidence is derived from in vitro and animal studies, while human clinical data remain scarce. In addition to their biological activities, tamarind-derived materials have shown promise in food formulation, pharmaceutical excipients, packaging systems, and environmental applications. Although these advances have been achieved, several challenges remain in compositional standardization, extraction efficiency, safety assessment, and clinical validation. Therefore, future research should focus on establishing standardized methods, optimizing extraction processes, improving safety evaluation systems, and conducting rigorous clinical trials to support the sustainable utilization of tamarind resources. Overall, this review provides a comprehensive scientific basis for the value-added development and sustainable utilization of tamarind resources. Full article

Diabetes mellitus, particularly type 2 diabetes mellitus, is a growing global health burden characterized by chronic hyperglycemia and insulin resistance. Alpha-mangostin (AM), a xanthone from Garcinia mangostana pericarp, exhibits antioxidant, anti-inflammatory, and metabolic regulatory properties in preclinical models. We performed a systematic review and meta-analysis of controlled in vivo studies to assess AM’s anti-hyperglycemic effects. Fourteen studies (25 comparisons) in rodent models of diabetes or hyperglycemia were included. Primary outcome was blood glucose; secondary outcomes were glycated hemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). Random-effects meta-analysis demonstrated that AM significantly reduced fasting blood glucose (mean difference (MD) = −8.75 mmol/L; 95% CI: −10.73 to −6.78; p < 0.001) and HbA1c (MD = −2.20%; 95% CI: −3.07 to −1.32; p < 0.001). AM did not significantly alter circulating insulin (Hedges’ g = 0.43; 95% CI: −0.62 to 1.49; p = 0.42) but improved insulin resistance as measured by HOMA-IR (MD = −0.90; 95% CI: −1.68 to −0.12; p = 0.02). Subgroup, sensitivity, and risk-of-bias analyses supported the robustness of the glucose-lowering association, although substantial between-study heterogeneity was present. Overall, this study provides preclinical evidence that AM exerts significant antihyperglycemic and insulin-sensitizing effects, supporting its potential as a multitarget metabolic modulator. Further standardized and mechanistically informed studies are warranted to facilitate translational progression. Full article

Background/Objectives: Exploiting the metabolic properties of postbiotics is a novel strategy for managing metabolic disorders, including diabetes. Inactivated microorganisms, a major class of postbiotics, improve glycemic control in preclinical and clinical studies. Here, we examined whether heat-killed (HK) Mycobacterium aurum (M. aurum) exerts prophylactic or therapeutic anti-hyperglycemic effects in diabetic mice. Methods: Diabetes was induced in male BALB/c mice by streptozotocin (STZ; 150 mg/kg) injection. HK M. aurum (1 mg) was given orally (three prophylactic doses before STZ) or intradermally (six weekly therapeutic doses after STZ). We assessed glycemic parameters, serum C-peptide/insulin (ELISA), and tissue protein expression (Western blot). Results: Neither route altered body weight or glucose homeostasis in non-diabetic mice. In STZ-diabetic mice, oral prophylactic treatment significantly attenuated hyperglycemia (39–60% reduction weeks 5–8 post-STZ) and showed a trend toward improved serum C-peptide, but did not affect dysregulated expression of skeletal muscle (SM), hepatic, pancreatic and renal proteins involved in glucose transport (GLUT2, GLUT4, and SGLT2), glycolysis (α-LDH), mitochondrial uncoupling (UCP2 and UCP3), and antioxidant defense (CAT). Therapeutic intradermal administration significantly decreased blood glucose (~30% at week 5, ~40% at week 6) and modestly enhanced insulin secretion. Hepatic UCP2 and α-LDH and SM UCP3 protein levels were normalized toward non-diabetic levels, whereas hepatic GLUT2 and SM GLUT4 remained largely unchanged. These correlative findings suggest effects independent of insulin-dependent glucose transport, but do not demonstrate direct functional improvement in mitochondrial or redox status. Conclusions: HK M. aurum exerts partial anti-hyperglycemic effects in STZ-induced diabetic mice, but the associated protein changes require functional validation before its role as a postbiotic in β-cell dysfunction can be established. Full article

In this paper, we review the literature regarding metformin’s action on blood lipid concentrations in metformin-treated diabetic patients. Published data indicate that metformin reduces serum total cholesterol (T-C), LDL-cholesterol (LDL-C) and triacylglycerol (TAG) concentrations and raises serum HDL-cholesterol (HDL-C) concentrations in diabetic patients. The beneficial effect of metformin on serum lipid profiles in diabetic patients can result from (a) its action on AMP-activated protein kinase, which inhibits lipogenesis and cholesterol synthesis and stimulates fatty acid oxidation; (b) decreased plasma TAG concentrations, via promoting VLDL-TAG clearance by brown adipose tissue; (c) the inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression, affecting lipid profile in diabetic patients; (d) the inhibition of the expression of genes encoding proprotein convertase subtilisin/kexin 9 (PCSK9) and lipogenic enzymes; (e) the downregulation of carbohydrate-response element-binding protein (ChREBP), which affects liver TAG and cholesterol synthesis from acetate formed by gut microbiota; (f) the inhibition of angiopoietin-like 3 protein (ANGPTL3) gene expression, and consequent effects on plasma TAG concentrations; (g) the activation of AMPK, which inhibits LXRα activity; and (h) reverse cholesterol transport. In conclusion, one can assume that beyond its primary antihyperglycemic effect, metformin exerts pleiotropic effects that modulate lipid metabolism and blood lipid profile in T2D patients. These beneficial effects of metformin on blood lipid profile may play a role in the reduction in cardiovascular risk in diabetic patients. Full article

Peucephyllum schottii is an aromatic desert plant of the family Asteraceae, which has little scientific research regarding its phytochemical composition and pharmacological properties. This study aims to evaluate in detail the chemical composition and antioxidant, antibacterial, antidiabetic, and cytotoxic activities of the ethanol extract of P. schottii leaves. The chemical composition of the plant extract was analyzed by GC-MS. Total phenolic (TPC) and flavonoid (TFC) contents of the plant were calculated. An antioxidant assay of the plant material was performed by using the DPPH and ABTS tests. The antibacterial activities of P. schottii plant material against six pathogenic bacteria were studied by using the agar diffusion and MIC/MBC techniques. Colorimetric analysis, for its part, enabled the assessment of its antihyperglycemic activities (α-amylase and α-glucosidase) and its cytotoxic activities (in MCF-7 and HepG2 cells). The expressions of apoptotic proteins (caspases, Bcl2, and Bax), were analyzed by RT-PCR. The GC-MS findings showed the presence of complex phytoconstituents of P. schottii in the form of linoleic acid (19.48%), hexadecanoic acid (15.01%), and vitamin E (12.15%). There is high TPC (118.18 mg of GAE/g) and TFC (75.56 mg of QE/g) in P. schottii plant material. The plant showed significant antioxidant (≈105 μg/mL IC₅₀ in DPPH and ≈80 μg/mL IC₅₀ in ABTS) and broad-spectrum antibacterial activities, mostly against E. coli (MIC = 4.68 μg/mL), as well as antihyperglycemic activities against α-amylase (IC₅₀ = 334 μg/mL) and α-glucosidase (IC₅₀ = 196 μg/mL) enzymes. The plant material showed cytotoxic effects in MCF-7 and HepG2 cells in a concentration-dependent manner (IC₅₀ = 78 ± 1.13 μg/mL and 68.23 ± 2.41 μg/mL, respectively). These findings point to P. schottii leaf extract’s potential as a natural antioxidant, antibacterial, antidiabetic, and chemopreventive agent. Full article

Hemoglobin A1c is a central biomarker for long-term glycemic control and a key predictor of diabetes-related complications. The COVID-19 pandemic disrupted routine healthcare delivery and introduced potential metabolic effects of SARS-CoV-2 infection, yet the long-term impact of COVID-19 on glycemic trajectories in individuals with diabetes remains unclear. In this retrospective study, we leveraged harmonized electronic health record data from the National Clinical Cohort Collaborative to evaluate changes in HbA1c before and after documented SARS-CoV-2 infection in adults with diabetes (n = 93,320). Patients were required to have repeated HbA1c measurements pre- and post-infection and stable exposure to key antihyperglycemic medications. A paired statistical analysis was used to identify individuals with statistically significant post-infection changes in HbA1c. We then developed and evaluated multiple supervised machine learning classifiers using an 80/20 train–test split and cross-validation to assess demographic, clinical, and structural factors associated with significant glycemic change. Most patients (71%) did not experience a statistically significant change in average HbA1c following COVID-19 infection, and among those who did, decreases were more common than increases. A random forest classifier achieved the best overall performance, and feature importance and SHAP analyses highlighted body mass index, insulin use, age, and socioeconomic proxies as key contributors. These findings suggest that while COVID-19 infection does not substantially alter long-term glycemic control for most patients with diabetes, individual-level clinical and structural factors influence post-infection glycemic variability. Full article

Annona cherimola is a plant species widely used in Mexican traditional medicine, particularly in the management of diabetes. This study aimed to investigate the antihyperglycemic properties of the petroleum ether extract of A. cherimola leaves (PEEAcL), as well as to evaluate their effects on glycated hemoglobin and toxicity. In addition, the work was directed to determine its potential as an SGLT-1 and α-glucosidase inhibitor. The effect as a potential SGLT-1 and α-glucosidase inhibitor of PEEAcL was evaluated utilizing intestinal glucose absorption (IGA), oral glucose tolerance (OGT), oral sucrose tolerance (OST) and intestinal sucrose hydrolysis (ISH) tests. PEEAcL administered at doses of 200 mg/kg showed significant antihyperglycemic activity after 1 h of treatment, and the maximum effect was seen at 4 h in male and female diabetic mice. In the OST, OLT, and OGT tests, PEEAcL generated a reduction in the postprandial glucose peak at 2 h after the administration of a carbohydrate load, showing an effect comparable to that of acarbose and canagliflozin. In the IGA trial, PEEAcL significantly reduced glucose uptake in the small intestine. Similarly, in the ISH, PEEAcL recorded a significant reduction in glucose concentration in the external aqueous medium. Taken together, these results suggest that the antihyperglycemic effect of PEEAcL could be mediated, at least in part, by inhibition of SGLT-1 and the enzyme α-glucosidase. Full article

Roselle beverage residue (RBR), a by-product of Hibiscus sabdariffa L. processing, retains bioactive compounds, including soluble and insoluble dietary fiber and polyphenols. Its antihyperglycemic effect in type 2 diabetes mellitus (T2DM) has been previously demonstrated; however, its role in lipid metabolism remains unknown. This study assessed the preventive and therapeutic potential of RBR on dyslipidemia and hepatic steatosis in a rodent model of late-stage T2DM characterized by hyperglycemia and hypoinsulinemia. Male Wistar rats with T2DM induced by a high-fat and high-fructose diet combined with streptozotocin received 6% RBR supplementation as either a preventive intervention (starting at week 1 in healthy rats or week 9 in insulin-resistant rats) or a therapeutic intervention (starting at week 14 in diabetic rats). After 17 weeks, RBR supplementation significantly reduced serum triglycerides and total cholesterol, attenuating hepatic lipid accumulation regardless of the timing of intervention. Hepatic Acadm expression, involved in fatty acid β-oxidation, was significantly upregulated in rats treated with RBR from week 1 and 9, whereas no significant modulation was observed for genes related to fatty acid synthesis or uptake. These findings suggest that RBR supplementation may contribute to improving lipid metabolism and hepatic steatosis in a rat model of late-stage T2DM. Full article

Ixora chinensis Lam. has traditionally been used to treat conditions such as acne, high blood pressure, bleeding, tuberculosis, and rheumatism. This study aimed to investigate the methanolic extract of I. chinensis leaves to determine their bioactive compounds and evaluate their effects on both central and peripheral pain using in vivo and in silico approaches. The GC-MS analysis revealed 41 phytochemicals, including 14 phenolics, 4 esters, 12 terpenoids, 8 alkaloids, and 3 sulfur-containing compounds. In the glucose tolerance test, both the chloroform-soluble fraction (CF) and n-hexane fraction (NHF) exhibited p < 0.05 reductions in blood glucose levels at a dosage of 400 mg/kg with decreases of 51.94% and 46.63%, respectively, compared to the positive control (64.02%). The central analgesic evaluation showed significant (p < 0.001) enhancements in tail-flick latency for the fraction (184.94%) and CF (170.51%) following 90 min. In the pain relief assay, NHF showed inhibition (64.33%, p < 0.001) followed by an aqueous fraction (57.35%). These pharmacological findings were supported by in silico analysis. Concerning activity, 5-(dimethylamino)-1- acid phenyl ester (−8.9 kcal/mol) and 9,9-dimethyl-9H-fluoren-3-ol (−8.4 kcal/mol) displayed the strongest binding affinity to AMPK. Additionally, 2,3-diphenyl-2-cyclopropen-1-one exhibited favorable interactions with α-amylase (−8.0 kcal/mol) and α-glucosidase (−8.3 kcal/mol). Similarly, the central analgesic effect correlated with the strong μ-opioid receptor affinity of s-Triazine, 2-amino-4-(piperidinomethyl)-4-piperidino (−8.8 kcal/mol). N-Methyl-N-(4-toluenesulfonyl)-benzamide (−8.6 kcal/mol) and s-Triazine derivative (−8.9 kcal/mol) demonstrated notable COX-1 and COX-2 inhibition potential. Overall, the findings indicate I. chinensis leaves as a promising source of bioactive compounds with significant antihyperglycemic and analgesic properties. Full article

Background/Objectives: Modern diabetes therapy extends beyond glycemic control and increasingly focuses on comprehensive risk reduction to prevent long-term complications, improve quality of life, and reduce premature mortality. Accordingly, modern therapeutic approaches address not only glucose metabolism but also cardiovascular, renal, and metabolic consequences of diabetes. Within this context, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a significant therapeutic class. In addition to their well-known effects on glycemic control and the metabolic-cardiovascular-renal axis, increasing evidence suggests that these agents may exert a range of pleiotropic effects and opening new therapeutic venues, discussed in this review. Methods: A narrative review of the literature was conducted using the PubMed, Scopus, and Google Scholar databases. Publications from 2014 and 2026 were screened using predefined keywords related to GLP-1 RAs and their potential effects across multiple physiological systems and diseases. Notably, more than 80% of the included studies were published between 2020 and 2026, reflecting the recent growth of research in this field. Results: GLP-1 RAs have been associated with beneficial effects across a wide range of conditions, including substance use disorders, mental health disorders, neurodegenerative diseases, obesity-related complications, liver disease, genitourinary disorders, osteoarthritis, and sleep apnea. While they are currently the most effective pharmacological agents for the treatment of obesity, they also significantly reduce hepatic steatosis and are associated with a decreased risk of developing hepatocellular carcinoma. Furthermore, they have also demonstrated positive effects against prostate cancer, polycystic ovary syndrome (PCOS), improved libido and fertility. Conclusions: GLP-1 RAs should no longer be regarded solely as antihyperglycemic agents. Instead, they represent a versatile therapeutic class with expanding clinical relevance across multiple medical disciplines. While current evidence is promising, further large-scale, well-designed clinical trials are required to define their full therapeutic potential. Full article

Background/Objectives: Erectile dysfunction (ED) affects up to 50% of men with type 2 diabetes mellitus (T2DM), yet the independent effects of oral antihyperglycemic medications on erectile function remain controversial. This study investigated associations between commonly prescribed antihyperglycemic medications and erectile function in Taiwanese men with T2DM. Methods: This cross-sectional study enrolled 242 Taiwanese men aged 18–80 years with T2DM. Erectile function was assessed using the International Index of Erectile Function–5 (IIEF-5). Participants were categorized by 12-month HbA1c patterns into well-controlled, variably controlled, and poorly controlled groups. Multiple linear regression models adjusted for demographics, metabolic parameters, and comorbidities examined medication–IIEF-5 associations. Results: The mean IIEF-5 score was 18.16 ± 5.68. None of the seven oral antihyperglycemic medication classes showed significant independent associations with IIEF-5 scores. However, glycemic control demonstrated a significant association with erectile function (F(2,192) = 3.390, p = 0.036), with well-controlled patients showing higher scores than poorly controlled patients (mean difference = 2.488, p = 0.032). Conclusions: In this cross-sectional study, better glycemic control was associated with improved erectile function in men with T2DM. No significant independent associations were observed between individual oral antihyperglycemic medication classes and erectile function after adjustment for glycemic control and other confounders. These findings suggest that glycemic management, rather than the independent effect of medication class, may be the primary determinant of erectile function in this population; however, causal inferences cannot be drawn from this cross-sectional design. Full article