Search Results (4,402)

Stress-induced premature senescence (SIPS) of endothelial cells can cause endothelial dysfunction. As a first-line antidiabetic agent, the specific role of metformin in SIPS has not yet been clarified. In this study, an in vitro SIPS model was induced by exposing human umbilical vein endothelial cells (HUVECs) to hydrogen peroxide (H₂O₂), and the effects of metformin on cell senescence, proliferation, migration, tube formation, and mitochondrial function were evaluated. Gene expressions altered by metformin were profiled via transcriptome sequencing. Specifically, the potential involvement of migrasome-mediated mitocytosis in metformin-driven effects was examined using confocal microscopy and siRNA-mediated silencing. The results showed that metformin significantly reduced SA-β-gal activity and restored the migration and tube-forming capacities of H₂O₂-induced senescent HUVECs. Moreover, metformin regulated mitochondrial dynamics, restored mitochondrial membrane potential, and attenuated intracellular oxidative stress. Notably, transcriptomic and functional analyses suggested that metformin enhanced migrasome formation and migrasome-mediated mitocytosis. Inhibition of migrasome formation by siTSPAN4 abolished the protective effect of metformin against SIPS. Collectively, these findings demonstrate that metformin alleviates early SIPS-associated changes in HUVECs and suggest that migrasome-mediated mitocytosis contributes to this protection by ameliorating mitochondrial dysfunction. This provides novel mechanistic insight into the vascular protective effects of metformin. Full article

Polycystic ovary syndrome (PCOS) is one of the most common metabolic–endocrine disorders affecting women of reproductive age and represents a significant public health concern due to its clinical heterogeneity. It is characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, and is frequently associated with hyperinsulinemia, obesity, dyslipidemia, chronic low-grade inflammation, and an increased risk of type 2 diabetes and cardiovascular disease. Conventional treatments, including combined oral contraceptives, metformin, and ovulation-inducing agents, primarily target symptoms and present limitations in efficacy, tolerability, and their ability to address underlying metabolic dysfunction. In this context, naturally derived bioactive compounds have emerged as promising complementary therapeutic strategies. Various phytochemicals exhibit antioxidant, anti-inflammatory, hypoglycemic, and reproductive axis-modulating effects by targeting key molecular pathways involved in insulin resistance, hyperandrogenism, and follicular dysfunction. Emerging preclinical and clinical evidence suggests that these compounds may improve metabolic, hormonal, and reproductive outcomes in women with PCOS. Full article

The bark of Myrica rubra (Lour.) Siebold & Zucc (M. rubra) is a natural remedy widely used in China and other Asian countries to treat tissue and bone injuries, burns, scalds, gastrointestinal ulcers, and diarrhea. Myricanol is an important ingredient in the bark of M. rubra. This review summarizes articles published over the past 26 years on the pharmacological effects and mechanisms of action of myricanol, aiming to advance research and applications of myricanol. Evidence shows that myricanol has multiple bioactive properties, including antioxidant, anticancer, anti-inflammatory, antimicrobial, antidiabetic, and antihyperlipidemic effects. Myricanol improves metabolic abnormalities in mice by activating the AMPK/SIRT1/PGC-1α signaling pathway. It also demonstrates significant anticancer, antioxidant, and anti-inflammatory actions, primarily by regulating Caspase and BCL-2 family proteins, inhibiting iNOS expression, scavenging free radicals, and interacting with Peroxiredoxin 5. Therefore, myricanol shows great potential for the treatment of cancer, metabolic abnormalities, and inflammatory bowel disease. Further research is needed to improve its bioavailability, confirm its pharmacological effects and mechanisms in vivo, and explore its pharmacokinetic properties and safety. Full article

Apitherapy is a complementary therapeutic approach based on the use of bee-derived products, particularly bee venom (BV), also known as apitoxin. Bee venom is a complex mixture of biologically active compounds, including peptides, enzymes, and biogenic amines, that exhibit diverse pharmacological activities. Major bioactive constituents such as melittin, apamin, adolapin, and phospholipase A2 have attracted increasing scientific interest due to their anti-inflammatory, antioxidant, antimicrobial, analgesic, and immunomodulatory properties. This review provides a comprehensive overview of the biological effects and therapeutic potential of bee venom in the management of chronic diseases, particularly diabetes, cancer, and neurological disorders. Evidence from experimental and clinical studies suggests that BV and its components can modulate multiple molecular pathways associated with oxidative stress, inflammation, apoptosis, and immune responses. These mechanisms contribute to potential benefits in glycemic control, tumor suppression, neuroprotection, and pain management. Additionally, bee venom has been investigated for its capacity to influence signaling pathways involved in cellular proliferation and survival, highlighting its potential as a complementary strategy in the treatment of complex diseases such as neurodegenerative disorders, including Parkinson’s and Alzheimer’s diseases. Despite these promising therapeutic effects, the clinical use of BV remains limited due to safety concerns, particularly the risk of allergic reactions, systemic toxicity, and anaphylaxis. Recent advances in drug delivery systems and nanotechnology may help improve the safety and efficacy of BV-based therapies by enabling targeted delivery and controlled dosing. Overall, bee venom represents a promising source of bioactive compounds with potential applications in translational and integrative medicine; however, further well-designed clinical trials and mechanistic studies are necessary to establish its safety, efficacy, and long-term therapeutic value. 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

Vitexin is a potent C-glycosyl flavone from mung bean coats with significant antioxidant properties, constrained by poor solubility and bioavailability. In this study, Nanovitexin (NV) was encapsulated within a biocompatible Alginate/Carboxymethyl Cellulose (Alg/CMC) matrix via a modified solvent evaporation technique assisted by chemical cross-linking. The optimized NV exhibited a mean dry particle size of 50–70 nm, high concentration (0.05–0.25 mg/mL), and stability (Zeta potential >30 mV). FT-IR analysis confirmed the successful entrapment via intermolecular interactions. Notably, NV exhibited enhanced activities compared to free vitexin (FV), showing superior DPPH scavenging (IC₅₀ of 115.38 μg/mL) versus FV (IC₅₀ of 226.06 μg/mL). Furthermore, NV demonstrated significantly enhanced in vitro antidiabetic potential, displayed no cytotoxicity towards HepG2 cells, and effectively protected against H₂O₂-induced oxidative stress. The Alg/CMC nanomatrix effectively improves vitexin bioactivity, suggesting promising potential for pharmaceutical and nutraceutical applications. Full article

Corn tortillas are consumed daily in Mexico. Alkaline extrusion is an alternative process that generates nixtamalized tortillas and preserves more bioactive compounds. Chickpea germination-extrusion may enhance the bioactive compound content. The aim was to characterize the physicochemical and antioxidant/antidiabetic properties of functional tortillas of alkaline-extruded blue corn (TC) with germinated (TG) or germinated-extruded (TGE) desi-chickpea. Likewise, the effect of simulated gastrointestinal digestion (SGD) on the bioaccessibility of bioactive compounds (phenolics, soluble protein, peptides, anthocyanins, and isoflavones) was estimated. Antioxidant capacity/cellular activity was determined by ORAC (AoxC) and in the Caco-2 cell line (CAA), while antidiabetic potential by α-amylase inhibition. The supplementation with processed chickpeas (TG/TGE) increased protein, ash, and isoflavone content (p < 0.05) compared with TC. SGD (%) released (p < 0.05) bioactive compounds from tortillas, and their bioaccessibility was among 34–70%; noticeably low phenolic bioaccessibility in TG/TGE. The AoxC was higher in TG/TGE (p < 0.05) compared with TC; in contrast, CAA was higher in TC, and both increased after SGD. TG depicted the lowest amylase inhibition; after SGD, the IC₅₀ values were 62–72-fold lower in the digests than in the tortillas. These results suggest that functional tortillas with processed chickpeas enhance nutraceutical potential. Full article

Background: Pyrroloquinoline quinone (PQQ), a naturally occurring redox cofactor with potent antioxidant and anti-inflammatory properties, has been shown to protect against cardiac injury. However, its therapeutic potential in diabetic cardiomyopathy (DCM) induced by Type 2 diabetes mellitus (T2DM) and the underlying mechanisms remain poorly understood. Methods: A T2DM mouse model was established via a high-fat diet and low-dose STZ. We investigated the cardioprotective effects of 12-week oral PQQ administration, assessing fasting blood glucose, oral glucose tolerance, cardiac function, myocardial histopathology, blood biochemistry, mitophagy, and NLRP3 inflammasome activation. In vitro experiments using AC16 cardiomyocytes exposed to palmitic acid and high glucose were also conducted. Results: Results showed PQQ significantly improved cardiac function, attenuated remodeling, and reduced proinflammatory cytokines in mice with T2DM, regulated key mitophagy-related proteins (Parkin, Beclin-1, LC3B-II, p62), and downregulated NLRP3 inflammasome pathway components (Caspase-1, NLRP3, IL-1β, IL-18). In vitro experiments demonstrated that PQQ reduced reactive oxygen species (ROS) production, improved mitochondrial membrane potential, promoted mitophagy, and inhibited NLRP3 inflammasome-mediated pyroptosis. Conclusions: PQQ alleviates DCM in mice with T2DM by improving mitochondrial quality control, promoting mitophagy, and subsequently inhibiting NLRP3 inflammasome-mediated pyroptosis, highlighting its potential as a promising therapeutic agent for T2DM-associated cardiomyopathy. Full article

The advanced glycation end products generated from protein glycation are associated with the development of diabetic complications. This study aimed to investigate the inhibitory mechanisms of isoliquiritigenin on protein glycation and compare its anti-glycation activity in PBS versus a macromolecular crowding environment. The results showed that in PBS, 500 μmol/L isoliquiritigenin showed an advanced glycation end product inhibition rate of 37.78%, outperforming aminoguanidine. Meanwhile, isoliquiritigenin inhibited the protein carbonylation process, reduced the generation of protein oxidation products, and inhibited the formation of β-crosslinking structures with a rate of 34.20%. Molecular docking results indicated that isoliquiritigenin bound to site I of bovine serum albumin, effectively blocked glycation reactions by occupying multiple arginine residues and contributed to stabilizing the secondary structure of bovine serum albumin. In addition, isoliquiritigenin exhibited significant hydroxyl radical scavenging and Fe²⁺-chelating abilities, achieving a 34.35% trapping efficiency for methylglyoxal. Isoliquiritigenin exerted its anti-glycation activity through multiple pathways, including scavenging free radicals, protecting protein structure, interacting with bovine serum albumin, and trapping methylglyoxal. However, in the crowding environment, the excluded volume effect and higher viscosity might lead to limited isoliquiritigenin binding to bovine serum albumin, reducing its inhibition of glycation and decreasing advanced glycation end product inhibition to 16.38%. This study realistically evaluated the inhibitory effects of isoliquiritigenin in complex crowding environments and provided a theoretical basis for isoliquiritigenin as a functional food ingredient for the prevention of diabetes complications. Future studies need to establish animal models to further explore its effects in vivo. Full article

Diabetic cardiomyopathy (DC) is a serious health issue. MicroRNA-155b expression dysregulation might be involved in the fibrotic cycle in DC. L-Arginine (l-arg) is reported to have a preferable impact on the cardiovascular system. We aimed to understand the pathogenesis of DC and to detect the potential protective effect of l-arg through modulation of apoptosis, inflammation, fibrosis, and miR-155b expression. This study comprised four groups of forty adult male rats (10 rats in each group): diabetics, l-arg diabetics, l-arg, and controls. Blood glucose, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), body weight, and cardiac hypertrophy index (HW/BW ratio) were assessed. Echocardiographic assessment of left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) was done. Expressions of toll-like receptor-4 (TLR4), pro-inflammatory interleukin 1 beta (IL-1β), interleukin 6 (IL-6), anti-inflammatory interleukins (IL-4, IL-13), apoptotic markers (bcl-2, bax) and microRNA-155b were measured by real-time PCR. Myocardial light, electron microscopic and morphometric studies were performed. Results showed a significant decrease in cardiac hypertrophy (HW/BW = 0.0030 ± 0.0002 mg/g), echocardiographic parameters (LVEF = 54.12 ± 1.628% and LVFS = 20.40 ± 0.541%), hemodynamic parameters (HR = 411.0 ± 9.684 bpm, SBP/DBP = 84 ± 4.998/60 ± 3.062 mmHg) and downregulation of the expression of IL-4, IL-13, IL- 1β, IL-6 and TLR4 in the l-arg diabetic group compared to diabetic rats. Additionally, restoration of normal appearance of most cardiac myofibrils, intact blood vessels, decreased cardiac fibrosis and upregulation of bax expression were observed. Expression of microRNA-155b increased by 0.007 for each gram increase in blood glucose (>1.45, it showed 100% specificity and 96.7% sensitivity). In conclusion, microRNA-155b upregulation is associated with enhancement of the transcription of inflammatory cytokines and apoptotic genes. L-arginine may be a useful protective strategy for DC through modulation of apoptosis, inflammation, and fibrosis, in addition to regulating the expression of miR-155b. Full article

Diabetes mellitus is a chronic and increasingly prevalent metabolic disorder characterized by persistent hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. Despite the availability of pharmacological agents that effectively manage blood glucose levels, many are associated with adverse effects, limited efficacy over time, and high costs. Consequently, there is growing interest in alternative therapies, especially those derived from traditional medicinal plants, that have long been employed in various cultures for managing diabetes. Recent advances in phytochemistry have identified bioactive plant secondary metabolites with promising antidiabetic properties. This review aims to provide a comprehensive overview of plant-derived compounds that exhibit inhibitory activity against key diabetes-related enzymes, including α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase-4 (DPP-4). These enzymes play critical roles in glucose metabolism and insulin signaling pathways. The review highlights the structural diversity of these natural inhibitors, their mechanisms of action, and their effectiveness in preclinical models. Understanding the molecular interactions and pharmacological profiles of these metabolites may facilitate the development of safer and more effective antidiabetic agents. Full article

Background: Type 2 diabetes mellitus (T2DM) represents a pressing global health challenge, underscoring the urgency of developing effective dietary interventions derived from natural resources. Zaojiaomi polysaccharide (ZJMP) from the endosperm of Gleditsia sinensis seeds (zaojiaomi), a traditional edible product, exhibits largely underexplored potential in T2DM management. Methods: In the present study, the antidiabetic effects and underlying mechanisms of ZJMP were investigated using a rat model of T2DM induced by a high-fat diet (HFD) combined with streptozotocin (STZ). Relevant biochemical indicators were detected, and histopathological examination was performed. The expression levels of key components of the TLR4/MyD88/NF-κB signaling pathway, as well as the inflammatory cytokines IL-6 and IL-1β in renal tissues, were further analyzed. Additionally, gut microbiota composition and the levels of short-chain fatty acids were determined. Results: ZJMP treatment significantly ameliorated hyperglycemia and dyslipidemia, elevated serum insulin levels, reduced intestinal mucosal permeability, and attenuated histopathological lesions in the heart, kidney, and pancreas of T2DM rats. Meanwhile, ZJMP notably alleviated renal inflammation by suppressing the production of IL-1β and IL-6, as well as inhibiting the TLR4/MyD88/NF-κB pathway. Furthermore, ZJMP administration effectively modulated gut microbiota composition and increased fecal concentrations of acetic acid and propionic acid. Conclusions: Collectively, these findings elucidate the novel bioactivity of ZJMP and highlight its potential as a promising functional food ingredient or dietary supplement for T2DM management. 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

Obesity is a complex, heterogeneous, chronic, and progressive disease, which correlates with an augmented risk of developing several comorbidities, including painful conditions, such as osteoarthritis. In this review, authors present for the first time the term meta-neuroinflammation for describing how the chronic, low-grade systemic inflammation, that occurs in obesity, may trigger oxidative stress and neuroinflammatory processes. Both the peripheral and the central nervous system are involved in neuroinflammation, leading to central sensitization and pain chronification, which leads to the observed increased incidence in obese patients of chronic pain syndromes, particularly osteoarthritis, low back pain, fibromyalgia, headache, and diabetic peripheral neuropathy. Possible mechanisms by which obesity may cause meta-neuroinflammation include adiposopathy, gut microbiota dysbiosis, and compromised integrity of blood–brain barrier, which could explain obesity-related depressive and neurodegenerative disorders. Preclinical data suggest the meta-neuroinflammation as a potential target of treatment in obese patients with degenerative joint disease. Based on these observations, targeted therapeutic strategies may include systemic administration of ultramicronized palmitoylethanolamide (um-PEA), well known for its neuroprotective, anti-neuroinflammatory, and analgesic actions, and comicronized PEA–rutin and hydroxytyrosol to restore intestinal eubiosis, with beneficial effects on body weight and mental disorders. Finally, Adelmidrol, as a PEA congener, could be considered for mitigating intra-articular meta-neuroinflammation in knee osteoarthritis. Full article

Mesenchymal stromal cells (MSCs) are multipotent cells characterized by their regenerative capacity and strong immunomodulatory properties. In recent years, MSC-based therapy has attracted significant attention as a potential treatment for a wide range of immune-mediated and degenerative diseases. The therapeutic effects of MSCs are primarily mediated through paracrine signaling and secretion of cytokines that regulate immune responses and promote tissue repair. This review focuses on five key cytokines involved in MSC immunomodulation: interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α), and interleukin-1 beta (IL-1β). These cytokines interact within a complex signaling network that allows MSCs to suppress excessive inflammation and restore immune balance. The role of MSC therapy is examined in several clinically relevant conditions, including systemic lupus erythematosus, systemic sclerosis, ischemic stroke, spinal cord injury, diabetes mellitus, and female infertility. Across these diseases, MSCs demonstrate the ability to inhibit pro-inflammatory immune cell activity, promote regulatory immune phenotypes, reduce oxidative stress, and stimulate regeneration through the secretion of growth factors and extracellular vesicles. Despite promising experimental and early clinical findings, several limitations remain, including variability in MSC sources, limited cell survival after transplantation, and the need for optimized dosing strategies. Overall, MSC therapy represents a multifunctional therapeutic approach combining immunomodulation, anti-inflammatory activity, and regenerative support. Further research is required to better understand cytokine interactions, improve standardization of MSC-based treatments, and enhance clinical efficacy across diverse pathological conditions. Full article