Search Results (130)

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

Diabetes mellitus (DM) is a global health challenge marked by chronic hyperglycemia, which can result in complications such as diabetic cardiomyopathy. Sitagliptin, an oral anti-hyperglycemic drug, has demonstrated efficacy in alleviating cardiovascular complications associated with DM. This study explored the impact of Sitagliptin’s potential as a therapeutic agent, functioning not only to control blood sugar levels but also to enhance vascular health and strengthen cardiac resilience in diabetes. The investigation focused on alterations in the vascular endothelial growth factor (VEGF) and its receptor-1 (FLT-1) signaling pathways, as well as its potential to suppress inflammation and oxidative stress. A number of rats received a single dose of streptozotocin (STZ) 55 mg/kg (i.p.) to induce DM. Sitagliptin was administered orally (100 mg/kg/90 days) to normal and diabetic rats, after which samples were collected for investigation. Sitagliptin significantly mitigated weight loss in diabetic rats. Its administration significantly reduced blood glucose levels and improved serum troponin I and CK-MB levels. Heart sections from diabetic rats showed a marked increase in mTOR, VEGF, and FLT-1 immune reaction, while sitagliptin-treated diabetic rats’ heart sections showed moderate immune reactions. Sitagliptin’s protective effect was also associated with reduced inflammation, and apoptotic markers. In conclusion, Sitagliptin is suggested to offer beneficial effects on the vascular health of cardiac blood vessels, thereby potentially reducing myocardial stress in diabetic patients. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Obesity is considered a global pandemic. In Mexico, 7/10 adults, 4/10 adolescents, and 1/3 children are overweight or obese, and it is estimated that 90% of cases of type 2 diabetes (T2D) are attributable to these pathologies. Visceral adipose tissue (VAT) presents increased lipolysis, lower insulin sensitivity, and greater metabolic alterations. Glucagon-like peptide-1 (GLP-1) is a polypeptide incretin hormone that stimulates insulin secretion dependent on the amount of oral glucose consumed, reduces plasma glucagon concentrations, slows gastric emptying, suppresses appetite, improves insulin synthesis and secretion, and increases the sensitivity of β cells to glucose. Liraglutide is a synthetic GLP-1 analog that reduces VAT and improves the expression of Glucose transporter receptor type 4 (GLUT 4R), Mitogen-activated protein (MAP kinases), decreases Fibroblast growth factor type β (TGF-β), reactivates the peroxisome proliferator-activated receptor type ɣ (PPAR-ɣ) pathway, and decreases chronic inflammation. Currently, there are many studies that explain the decrease in VAT with these medications, but there are no studies that compare the decrease in patients with obesity and prediabetes vs. obesity and type 2 diabetes to know which population obtains a greater benefit from treatment with this pharmacological group; this is the reason for this study. The primary objective was to compare the difference in the determination of visceral adipose tissue in people with obesity and type 2 diabetes vs. obesity and prediabetes treated with liraglutide. Methods: A quasi-experimental, analytical, prolective, non-randomized, non-blinded study was conducted over a period of 6 months in a tertiary care center. A total of 36 participants were divided into two arms; group 1 (G1: Obesity and prediabetes) and group 2 (G2: Obesity and type 2 diabetes) for 6 months. Inclusion criteria: men and women ≥18 years with type 2 diabetes, prediabetes, and obesity. Exclusion criteria: Glomerular filtration rate (GFR) < 60 mL/min/1.73 m² elevated transaminases (>5 times the upper limit of normal), and use of non-weight-modifying antidiabetic agents. Conclusions: No statistically significant difference was found in the decrease in visceral adipose tissue when comparing G1 (OB and PD) with G2 (OB and T2D). When comparing intragroup in G2 (OB and T2D), greater weight loss was found [(−3.78 kg; p = 0.012) vs. (−3.78 kg; p = 0.012)], as well differences in waist circumference [(−3.9 cm; p = 0.049) vs. (−3.09 cm; p = 0.017)], and glucose levels [(−1.75 mmol/L; p = 0.002) vs. (−0.56 mmol/L; p = 0.002)], A1c% [(−1.15%; p = 0.001) vs. (−0.5%; p = 0.000)]. Full article

Type 2 diabetes mellitus remains a critical global health challenge, driving the pursuit of novel therapeutic strategies. This study investigated the anti-diabetic efficacy of the peptide 1CBR, derived from sodium caseinate hydrolysate, administered orally at 25 mg/kg/day to db/db mice over a 4-week period. Glucose tolerance was evaluated via oral glucose tolerance tests (OGTT), while plasma dipeptidyl peptidase-IV (DPP-IV) activity, glucagon-like peptide-1 (GLP-1), and insulin concentrations were quantified using enzyme-linked immunosorbent assays (ELISA). Two bioactive peptides, GPFPLPD and APDSGNFR, were isolated and characterized, exhibiting half-maximal inhibitory concentrations (IC₅₀) of 99.12 µM and 73.07 µM for DPP-IV inhibition, respectively, and both significantly stimulated GLP-1 secretion in enteroendocrine cells in vitro. Pharmacokinetic analysis in Sprague–Dawley rats demonstrated oral bioavailability of 11.28% and 19.12% for these peptides, surpassing typical expectations for peptide-based agents. Collectively, these results provide compelling evidence that 1CBR-derived peptides exert glucose-lowering effects through the dual mechanisms of DPP-IV inhibition and GLP-1 stimulation, combined with favorable oral absorption profiles. These findings underscore the potential of 1CBR peptides as promising candidates for development into nutraceuticals or pharmaceutical agents for diabetes management. Full article

Background and Aims: Colorectal cancer (CRC) remains the third most common cancer worldwide and a leading cause of cancer-related death. Chemoprevention through widely used pharmaceutical agents has garnered increasing interest due to its potential cost-effectiveness and accessibility. This review summarizes current evidence from observational studies, randomized controlled trials, and meta-analyses on the association between commonly prescribed medications and CRC incidence and survival, with particular emphasis on low-dose aspirin and oral anticoagulants (OACs). Scope: Aspirin is the most extensively studied agent, with substantial evidence supporting its protective effect on CRC-specific survival, particularly in long-term users, those with COX-2 overexpression, or PIK3CA mutations. OACs have recently gained attention due to their association with increased gastrointestinal bleeding, which may facilitate earlier CRC detection. While emerging evidence suggests a possible survival benefit through this mechanism, data remain heterogeneous and affected by methodological challenges such as lead-time bias. Metformin is associated with improved CRC outcomes, primarily in patients with type 2 diabetes, though its direct anti-tumor potential remains under investigation. Corticosteroids, statins, and beta-blockers have both limited and inconclusive evidence. Finally, recent studies on vitamin D, calcium, and folic acid suggest inconsistent associations, often confounded by lifestyle factors or underlying comorbidities. Conclusions: While promising, chemoprevention strategies require further validation in well-designed, mechanistically informed studies that account for confounding variables, treatment duration, and tumor biology. Personalized prevention—guided by genetic, molecular, and clinical risk factors—represents a promising path forward. Full article

Background: Dulaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist administered subcutaneously once a week, developed through recombinant DNA technology, and prescribed as an add-on to diet and exercise for managing type 2 diabetes mellitus in adults. In several clinical trials, once-weekly dulaglutide has demonstrated reductions in cardiovascular risk associated with diabetes, as well as improvements in glycemic control and weight reduction. The scope of this study was to evaluate the effect of dulaglutide 1.5 mg on glycemic control, weight management, and LDL-cholesterol levels in patients with uncontrolled type 2 diabetes mellitus. Methods: We retrospectively reviewed the medical records of 55 patients with inadequately controlled type 2 diabetes mellitus who were on oral antidiabetic agents and insulin, and who were additionally treated with dulaglutide 1.5 mg. We monitored fasting plasma glucose and glycated hemoglobin (HbA1c) at baseline and at 6, 12, and 24 months after initiating dulaglutide treatment. Weight, body mass index, and LDL-cholesterol were assessed at baseline and after 24 months of dulaglutide therapy. Results: Treatment with dulaglutide resulted in significant improvements in fasting plasma glucose and HbA1c after 6 months (p < 0.001), 12 months (p < 0.001), and 24 months (p < 0.001). A significant weight reduction was observed after 24 months of dulaglutide therapy (−3.3 kg; p < 0.001). In addition, we observed a significant reduction in LDL-cholesterol after 24 months (p < 0.001). Conclusions: Our data demonstrate that dulaglutide 1.5 mg significantly improves glycemic control, reduces body weight, and lowers LDL-cholesterol in Romanian patients with inadequately controlled type 2 diabetes. Full article

Background: Much research has demonstrated that there is a relation between depression and chronic diseases. Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases, and it is an expanding global health problem. This study aims to explore the relationship between glycemic control (GC), antidiabetic agents, and depression in T2DM, focusing on how depression affects treatment adherence and GC. Methods: This prospective study included 250 patients with T2DM. Demographic information and laboratory results were obtained from the patients as well as from the hospital’s laboratory system. Beck’s Depression Inventory (BDI) scores, GC indicator HbA1c levels, and antidiabetic agents used by the patients were compared. Results: Upon analyzing the findings, we found a statistically significant positive correlation between the severity of depression and HbA1c levels (p < 0.001). Additionally, no significant relationship was observed between depression and the use of oral antidiabetic medications, except for metformin. However, a significant association between depression and insulin use was found even in patients with good GC (p < 0.001), regardless of whether HbA1c was high. Conclusions: Regardless of the type of antidiabetic treatment, diabetic patients receiving intensive insulin therapy, whether they have good or poor GC, should be carefully evaluated for depressive symptoms. Appropriate psychiatric support should be provided to help achieve GC and enhance their quality of life. Our study is the first to emphasize the importance of close monitoring for diabetic patients using insulin, even those with good GC. Understanding these interactions may improve disease management, patient outcomes, and quality of life. Full article

Atherosclerotic cardiovascular disease is a major complication of diabetes, whose progression is significantly accelerated by hyperglycemia. Imeglimin, a novel oral antidiabetic agent, has demonstrated efficacy in glucose control; however, its role in diabetes-related cardiovascular complications has not yet been fully explored. This study aimed to investigate the effects of imeglimin on foam cell formation and atherosclerosis in the context of diabetes. THP-1 macrophages were treated with oxidized low-density lipoprotein (LDL) and high glucose to induce foam cell formation in vitro. Additionally, ApoE^−/− mice with streptozotocin-induced diabetes were used to determine the effects of imeglimin in vivo by analyzing metabolic parameters and atherosclerotic plaque formation. Imeglimin inhibited macrophage-derived foam cell formation by promoting the expression of ATP-binding cassette transporters (ABC) A1 and ABCG1 and downregulating the expression of CD36. The effects of imeglimin on ABCG1 and CD36 expression regulation was mediated by AMPK. In diabetic ApoE^−/− mice, imeglimin reduced the atherosclerotic plaque area, decreased fasting glucose and LDL cholesterol levels, and upregulated ABCG1 expression in the liver and aorta. These findings suggest that imeglimin may have a preventive effect on foam cell formation and a therapeutic role in atherosclerosis progression in diabetic conditions. Full article

Diabetes mellitus (DM) is a major risk factor for cardiovascular disease, including heart failure (HF). A high proportion of DM patients eventually require cardiac surgery. While the traditional approach to DM therapy focuses on tight glucose control with insulin and oral hypoglycemic agents, novel antidiabetic drugs have emerged over the past two decades that offer not only improved glycemic control but also cardiovascular and renal protection, such as benefits in HF management. The aim of this review is to examine and evaluate the perioperative risk and benefits of novel antidiabetic agents in HF treatment for both DM and non-DM patients undergoing cardiac surgery. We specifically studied glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 (DPP-4) inhibitors, and sodium–glucose cotransporter 2 inhibitors (SGLT2is). Although studies on novel antidiabetic therapy in cardiac surgeries were limited, the results showed all three agents to be safe for use in the perioperative period, with SLGT2i demonstrating the most benefits in HF management for those with or without DM and kidney impairment undergoing cardiac surgery. Future research on larger study populations and using a more rigorous study design is necessary in bridging current knowledge to improve patient outcomes. Full article

Thymoquinone (TQ), a bioactive compound derived from black cumin seeds, is renowned for its potent anti-obesity and anti-diabetic properties. Due to the stability challenges of TQ, it has predominantly been utilized in oil formulations. This study aimed to enhance the stability of TQ and investigated the impact of consuming insoluble fiber from black cumin seeds on restoring antioxidant function compromised by diabetes and improving hyperglycemia management. We evaluated the restorative effects of a 35-day administration of black cumin seed extract (BCS) on antioxidant function impaired by streptozotocin (STZ)-induced diabetes, alongside structural and functional alterations in the pancreas, liver, and kidneys. The results demonstrated significant improvements in organ weight, particularly in pancreatic tissue. Moreover, BCS administration markedly suppressed the expression of key genes associated with pancreatic dysfunction and damage, including caspase-3, transforming growth factor-beta 1 (TGF-β1), and interleukin-1 beta (IL-1β). Through oral glucose tolerance tests (OGTTs), BCS was found to effectively regulate chronic hyperglycemia and exhibit potential for managing acute hyperglycemia. These findings suggest that BCS not only addresses both glycemic and non-glycemic complications of diabetes but also offers a safe, long-term solution. Consequently, BCS emerges as a promising therapeutic agent for hyperglycemia management, including in prediabetic stages. Full article

Currently, there are several drugs used for the treatment of type 2 diabetes (T2D); however, all of them have adverse effects. Benzothiazoles have a broad spectrum of biological activities such as antidiabetic. This study aimed to evaluate in silico and in vivo two series of 2-aminobenzothiazole derivatives linked to isothioureas (3a–w) or guanidines (4a–z) for the treatment of T2D. The ADMET properties were determined in silico, from which it was possible to select nine compounds (two isothioureas and seven guanidines), and, with molecular docking, it was shown that compounds methyl (E)-N′-(benzo[d]thiazol-2-yl)-N-methylcarbamimidothioate (3b) and 2-(benzo[d]thiazol-2-yl)-1,3-di-tert-butylguanidine (4y) showed a high affinity for PPARγ (ΔG = −7.8 and −8.4 kcal/mol, respectively). In vivo, the LD50 value was estimated in rats based on OECD Guideline 425, being >1750 mg/kg for both compounds. The pharmacological effect of 3b and 4y was evaluated in the T2D rat model, showing that after oral administration in an equimolar ratio to pioglitazone (15 mg/kg) for 4 weeks, both compounds were able to reduce blood glucose levels (<200 mg/dL) and improve the lipid profile. Therefore, 3b and 4y could be used in the future as antidiabetic agents. Full article

Diabetes is a complex global healthcare burden involving multiple organ systems with its prevalence on the rise. SGLT2 inhibitors enhance glucose excretion. The objective of our literature review was to determine the association between cutaneous adverse drug reactions (CADRs) and the use of SGLT2 inhibitors. We collected data on CADRs related to the use of SGLT2 inhibitors from all available published articles and studied their details to understand the patterns of their association. PubMed, Cochrane, Google, and Embase were searched for relevant articles. A total of 37 papers were included and studied. Most articles were case reports followed by pharmacovigilance studies, case series, and reviews. The cutaneous findings ranged from benign eruptions to severe reactions. The available literature suggests a strong link between the use of SGLT2 inhibitors and Fournier’s gangrene/necrotizing fasciitis. T2DM patients using SGLT2 inhibitors have also developed fixed drug eruptions, drug-induced pruritus, and Sweet syndrome/acute febrile neutrophilic dermatosis, among other skin lesions. We found that SGLT2 inhibitors present a risk of developing CADRs. Raising awareness among healthcare providers regarding CADRs to SGLT2 inhibitors can reduce complications, minimize hospitalizations, and improve patient care in the vulnerable population of diabetes patients. Full article

Glandirana is a genus of frogs that includes G. rugosa, G. emeljanovi, G. minima, G. tientaiensis, G. susurra, G. nakamurai and G. reliquia. These frogs produce antimicrobial peptides (AMPs), which are endogenous antibiotics that possess antibacterial, antifungal, antiviral and anti-endotoxin activity and help keep the hosts free from infections. In these activities, microbial death is promoted by membranolytic mechanisms that are mediated by the cationic charge and amphiphilic α-helical structures of these peptides. In general, these peptides are selective for microbes, showing low levels of hemolytic and cytotoxic activity, as well as possessing other biological activities, including anticancer, antioxidative and insulinotrophic action. In this review, a brief overview of AMPs with a focus on those from amphibians is provided, along with the phylogeny and nomenclature of frogs and AMPs from the Glandirana genus. This review then provides a comprehensive, in-depth description of the antimicrobial and other biological activities of all AMPs produced by known frogs of the Glandirana for the period 1994 to 2024. This description includes a detailed discussion of the structure/function relationships and mechanisms involved in the membrane interactions that drive these biological activities, with comparisons between AMPs from the same frog and between frogs across the genus. Based on their biological properties, AMPs from frogs of the Glandirana genus have been proposed for investigation as potential therapeutic agents, such as in the treatment of cancers and diabetes, as well as antimicrobial agents in areas, including crop protection, the food industry and oral hygiene. Full article

Cannabis sativa L. contains numerous compounds with antioxidant and anti-inflammatory properties, including the flavonoids and the cannabinoids, particularly Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoids have an effect on the endocannabinoid system (ECS), a cellular communication network, and are, hence, widely studied for medical applications. Epidiolex^®, a 99% pure oral CBD extract, has been approved by the FDA for the treatment of epilepsy. Nabiximols (Sativex) is an oromucosal spray containing equal volume of THC and CBD, and it is commonly used as an add-on treatment for unresponsive spasticity in multiple sclerosis (MS) patients. Several in vitro and in vivo studies have also shown that cannabinoids can be used to treat various types of cancer, such as melanoma and brain glioblastoma; the first positive clinical trials on the anticancer effect of a THC:CBD blend with temozolomide (TMZ) in the treatment of highly invasive brain cancer are very promising. The cannabinoids exert their anticancer properties in in vitro investigations by the induction of cell death, mainly by apoptosis and cytotoxic autophagy, and the inhibition of cell proliferation. In several studies, cannabinoids have been found to induce tumor regression and inhibit angiogenic mechanisms in vitro and in vivo, as well as in two low-numbered epidemiological studies. They also exhibit antiviral effects by inhibiting ACE2 transcription, blocking viral replication and fusion, and acting as anti-inflammatory agents; indeed, prior CBD consumption (a study of 93,565 persons in Chicago) has also been associated with a much lower incidence of SARS-CoV-2 infections. It is postulated that cannabis extracts can be used in the treatment of many other diseases such as systemic lupus erythematosus, type 1 diabetes, or various types of neurological disorders, e.g., Alzheimer’s disease. The aim of this review is to outline the current state of knowledge regarding currently used medicinal preparations derived from C. sativa L. in the treatment of selected cancer and viral diseases, and to present the latest research on the potential applications of its secondary metabolites. Full article