Search Results (1,048)

Jania rubens (J. rubens), a Mediterranean red seaweed, is rich in bioactive compounds with potential medicinal applications. This study investigates the therapeutic potential of Lebanese J. rubens through in vitro evaluation of its anti-diabetic, anti-coagulant, anti-inflammatory and anti-hemolytic activities. Various extracts were prepared and characterized using GC-MS and HPLC. Biological activities were assessed through α-amylase inhibition assays, effects on prothrombin time and partial thromboplastin time, anti-inflammatory activity and anti-hemolytic activity. Significant α-amylase inhibition was observed with dichloromethane/methanol and lipid extracts, comparable to acarbose. All types of extracts prolonged PT and PTT, with the lipid extract showing the strongest effect at higher concentrations. Additionally, dichloromethane/methanol extracts exhibited potent anti-hemolytic activity. Moreover, all extracts showed strong anti-inflammatory activity, achieving levels of inhibition of heat-induced BSA denaturation comparable to diclofenac. Characterization revealed 11 amino acids in the protein extracts, and significant fatty acids in the lipid profile. The crude extracts contained diverse compounds, including flavonoids, aldehydes, diterpenoids, terpenoids, fatty acids, and sterol esters, which may contribute to the observed biological activities. These results highlight J. rubens as a potential reservoir of bioactive compounds with promising in vitro activities related to diabetes, thrombotic disorders, inflammation, and oxidative stress. Further research is needed to isolate the active compounds, validate their efficacy in vivo, assess safety, and elucidate the underlying mechanisms. Full article

Diabetes mellitus continues to impose a substantial global health burden, underscoring the need for therapeutic systems capable of achieving precise, adaptive, and patient-friendly glycemic control. Conventional diabetes treatments, including repeated insulin injections and oral hypoglycemic agents, are often constrained by non-physiological drug release, poor adherence, systemic side effects, and the persistent risk of hypoglycemia. In this context, glucose-responsive nanomedicine has emerged as a promising platform for next-generation diabetes therapy by enabling self-regulated and glucose-triggered delivery of insulin and other antidiabetic agents. This review highlights recent advances in glucose-responsive nanomedicine, focusing on the principal sensing mechanisms, including glucose oxidase-based, phenylboronic acid-based, and lectin-mediated systems, as well as the nanoscale carriers engineered to support them, such as polymeric nanoparticles, nanogels, micelles, liposomes, and hybrid nanostructures. These smart platforms offer significant potential to improve drug stability, enhance targeting efficiency, reduce dosing frequency, and more closely mimic endogenous insulin secretion. The review further examines their emerging role in precision diabetes care, particularly in combination with continuous glucose monitoring technologies, wearable devices, and closed-loop therapeutic systems. Despite notable progress at the preclinical level, important barriers to clinical translation remain, including challenges related to biocompatibility, long-term safety, reproducibility, scalable manufacturing, and regulatory approval. Collectively, glucose-responsive nanomedicine represents a rapidly advancing and clinically relevant field with the potential to redefine diabetes management through intelligent and personalized therapeutic strategies. This review provides a focused overview of current developments, key translational challenges, and future directions toward clinical implementation. Full article

Chronic diseases and aging-related disorders are driven by interconnected mechanisms, including oxidative stress, low-grade inflammation, metabolic dysregulation, and glycation. Targeting these overlapping pathways remains a major challenge for conventional single-target therapeutics. In this context, endophytic fungi have emerged as a promising source of bioactive metabolites with multi-target pharmacological potential. This review provides a mechanistic overview of endophyte-derived metabolites, including alkaloids, terpenoids, polyketides, and phenolic compounds, with a focus on their ability to modulate key signaling pathways such as NF-κB, Nrf2, PI3K/Akt, AMPK, and the AGE–RAGE axis. Evidence from experimental studies suggests that these metabolites exhibit anticancer, anti-inflammatory, antioxidant, and metabolic regulatory effects through coordinated modulation of cellular signaling networks. Several endophyte-derived metabolites also possess antimicrobial activity against bacterial and fungal pathogens and may represent a promising source of novel anti-infective agents. Their ability to modulate host immune responses and microbial-associated signaling pathways further highlights their relevance for antimicrobial discovery and microbiome-based therapeutic strategies. Particular attention is given to pathway-level convergence in chronic diseases, including cancer, diabetes, and inflammation-associated disorders, as well as their relevance to aging and health span. The pharmacological potential of these compounds is discussed alongside key limitations, including issues related to bioavailability, reproducibility, and translation into clinical applications. Overall, endophytic fungal metabolites represent a structurally diverse and mechanistically rich resource for the development of multi-target therapeutic strategies. Future integration of metabolomics, genome mining, and advanced disease models will be essential to bridge the gap between experimental findings and clinical application. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance, pancreatic β-cell dysfunction, and dysregulated glucose and lipid metabolism. Sustained hyperglycemia and hyperlipidemia promote excessive reactive oxygen species (ROS) production, antioxidant defense depletion, and chronic low-grade inflammation, thereby aggravating insulin signaling impairment, β-cell injury, and diabetes-related complications. Although current glucose-lowering therapies have improved glycemic control, weight management, and cardiorenal outcomes, oxidative stress and inflammation remain incompletely addressed in many individuals with T2DM. Curcumin, a natural polyphenol derived from Curcuma longa L., exhibits antioxidant, anti-inflammatory, lipid-regulating, insulin-sensitizing, and tissue-protective activities. Evidence suggests that curcumin may alleviate T2DM-associated oxidative stress by suppressing ROS generation, reducing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, modulating the advanced glycation end-product/receptor for advanced glycation end-product (AGE/RAGE) axis, activating nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) signaling, preserving mitochondrial homeostasis, and protecting β-cells. It may also inhibit nuclear factor-κB (NF-κB) and mitogen-activated protein kinase/c-Jun N-terminal kinase (MAPK/JNK) signaling, decrease pro-inflammatory cytokines and C-reactive protein (CRP), improve metabolic tissue inflammation, and attenuate gut-derived inflammation by regulating gut microbiota and intestinal barrier function. However, current clinical evidence mainly supports modest improvements in metabolic, inflammatory, oxidative stress-related, and selected complication-related biomarkers rather than definitive disease-modifying outcomes. Moreover, formulation heterogeneity, low bioavailability, limited pharmacokinetic reporting, and insufficient long-term endpoint data remain major translational barriers. This review summarizes the molecular mechanisms, clinical evidence, formulation-dependent interpretation, safety considerations, and translational limitations of curcumin as a candidate adjunctive intervention for T2DM, rather than as a replacement for evidence-based antidiabetic therapy. Full article

Several studies have suggested potential mechanisms through which Sutherlandia frutescens exerts antidiabetic effects, yet much of its therapeutic potential remains unexplored. This study aimed to provide greater insights into the antidiabetic capabilities and limitations of S. frutescens through the use of a comprehensive in vitro screening platform incorporating target-directed assays with automated image cytometry and analysis, where relevant. The antidiabetic effects of a crude hot aqueous extract of S. frutescens were assessed across well-characterised targets representing prominent hallmarks of diabetes: postprandial hyperglycaemia, insulin sensitivity, β-cell dysfunction, chronic inflammation and adipose tissue dysfunction. The findings revealed S. frutescens as a multicomponent therapeutic, with its individual target activities being relatively subtle and a few appearing novel. Notably, however, S. frutescens inhibited multiple targets relevant to postprandial hyperglycaemia—including carbohydrate digestion (29.1% and 26.4% inhibition for sucrose and maltose, respectively, at 500 µg/mL), intestinal glucose uptake in Caco-2 cells (between 9.51% and 20.92% reduction from 100 to 500 µg/mL) and protein glycation (23.2% inhibition at 200 µg/mL)—activities not previously documented in vivo. Glucose consumption in C3A hepatocytes showed a dose-dependent increase in glucose consumption from 12.5 to 100 µg/mL. Glucose consumption was reduced in palmitic acid-induced insulin-resistant L6 skeletal muscle cells from 100% to 69.57%, while 50 µg/mL S. frutescens restored it to 97.84%. S. frutescens also enhanced INS-1 β-cell survival under oxidative stress at concentrations as low as 12.5 µg/mL. The integration of automated image cytometry and analysis provides a novel approach with which to characterise its antidiabetic properties and elucidate its potential molecular mechanisms. Overall, S. frutescens is shown to impact several interrelated mechanisms simultaneously, suggesting that the coordinated modulation of multiple pathways may contribute to its overall biological activity. Whether these effects are additive or synergistic remains to be determined. Full article

Astragalus species have long been recognized for their pharmacological relevance, yet the antidiabetic properties of Astragalus cruciatus Link (Ac) remain poorly explored. This study aimed to investigate the antidiabetic potential of A. cruciatus Link and to elucidate possible underlying mechanisms. The ethanolic extract of Ac (AcEE) was prepared and analyzed for phenolic and flavonoid content. Antioxidant activity was assessed through a series of in vitro assays. The in vitro inhibition of α-amylase and α-glucosidase was assessed, followed by molecular docking to probe ligand-enzyme interactions. LC-ESI-MS analysis revealed a polyphenol-rich profile, with rutin (953.54 µg/g extract) and quinic acid (797.18 µg/g of extract) identified as main compounds. The AcEE showed significant inhibitory activity against both α-amylase and α-glucosidase (IC₅₀ = 239.30 ± 7.40 and 192.60 ± 15.51 μg/mL, respectively). Moreover, low cytotoxic effects were observed in hepatic cell lines. Computational analysis revealed stable interactions between rutin and both enzymes (−12.935 and −8.073 Kcal/mol, respectively). Network pharmacology revealed that AcEE may modulate key targets, including IL-6, TNF-α, IL-1β, Akt-1, STAT3, EGFR, and INSR as well as pathways related to insulin resistance, AGE-RAGE, and inflammation. These findings suggest that AcEE exerts significant antidiabetic effects through multitarget modulation, highlighting its potential as a natural therapeutic agent for T2DM. Full article

Background/Objective: Cinnamaldehyde (CA) is a naturally occurring bioactive compound derived from the leaves, bark, roots, and flowers of the Chinese medicinal plant Cinnamomum cassia. It exhibits a broad spectrum of pharmacological properties, encompassing antioxidant, antibacterial, anti-diabetic, antifungal, and anticancer activities. Notably, it has shown potential therapeutic benefits in the management of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). Ochratoxin A (OTA), a common contaminant found in foods such as cereals, coffee, and raisins, is also present in traditional Chinese medicinal materials, including Astragalus and liquorice. T2DM and NAFLD share intertwined pathophysiological pathways, including insulin resistance, dyslipidaemia, chronic low-grade inflammation and oxidative stress, with insulin resistance serving as the common pathological hub for both conditions. Consequently, they frequently co-occur and exacerbate each other. OTA exerts dual-targeted toxicity to the pancreas and liver, which may synergistically drive the development of the comorbidity of T2DM and NAFLD. These two processes are mutually causal and together constitute the pathological basis of metabolic comorbidity. Methods: Network toxicology employs toxicological data, gene expression, and protein–protein interaction (PPI) networks to predict the targets of toxins, while network pharmacology, based on systems biology principles, reveals how drugs exert regulatory effects through multiple targets and pathways. In this study, we employed an integrated network toxicology and network pharmacology approach to jointly decipher the potential mechanisms by which CA intervenes in OTA-induced comorbid T2DM-NAFLD. First, a network toxicology approach was employed to preliminarily screen for core toxicological targets responsible for OTA’s pathogenicity. Subsequently, network pharmacology was used to identify potential targets of CA-mediated intervention in the disease. Finally, the common overlap among the CA intervention targets, OTA toxicity targets, and disease targets was defined as the final set of potential targets for CA-mediated intervention in OTA-induced T2DM-NAFLD comorbidity. A PPI network was constructed using the STRING database, and topological analysis was performed with Cytoscape. Core targets were selected using the median values of six parameters—betweenness centrality, closeness centrality, degree centrality, eigenvector centrality, LAC (local average connectivity) score, and network centrality—as cut-off thresholds, and the top 10 key genes were further identified using the cytoHubba plugin. Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via the DAVID database, and the results were visualized on the CNSknowall platform. Lastly, molecular docking of the core targets was performed using the CB-DOCK2 platform to validate binding affinity. Results: Based on an integrated analysis of network toxicology, network pharmacology, and molecular docking, 10 key targets were systematically identified. These may serve as potential mediators of cinnamaldehyde in the treatment of OTA-induced T2DM-NAFLD comorbidity. Among these, six targets—albumin (ALB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), interleukin-6 (IL-6), tumor necrosis factor (TNF), actin beta (ACTB), and estrogen receptor 1 (ESR1)—possess crystal structures amenable to molecular docking. KEGG enrichment analysis revealed that CA and OTA jointly participate in key pathological processes such as the cancer pathway, the lipid and atherosclerosis pathway, the advanced glycation end-products–receptor for advanced glycation end-products (AGE-RAGE) signaling pathway, the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway, the TNF signaling pathway, and the interleukin-17 (IL-17) signaling pathway. OTA exacerbates inflammatory responses, impairs insulin signaling, promotes hepatic steatosis, and disrupts systemic metabolic homeostasis, ultimately contributing to T2DM-NAFLD comorbidity. Conversely, cinnamaldehyde counteracts these pathological processes through multiple mechanisms, including antioxidant and anti-inflammatory effects as well as regulation of glucose and lipid metabolism, thereby restoring metabolic homeostasis. Conclusions: This study has preliminarily identified the toxicological targets of OTA and the potential intervention targets of CA, offering new avenues for preventing and intervening in OTA-induced metabolic toxicity. Furthermore, it provides a theoretical basis for CA as a potential multi-target therapeutic agent and presents novel insights worthy of further investigation into the prevention of T2DM-NAFLD comorbidity. Full article

Type 2 diabetes (T2D) remains a major public health challenge in Africa, where limited healthcare access and the high cost of conventional therapies sustain reliance on African traditional medicine (ATM). This systematic review and meta-analysis evaluated the efficacy, mechanisms of action, and safety of African polyherbal formulations for T2D management. This systematic review and meta-analysis was conducted in accordance with PRISMA 2020 guidelines, following a protocol registered with PROSPERO (CRD420251168831). We searched PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar for studies published between 1 January 2011 and 31 December 2024. Seventeen studies met the inclusion criteria. Polyherbal formulations consistently improved glycaemic control, insulin sensitivity, antioxidant status, and lipid profiles. Meta-analysis of 10 preclinical studies demonstrated a significant reduction in fasting blood glucose compared with that of diabetic controls (SMD = −5.22, 95% CI: −5.55 to −4.89; p < 0.001; I² = 93.88%). Proposed mechanisms included β-cell protection, stimulation of insulin secretion, inhibition of α-amylase and α-glucosidase, and attenuation of oxidative stress. Safety data were limited and inconsistently reported. Human evidence was limited to one quasi-experimental clinical study and one acute human OGTT study. African polyherbal formulations demonstrate promising antidiabetic potential; however, methodological heterogeneity, limited phytochemical characterisation, inadequate safety assessment, and scarce clinical evidence highlight the need for standardised preclinical studies and well-designed clinical trials to support evidence-based integration into healthcare. Full article

This review examines the structural variety, distribution, and physicochemical properties of chlorogenic acids (CGAs), identifying coffee and green coffee as the leading dietary sources of these compounds. Preclinical studies indicate that plant-derived phenolic compounds exhibit strong antioxidant, anti-inflammatory, neuroprotective, cardioprotective, and antidiabetic effects across various disease models. The biological effectiveness of CGAs is attributed to their modulation of cellular signaling pathways, particularly by activating the erythroid 2-related factor 2 antioxidant defense mechanism and inhibiting the pro-inflammatory nuclear factor kappa B pathway. The regulation of the energy-sensing Sirtuin 1 and AMP-activated protein kinase pathways further enhances these therapeutic effects. In the gastrointestinal tract, CGAs serve as key modulators of the microbiota–gut–brain axis by exerting prebiotic-like effects, lowering the Firmicutes/Bacteroidetes ratio, promoting the production of short-chain fatty acids, and preserving gut barrier integrity. Some preclinical studies with coffee, Ilex paraguariensis, Eugenia uniflora, and other CGAs-rich extracts are also discussed. However, despite strong preclinical evidence, translating these findings into human clinical settings remains inconsistent due to significant individual differences in gut microbiota metabolism and the confounding effects of other components in dietary supplements, such as caffeine. Considering this, the review will first explore the molecular mechanisms supporting the potential development of CGAs as preventive interventions, while also discussing current human trials demonstrating selective improvements in neurological, cardiovascular, and metabolic functions. It will also highlight a historical limitation: the lack of studies on the bioavailability, bioactivity, and efficacy of isolated CGAs. The review will conclude by addressing the constraints of clinical studies, emphasizing the urgent need for future precision nutrition frameworks that employ standardized CGAs formulations to enhance potential therapeutic outcomes. Full article

Background: Combining natural products with conventional antidiabetic agents to inhibit α-glucosidase activity is an effective strategy for preventing postprandial hyperglycemia. Baicalein, a natural flavonoid with well-documented low toxicity, showed potential synergistic effect with acarbose in diabetic models; however, the synergistic performance and mechanisms of the two agents targeting human maltase–glucoamylase (MGAM) remain unclear. Methods: Recombinant human MGAM-C and MGAM-N were expressed in Pichia pastoris for in vitro inhibition assays. Maltose-loaded mice were used to assess the in vivo hypoglycemic activity and intestinal maltase inhibition. Inhibitor–enzyme interactions were investigated by fluorescence spectroscopy, circular dichroism (CD), multiple molecular docking, and molecular dynamics (MD) simulations. Results: Baicalein potently inhibited MGAM-C and MGAM-N with IC₅₀ values of 20.41 ± 4.80 μM and 14.04 ± 0.94 μM, respectively, and demonstrated a synergistic effect when combined with acarbose. In vivo, co-administration significantly reduced blood glucose levels and suppressed small intestinal maltase activity in maltose-loaded mice. Mechanistic studies revealed that baicalein functions as a non-competitive inhibitor by binding to the allosteric site of MGAM-C via stable hydrogen bonds with residues Ile1716 and Trp1749. This interaction induces conformational changes in the enzyme’s secondary structure and optimizes the hydrophobic microenvironment of the active site, thereby enhancing the binding affinity and hydrogen bond stability of acarbose. These molecular events collectively contribute to the synergistic inhibition of MGAM-C hydrolytic activity. Conclusions: This research revealed the synergistic inhibitory effect of baicalein and acarbose on MGAM and the underlying mechanisms, thereby providing a theoretical basis for developing pharmaceutical formulations to enhance acarbose efficacy. Full article

Metabolic syndrome (MetS) is a complex cluster of interconnected metabolic abnormalities, including central obesity, insulin resistance, dyslipidemia, hypertension, chronic inflammation, and impaired glucose metabolism, which collectively increase the risk of type 2 diabetes and cardiovascular diseases. Although current therapeutic strategies, including lifestyle interventions and pharmacological treatments, can be effective in managing specific MetS components, the multifactorial nature of this condition continues to encourage the search for complementary approaches and novel bioactive compounds. Salt-tolerant plants (STPs), particularly halophytes, survive under adverse saline and oxidative stress conditions through specialized physiological and biochemical adaptations, including the production of diverse secondary metabolites such as phenolic acids, flavonoids, sterols, terpenoids and polysaccharides. Several of these compounds have been associated with health-promoting properties, including antioxidant, anti-inflammatory, antidiabetic, antihypertensive, lipid-modulating and cardioprotective effects. This review provides an integrated and critical overview of the ethnomedicinal uses, phytochemistry and bioactivities of STPs with potential relevance to MetS and its associated conditions, namely chronic inflammation, diabetes, hypertension, cardiovascular disorders, dyslipidemia and obesity. The review first introduces the main features of MetS and the relevance of STPs as bioresources, followed by a synthesis of ethnomedicinal uses related to MetS-associated disorders. It then discusses in vitro and in vivo evidence for selected species, extracts and compounds, including reported bioactive metabolites and proposed mechanisms of action when available. Finally, the most promising species, extracts and metabolites are highlighted, together with current limitations and future research needs regarding efficacy, safety, bioavailability, standardization and clinical relevance. Full article

Accumulating data indicate a role for the dysregulation of the cell cycle, autophagy and apoptosis in diabetic kidney disease. We aimed to evaluate the mediators of the PI3K/Akt and MAPK/ERK signaling pathways in the kidney of db/db mice, a model of type 2 diabetes, treated by the SGLT2 inhibitor empagliflozin, the DPP4 inhibitor linagliptin, and metformin. Eight-week-old male db/db mice were randomly assigned to treatment by these agents or vehicle for 8 weeks. Age-matched db/+ mice acted as controls. AMPKα1 and PI3Kp110β were evaluated in the renal cortex and medulla by Western Blot. Phosphorylated forms of principal molecules involved in the PI3K/Akt and MAPK/ERK pathways were assessed by multiplex analysis. Db/db mice had decreased PI3Kp110β, increased phospho-PTEN, HSP27 and MEK1 in the renal cortex and medulla, BAD in the renal cortex and decreased phospho-rpS6 in the renal medulla. Empagliflozin prevented the changes in the levels of cortical PI3Kp110β, phospho-MEK1, and medullar phospho-PTEN. Linagliptin restored PI3Kp110β levels. Both agents further decreased medullar phospho-rpS6. Metformin upregulated cortical AMPKα1, medullar PI3Kp110β, phospho-GSK-3α/β and MEK1, and increased phospho-HSP27 in the renal cortex and medulla. The data may provide further explanation of the mechanism underlying the development of diabetic kidney disease, as well as the renal protective effect of anti-diabetic agents. Full article

Amomum tsaoko Crevost & Lem. (AT) is a representative edible, medicinal spice widely used in Southeast Asia for food seasoning and flavor enhancement. Growing evidence suggests that it is a rich source of bioactive phytochemicals with diverse health-promoting properties, necessitating a systematic synthesis of its functional attributes and underlying mechanisms to better guide future applications. AT has been reported to contain flavonoids, diarylheptanoids, phenolic acids, terpenoids, steroids, and volatile oils. These constituents are associated with a broad spectrum of biological activities, including antimicrobial, antidiabetic, antioxidant, anti-inflammatory, anticancer, neuroprotective, anti-obesity, gastrointestinal protective, and immunomodulatory effects. Due to its functional properties and economic value, AT shows considerable potential for application in functional foods, pharmaceuticals, cosmetics, and agriculture. However, despite its extensive utilization, integrated reviews that systematically link bioactivities, toxicological evidence, and industrial applications remain scarce. This review comprehensively summarizes recent advances in the bioactive compounds, health functions, toxicological evaluation, and industrial applications of AT. Current research progress, key limitations, and future perspectives are critically discussed. Additionally, by providing a comprehensive overview of its multifaceted benefits and applications, this review fills an important gap and offers insights to support further research and multi-sectoral exploitation of AT. Full article

Background: Bougainvillea species have been used in traditional Mexican medicine, but their bioactive compounds and mechanisms of action are insufficiently studied. This is the first comprehensive evaluation of fractions from the acetone extract of Bougainvillea × buttiana Holtum & Standl (var. Rose), combining phytochemical profiling with in vitro multitarget bioactivity assessment. Methods: Eleven fractions were analyzed for total phenolic (TPC) and flavonoid content (TFC) and antioxidant capacity using the DPPH assay. The most active fractions were further tested for nitric oxide (NO) scavenging, protection of erythrocytes and bovine serum albumin (BSA) from oxidative damage, inhibition of enzymes involved in inflammation (PLA₂, COX, LOX) and carbohydrate metabolism (α-glucosidase, α-amylase, tyrosinase), cytoprotective effects in L929 fibroblasts exposed to hydrogen peroxide, and their main metabolites were qualitatively identified by HPLC-UV-Vis. Results: All fractions showed significant TPC and TFC and concentration-dependent antioxidant activity. The fractions with the highest antioxidant indices were F5, F7, and F9. These effectively scavenged NO, protected erythrocytes and L929 cells (maintaining viability at 82.0%, 75.6%, and 72.0%, respectively), and inhibited key enzymes. Seven major compounds, mainly flavonoids, were identified. Conclusions: These findings showed that flavonoid-enriched fractions from B. × buttiana exhibit coordinated antioxidant, anti-inflammatory, antidiabetic, and cytoprotective effects, suggesting potential to treat oxidative stress-related disorders. Full article

Type 2 diabetes mellitus (T2DM) involves progressive muscle wasting, metabolic dysregulation in peripheral tissues, chronic hyperglycemia, and insulin resistance. Momordica charantia is an antidiabetic agent often limited by bitterness. To improve palatability and efficacy, we developed EMS by combining M. charantia and Stevia rebaudiana (9:1). EMS’s antidiabetic effects were tested in streptozotocin (STZ)-induced and genetic db/db mouse models of diabetes. Mice received oral EMS at doses (40, 80, and 120 mg/kg) for six weeks, assessing glucose tolerance, insulin sensitivity, lipid profile, and hepatic markers. Additionally, muscle protein synthesis and degradation mechanisms were analyzed in gastrocnemius tissues. EMS significantly reduced fasting blood glucose and improved insulin sensitivity in both models. EMS decreased liver lipid accumulation and serum ALT and AST levels, indicating hepatic protection. EMS alleviated muscle atrophy by increasing muscle fiber area and was associated with increased expression or activity of AMPK/Sirt1/PGC-1α and IRS-1/PI3K/AKT insulin pathways. It also suppressed FOXO3a-mediated expression of Atrogin-1 and MuRF1, suggesting reduced activation of protein-degradation pathways. Moreover, EMS modulated the gut microbiota, increasing the abundance of beneficial species such as Barnesiella intestinihominis. These findings suggest EMS is a promising multitarget functional ingredient for metabolic complications and musculoskeletal decline in T2DM. Full article