Search Results (3,068)

Background: Physical activity is a crucial component of diabetes prevention and management, yet participation varies across populations. Differences by country of birth may reflect cultural, socioeconomic, and structural factors that influence health behaviors among individuals with diabetic conditions. Objective: To examine the relationship between country of birth, diabetes status, and physical activity, and to assess whether country of birth is associated with diabetes prevalence. Methods: A cross-sectional analysis was conducted using U.S.-nationally representative data from the National Health and Nutrition Examination Survey (NHANES). Adults were categorized as having diabetes/prediabetes or no diabetes based on self-reported diagnosis. Physical activity was assessed using self-reported levels of moderate and vigorous leisure-time physical activity (LTPA). Sociodemographic characteristics were compared across groups. Stratified analyses were conducted to evaluate differences by country of birth and statistical tests were used to identify significant associations between diabetes status, physical activity, and sociodemographic variables. Results: Significant differences in sociodemographic characteristics were observed across diabetes status groups, particularly by age. There was no significant difference in physical activity levels between adults with diabetes compared to those without. Individuals with diabetes reported higher levels of sedentary time before adjustment for sociodemographic factors. Differences in physical activity behaviors were also observed in unadjusted analyses by country of birth, with foreign-born groups demonstrating lower levels of vigorous activity. Conclusions: Physical activity disparities exist among adults in the United States with diabetes and prediabetes and differ by country of birth, although they can be largely explained by sociodemographic factors. These findings highlight the need for culturally and socioeconomically tailored interventions to promote physical activity and support chronic disease management in diverse populations. Full article

Knee osteoarthritis (KOA) is a degenerative joint disease characterized by inflammatory reactions and bone lesions within the joint, which is mainly caused by the degeneration of articular cartilage. This disease primarily affects middle-aged and elderly populations, especially those over 50 years old; however, a distinct trend of younger onset has been observed in recent years, which is closely associated with factors such as sports-related injuries and obesity. Astaxanthin (AST), a ketone carotenoid belonging to the xanthophyll family, exhibits extremely strong antioxidant and broad-spectrum anti-inflammatory activities with no obvious toxic and side effects due to its unique molecular structure, thus showing great potential in the prevention and treatment of KOA. This article reviews the research evidence and action mechanisms of AST in the prevention and treatment of KOA from multiple aspects, including alleviating joint pain, reducing cartilage structural damage, resisting oxidative stress, inhibiting inflammatory responses, and regulating cartilage metabolism and functional disorders, while exploring the key factors and signaling pathways involved. On this basis, a strategy combining AST with exercise intervention for the prevention and treatment of KOA is proposed, which provides a certain reference for the clinical treatment and scientific research of KOA. Full article

Aortic dissection (AD) is a severe vascular condition marked by abrupt onset, rapid progression, and heightened mortality rates. Vascular smooth muscle cells (VSMCs), the predominant cellular component of the arterial media, are essential for maintaining the structural integrity and functionality of blood vessels. Recent studies have associated Cysteine-rich protein 2 (CSRP2) with the advancement of several vascular diseases. The involvement of CSRP2 in AD progression is unclear. Aortic tissues were collected from patients for RNA sequencing and histological analysis. A mouse model of AD was created using β-aminopropionitrile monofumarate (BAPN), while VSMC phenotypic switching was induced by platelet-derived growth factor BB (PDGF-BB). Adeno-associated virus vector was used to overexpress CSRP2 in aorta. A variety of histopathological assays and biochemical analyses were applied to determine gene and protein expression patterns as well as uncover underlying molecular mechanisms. CSRP2 was significantly downregulated in both human and murine AD, and CSRP2 gene overexpression dramatically reduced BAPN-induced AD incidence and prevented animal mortality. CSRP2 could preserve a contractile VSMC phenotype, even though under PDGF-BB stimulation. Mechanistically, our findings reveal that CSRP2 directly interacts with p130 Crk-associated substrate (p130Cas; also known as BCAR1) and reduces its phosphorylation, which in turn inhibits the activation of extracellular signal-regulated kinase (ERK) signaling pathways, thereby preventing VSMC phenotypic switching induced by PDGF-BB. Our findings identify CSRP2 as a novel regulator of VSMC phenotypic modulation and a significant modulator of AD development, suggesting its potential as a target for early intervention for AD. Full article

Staphylococcus aureus (S. aureus), a leading cause of nosocomial infections, contributes significantly to increased morbidity and mortality, especially when it forms biofilms on medical devices. This pathogen, specifically methicillin-resistant S. aureus (MRSA), remains a challenge to treat due to its ability to form biofilms and rapidly develop resistance against antibiotics. Biofilm formation allows bacteria to adhere to biotic and abiotic surfaces, creating a protective matrix that shields them from immune responses and antibiotic therapies. The widespread prevalence of multidrug-resistant S. aureus biofilms poses a significant therapeutic challenge in clinical settings. Several novel therapeutic strategies have been developed to combat S. aureus biofilm-associated infections. Accumulating evidence suggests that natural plants and their derivatives possess antimicrobial and chemo preventive properties that can disrupt established biofilms. Several plant-derived compounds with anti-biofilm activities have been reported to target the regulatory proteins involved in the Agr quorum sensing (Agr-QS) system, underscoring their potential as therapeutic candidates for the prevention and treatment of biofilm-associated infections. However, despite these encouraging findings, clinical validation of these plant-based agents is essential to ensure their efficacy, safety, and optimal application in treating S. aureus biofilm infections. The continued exploration of natural biofilm inhibitors anticipates the urgent need for new treatments to combat biofilm-associated infections and multidrug-resistant pathogens like MRSA. This review provides a detailed overview of preventive and therapeutic interventions to eradicate biofilm-forming S. aureus infections. Full article

Background: Calcium formulations are important nutritional interventions for improving insufficient calcium intake and assisting in the prevention and treatment of osteoporosis. In vitro and in vivo performance may be influenced by dosage form, calcium source, and formulation composition. In this study, an integrated approach combining in vitro dissolution, pharmacokinetic, and pharmacodynamic evaluations was used to compare the comprehensive performance of nine calcium formulations and related functional components. Methods: The nine samples were coded as CS-1 to CS-9 according to a predefined order. Calcium release characteristics were determined under simulated gastrointestinal pH conditions using a flow-through cell system. Calcium concentrations in rat plasma, feces, and urine were measured by inductively coupled plasma optical emission spectrometry (ICP-OES) to evaluate calcium exposure, excretion, and retention. Meanwhile, the bone-protective effects of different calcium preparations were assessed in a retinoic acid-induced osteoporotic ICR mouse model, and the pharmacodynamic performance of calcium citrate and various bone-derived peptide preparations was investigated in a calcium-deficient female Sprague–Dawley (SD) rat model. Results: CS-1 exhibited rapid and nearly complete calcium release in simulated gastric fluid and showed a relatively favorable dissolution profile under sequential gastrointestinal pH conditions. Calcium balance analysis indicated that calcium retention in rats was relatively higher after administration of CS-1. Animal experiments showed that different calcium sources and bone-derived peptide preparations improved bone-related parameters to varying degrees, among which CS-1 produced relatively consistent improvements in bone microarchitecture and biomechanical properties. As a functional component of the CS-1 formulation, salmon bone-derived ingredients showed activity in the comparative pharmacodynamic evaluation, suggesting that they may contribute to the overall bone-protective effect. Conclusions: Different calcium formulations showed distinct profiles in dissolution behavior, calcium retention, and bone-protective effects. Among the tested samples, CS-1 demonstrated relatively favorable overall performance, which may be related to its liquid dosage form and salmon bone-derived functional components. Full article

The oral microbiota represents a complex and dynamic microbial ecosystem that plays a critical role in preserving both oral and systemic homeostasis. Emerging evidence suggests that alterations in oral microbial milieu (dysbiosis) may contribute to the pathogenesis of neurodegenerative disorders, especially Alzheimer’s disease (AD), through the oral–brain axis. This review synthesizes current evidence on the pathways linking oral microbiota to cognitive decline, integrating microbial, immunological, and vascular perspectives. Oral pathogens may access the central nervous system via hematogenous dissemination or neural routes, including the trigeminal nerve, while simultaneously promoting systemic inflammation, immune activation, and blood–brain barrier disruption. These processes converge on key neurodegenerative mechanisms, including chronic neuroinflammation, amyloid-β accumulation, and tau pathology. In parallel, alterations in oral microbial composition have been linked to disease severity, supporting a potential role of dysbiosis in both initiation and progression of cognitive impairment. Diet emerges as a critical modifiable determinant of oral microbial ecology. Diets rich in refined sugars may promote dysbiosis and inflammatory signaling, whereas (poly)phenols, probiotics, and prebiotics may support microbial eubiosis and exert neuroprotective effects through modulation of host–microbe interactions. Although current evidence remains largely observational and mechanistic, the diet–oral microbiota–brain axis represents a promising target for preventive and therapeutic strategies aimed at mitigating cognitive decline and promoting healthy aging. Future longitudinal and interventional studies are required to establish causality and translate these insights into clinical practice. Full article

In low- and middle-income countries, the burden of hypertension and hyperglycaemia is alarming. These conditions remain major, recurring public health concerns that demand alternative healthcare strategies. This systematic review critiques and synthesises the existing evidence on the roles of recreational activities and dietary management in treating hypertension and hyperglycaemia in adults in low- and middle-income countries. The aim is to create awareness for hypertensive and hyperglycaemic patients. A systematic search was conducted using the PRISMA guidelines across six online databases: PubMed, Scopus, Google Scholar, Cochrane Library, Web of Science, and CINAHL. The search included peer-reviewed articles published between 2015 and 2025. Of the 12,500 identified articles, only 35 met the inclusion criteria. The evidence suggests that active recreational activities and dietary interventions are the most effective strategies for managing hypertension and hyperglycaemia when implemented properly. Current studies demonstrate that aerobic recreational activity improves vascular function, lowers blood pressure, and enhances insulin sensitivity. DASH and Mediterranean diets support cardiometabolic health in hypertensive and hyperglycaemic patients. These diets help reduce hypertension, control blood sugar levels, and lower cardiovascular risk. If sustained, these intervention strategies can effectively prevent and manage hypertension and hyperglycaemia. This review recommends that healthcare systems integrate therapeutic recreational activities with the DASH and Mediterranean diets as alternative interventions for adults with hypertension and hyperglycaemia. Full article

Background: Global aging has led to a rise in neurodegenerative diseases. Neuroinflammation constitutes a core pathological mechanism in these disorders. The Kongsheng Zhenzhong Pill (KSZZP), a modern preparation derived from a classical Chinese herbal formula, are reputed for their sedative and cognition-enhancing effects. However, the molecular mechanism underlying its modulation of microglia-mediated neuroinflammation remains unclear. The present study was designed to assess the intervention effects of KSZZP on LPS-induced neuroinflammation in BV-2 microglial cells and to preliminarily explore the potential molecular mechanisms involved. Methods: An in vitro neuroinflammation model was established in LPS-induced BV-2 microglial cells. The chemical components of KSZZP were identified using UPLC-Q-Exactive HFX technology. The pharmacological effects of KSZZP were evaluated by assessing cell activation, inflammatory response, oxidative stress, and apoptosis. Molecular docking and Western blotting were used to explore the specific mechanism of its action on the cGAS-STING pathway. Results: Chemical analysis identified 67 components in KSZZP, primarily flavonoids, prenyl lipids, and isoflavones. KSZZP treatment dose-dependently inhibited LPS-induced BV-2 microglial activation and significantly reduced pro-inflammatory factor release. Furthermore, it alleviated oxidative stress, mitigated mitochondrial ultrastructural damage, and inhibited apoptosis induced by LPS. Molecular docking revealed that key active components of KSZZP exhibit strong binding potential to cGAS and STING proteins. Western blotting further confirmed that KSZZP dose-dependently suppressed the expression of key cGAS-STING pathway proteins (cGAS, STING) and downstream proteins associated with M1 polarization (iNOS, TNF-α, COX-2). Conclusions: This study indicates that KSZZP alleviates LPS-induced microglial activation, neuroinflammation, oxidative stress, mitochondrial damage, and apoptosis, and these effects may involve the modulation of the cGAS-STING signaling pathway. Collectively, these findings provide a preliminary experimental basis for understanding the anti-neuroinflammatory mechanism of KSZZP and support its potential application in the prevention and treatment of neurodegenerative diseases. Full article

Background/Objectives: Extra virgin olive oil (EVOO), a key component of the Mediterranean diet, has attracted research interest because olive-derived phenolics demonstrate potential anticancer activity in experimental models. This review summarizes evidence concerning whole EVOO, phenolic-enriched EVOO, olive phenolic extracts, and the isolated compounds hydroxytyrosol, oleuropein, oleocanthal, and oleacein. Methods: A structured narrative search of PubMed, Web of Science, ScienceDirect, and Google Scholar was conducted for literature published between 2015 and 2025. Evidence was reviewed for breast, prostate, colorectal, pancreatic, bone, oral, liver, gastric, hematological, and brain cancers. Comparatively limited evidence concerning cervical, endometrial, ovarian, melanoma, non-melanoma skin, and thyroid cancers was summarized separately. Results: The molecular evidence was derived primarily from cell culture and animal studies using isolated phenolics and concentrated extracts. Preclinical studies indicate that EVOO phenolics may demonstrate anticancer activity through multiple mechanisms, including antioxidant activity, anti-inflammatory effects, cell cycle arrest, induction of apoptosis, inhibition of metastasis, anti-angiogenic activity, and modulation of key signaling pathways, such as PI3K/AKT/mTOR, MAPK/ERK, NF-κB, JAK/STAT, Wnt/β-catenin, p53, and epithelial–mesenchymal transition-related pathways. Most molecular and pathway-level evidence was obtained using isolated phenolic compounds in cell culture or animal models, whereas evidence directly examining whole EVOO consumption was largely observational and substantially more limited. Experimental studies also reported that oleocanthal induced lysosomal membrane permeabilization, whereas hydroxytyrosol and oleuropein promoted mitochondria-mediated apoptosis. Furthermore, preclinical combination studies suggested enhanced tumor-cell sensitivity to selected chemotherapeutic, targeted, and immunotherapeutic agents. However, these effects have not been established in patients. Human evidence remains limited mainly to observational dietary associations and small exploratory interventions, with no conclusive demonstration of cancer prevention or therapeutic efficacy. Conclusions: Isolated EVOO-derived phenolic compounds demonstrated promising anticancer mechanisms in preclinical models. However, these results should not be directly extrapolated to dietary EVOO because experimentally administered doses, bioavailability, metabolism, and food-matrix interactions differ substantially from human dietary exposure. Therefore, well-designed studies using chemically characterized EVOO, pharmacokinetic investigations, and controlled human trials are required before dietary or clinical recommendations can be made. Full article

Obesity is a global metabolic disease closely associated with dyslipidemia, insulin resistance, hepatic steatosis, and chronic oxidative stress. Cydonia oblonga Miller (COM, Quince) from Xinjiang Uygur Autonomous Region of China is a traditional medicinal and edible plant rich in polyphenols, flavonoids, polysaccharides, and other bioactive constituents. Our previous studies suggested that total polyphenols of Cydonia oblonga Miller (TPCOM) may exert promising anti-obesity effects. Objective: This study aimed to investigate the therapeutic effects of TPCOM on high-fat diet-induced obese C57BL/6 mice and to explore its underlying molecular mechanisms related to glycolipid metabolism. Methods: TPCOM was extracted and purified from Xinjiang Cydonia oblonga fruits, and its total polyphenol content was determined using the Folin–Ciocalteu method. C57 mice were randomly divided into normal diet, model, and TPCOM intervention groups. After 12 weeks of high-fat diet feeding and 6 weeks of TPCOM treatment, body weight was monitored continuously. Serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and total antioxidant capacity (T-AOC) were measured using commercial kits. Hepatic pathological changes were observed by hematoxylin–eosin (HE) staining. Bioinformatics analyses including GO and KEGG were performed to predict key targets and pathways related to lipid metabolism. The protein expression levels of PPARGC1A, FFAR1, KLF15, Adipolin, GLUT4, and phosphorylated p38 MAPK in liver tissues were detected by Western blotting. Results: TPCOM intervention significantly reduced body weight gain in obese mice in a dose-dependent manner. Serum biochemical assays showed that TPCOM decreased TC, TG, and LDL-C levels, increased HDL-C levels, and markedly enhanced total antioxidant capacity (T-AOC). Bioinformatics analysis suggested that PPARG and FFAR1 were highly expressed in liver tissue and may participate in glucose and lipid metabolism regulation. Western blot results confirmed that TPCOM significantly upregulated the expression of PPARGC1A, FFAR1, KLF15, Adipolin, GLUT4, and phosphorylated p38 MAPK in the liver of obese mice. Conclusions: TPCOM effectively ameliorates obesity, dyslipidemia, hepatic steatosis, and oxidative stress in high-fat diet-induced obese mice. The underlying mechanism may be related to the regulation of glycolipid metabolism, mitochondrial function, insulin sensitivity, and antioxidant signaling via activating the FFAR1–PPARG–p38 MAPK axis and downstream targets including PPARGC1A, KLF15, Adipolin, and GLUT4. This study provides a scientific basis and theoretical support for the development and application of TPCOM as a natural functional ingredient in the prevention and adjuvant treatment of obesity and related metabolic disorders. Full article

Urologic malignancies (UMs), including prostate cancer (PCa), bladder cancer (BCa), renal cell carcinoma (RCC), and testicular germ cell tumors (TGCT), are governed by interconnected molecular pathways that regulate proliferation, angiogenesis, metabolism, invasion, immune escape, and treatment resistance. Key pathways include PI3K/AKT/mTOR, VEGF/VEGFR, EGFR, FGFR, c-MET, androgen receptor signaling, DNA damage response, inflammatory transcriptional programs, and regulation of the tumor microenvironment. This structured expert review evaluates mechanistic, translational, epidemiological, and clinical evidence on food- and botanical-derived nutraceuticals that may influence cancer-related signaling, redox balance, inflammation, metabolic adaptation, and host–tumor interactions. Nutraceuticals are considered investigational adjunctive exposures rather than anticancer treatments or alternatives to standard care. Relevant literature was identified through a structured, non-systematic search of PubMed/MEDLINE, Scopus, Web of Science Core Collection, and Embase from database inception to 17 June 2026, supplemented by backward and forward citation searches. Eligible evidence comprised preclinical, observational, interventional, pharmacokinetic, formulation, safety, and drug–nutraceutical interaction studies. Evidence was evaluated by cancer type, compound class, molecular context, formulation, exposure, translational maturity, and safety, and was classified into five stages: prevention signal, mechanistic plausibility, bioavailability and exposure feasibility, exposure-linked biomarker activity, and clinical benefit. An exposure–species–compartment framework was used to assess whether parent compounds and relevant metabolites reached systemic, urinary, or target-tissue concentrations compatible with the proposed effects. Findings based solely on supraphysiological concentrations of unconjugated parent compounds were considered hypothesis-generating unless supported by human exposure or tissue-distribution data. Curcumin, green tea catechins, isoflavones, carotenoids, flavonols, stilbenes, and triterpenoids affect several cancer-related pathways, primarily in experimental models. Translation to clinical practice is constrained by inconsistent formulations, limited bioavailability, inadequate target-tissue exposure data, few biomarker-linked studies, and possible interactions with anticancer therapies. PCa and BCa provide the most suitable settings for exposure-verified mechanistic studies. In RCC, safety and treatment interactions should be prioritized, whereas in TGCTs, non-interference with curative cisplatin-based therapy must be demonstrated. Future studies should use chemically defined formulations, verify clinically relevant exposure, incorporate mechanism-matched biological-response endpoints, and confirm compatibility with established treatment. Current evidence does not support nutraceuticals as treatments for urologic malignancies. Full article

Metabolic syndrome (MetS) is a complex and heterogeneous condition characterized by the coexistence of obesity, type 2 diabetes mellitus (T2DM), hypertension, chronic low-grade inflammation, and metabolic dysfunction. Increasing evidence suggests that the gut microbiota plays a central role in the development and progression of MetS by influencing host metabolism, intestinal barrier integrity, immune activation, endocrine signaling, and vascular homeostasis. This narrative review summarizes current evidence regarding gut microbiota alterations across major obesity-related metabolic phenotypes, including obesity alone, obesity complicated by T2DM, and obesity associated with hypertension. Obesity is generally characterized by reduced microbial diversity, depletion of beneficial taxa such as Faecalibacteriumprausnitzii and Akkermansia muciniphila, impaired short-chain fatty acid (SCFA) signaling, increased intestinal permeability, and metabolic endotoxemia. The coexistence of T2DM is associated with a more pronounced depletion of butyrate-producing bacteria, altered bile acid metabolism, impaired incretin signaling, and enhanced inflammatory activation that may contribute to insulin resistance and hyperglycemia. In hypertensive obesity, gut dysbiosis appears to preferentially involve disturbances within the gut–vascular axis, including reduced SCFA-producing taxa, increased trimethylamine N-oxide production, endothelial dysfunction, oxidative stress, and vascular inflammation. Although microbial signatures partially overlap among metabolic phenotypes, functional alterations in microbial metabolites and host–microbiota interactions may better explain disease heterogeneity than isolated taxonomic changes. Current evidence supports the potential role of microbiota-targeted interventions and integrated multi-omics approaches in future precision medicine strategies for cardiometabolic disease prevention and management. Full article

Primary prevention is essential to reduce disease burden before clinical onset, yet it remains less systematically integrated into care than diagnosis and treatment. Although artificial intelligence (AI) is increasingly used in medicine, most applications have focused on secondary and tertiary prevention, including diagnosis, prognostic stratification, and disease management, while its role in primary prevention remains less defined. This narrative review examines current AI applications across four modifiable lifestyle domains relevant to prevention and healthspan promotion: nutrition, physical activity, sleep, and mental health. We synthesize evidence on machine-learning models, wearable-derived algorithms, computer-vision tools, just-in-time adaptive interventions, and conversational agents used in consumer, community, and hybrid clinical–digital settings. AI applications support postprandial glycemic prediction, automated dietary assessment, meal-planning adherence, sedentary-pattern detection, personalized exercise recommendations, adaptive behavioral nudges, sleep monitoring, circadian-aware recommendations, psychoeducation, stress-management support, and early identification of psychological vulnerability. Collectively, these tools may extend prevention beyond episodic clinical encounters toward continuous, personalized, and context-aware support. However, evidence remains limited by short follow-up, reliance on surrogate or engagement outcomes, digitally literate populations, and insufficient validation in real-world preventive-care pathways. AI is therefore a promising enabling technology for proactive, healthspan-oriented medicine, provided future studies demonstrate long-term effectiveness, equity, safety, and responsible implementation. Full article

Background/Objectives: School-based programmes may play an important role in promoting healthier and more sustainable dietary habits from early childhood. This study described and evaluated a community-based intervention aimed at promoting Mediterranean diet (MD) principles, improving food literacy, and raising awareness of sustainable food practices among primary school children in the Tagus Lezíria region, Portugal. Methods: The intervention was implemented in 23 schools across 11 municipalities and included two seasonal rounds of participatory educational activities focused on healthy eating, local and seasonal foods, sensory exploration, balanced meals, composting, food storage, sustainable food production, and food waste prevention. A total of 872 children participated in the intervention activities, and 370 provided paired baseline and follow-up KIDMED assessments. Results: The mean KIDMED score decreased significantly from 8.0 ± 2.2 at baseline to 7.5 ± 2.4 after the intervention. Overall, 31.6% of participants improved their score, 18.9% showed no change, and 49.5% showed a decrease. The proportion of children who did not skip breakfast increased from 79.8% to 88.6%, and avoidance of fast-food restaurants more than once weekly increased from 85.4% to 89.6%. Smaller favourable changes were observed for pastry, sweet, and fish consumption, and olive oil use, whereas fruit, vegetable, pulse, and nut consumption did not improve. Conclusions: The intervention produced heterogeneous outcomes. Although overall MD adherence decreased, almost one-third of participants improved individually, with favourable changes in breakfast and selection of less healthy behaviours. Longer programmes with stronger family involvement may be required to reinforce core MD foods and achieve broader, sustained improvements. Full article

Chickpea is an important source of plant flavonoids in the diet, and flavonoids from chickpea have hypoglycemic activity. In this study, a male SD rat model of type 2 diabetes mellitus (T2DM) induced by a high-fat high-sugar diet combined with streptozotocin (STZ) was used to investigate the inhibitory effects on the polyol pathway (a branch of glucose metabolism) by chickpea flavonoid extract (CFE). The results demonstrated that CFE significantly lowered fasting blood glucose (FBG) level, and reduced insulin resistance in diabetic rats by elevating the homeostasis model assessment of insulin sensitivity (HOMA-IS) and decreasing the homeostasis model assessment of insulin resistance (HOMA-IR). And CFE relieved oxidative stress through reducing H₂O_2, malondialdehyde (MDA) and carbonylated protein levels, and increasing the activity of glutathione peroxidase (GSH-Px). Moreover, CFE inhibited the polyol pathway by downregulating the aldose reductase (AR) and sorbitol dehydrogenase (SDH) activities, as well as reducing the sorbitol and fructose levels. Meanwhile, CFE also enhanced the antioxidant defense capacity through increasing glutathione reductase (GR) activity and the glutathione (GSH) level, while decreasing the oxidized glutathione (GSSG) level. Further results showed that CFE mitigated reductive stress in T2DM rats via increasing intracellular NAD⁺ content and the NAD⁺/NADH ratio, due to suppressing PARP activity and upregulating Sirt3 activity. Furthermore, CFE regulated the levels of metabolites such as nicotinamide and β-aminobutyric acid, and modulated seven metabolic pathways closely associated with the improvement of diabetes and its complications. Ten key differential metabolites were reversed after CFE intervention, which were strongly correlated with the polyol pathway and oxidative stress in T2DM rats. In summary, CFE possessed hypoglycemic activity and could inhibit the polyol pathway, which was considered a promising natural product for diabetes prevention. Full article