Search Results (300)

Influenced by various physical, chemical, and microbial factors, the aging process of Citri Reticulatae ‘Chachiensis’ Pericarpium (CRCP) poses a complex scientific challenge. Drawing inspiration from the perspective of traditional Chinese medicine, volatile oils were extracted from CRCP aged 1, 3, 5, and 7 years by steam distillation and subsequently analyzed by GC-MS. The results revealed that the relative percentage of 4-vinylguaiacol (4-VG) increased progressively with aging. Nineteen volatile oil components were further assessed for their glucose metabolism-enhancing activities, with 4-VG emerging as a key active compound. Notably, 4-VG remarkably enhanced insulin-stimulated glucose uptake in C2C12 myotubes. Moreover, 4-VG demonstrated potent antihyperglycemic effects by upregulating IRS-1/Akt/GSK-3β phosphorylation in the insulin signaling pathway on a high-fat diet and STZ-induced diabetic mouse model. In addition, the metabolic pathway of 4-VG, from ferulic acid and then to vanillin and guaiacol, was verified via HPLC-UV, metabolomics, and microbiome analyses, which confirmed the microbial conversion of 4-VG within CRCP. The metabolic pathway was ultimately validated by isolating and identifying Priestia aryabhattai, Bacillus velezensis, and Aspergillus fumigatus from CRCP, with further in vitro culture and biotransformation experiments confirming its functionality and efficiency. These findings provide new insights and experimental evidence that deepen our understanding of the aging process of CRCP. Full article

Metformin, an oral antihyperglycemic drug, represents the cornerstone of pharmacological treatment for type 2 diabetes mellitus (T2DM). Its primary glucose-lowering effects are well established, predominantly mediated through the activation of AMP-activated protein kinase (AMPK). This activation leads to a reduction in hepatic glucose production (primarily by inhibiting gluconeogenesis and glycogenolysis) and an increase in peripheral glucose uptake and utilization. Beyond its direct impact on glucose metabolism, metformin also improves insulin sensitivity and has beneficial effects on lipid profiles. Increasingly, research shows that metformin has pleiotropic effects. In addition to its recognized antihyperglycemic action, metformin is emerging as a regulator of cellular processes implicated in aging. Indeed, emerging evidence suggests a potential role of metformin in modulating pathways associated with longevity and ameliorating the symptoms of age-related diseases, including neurodegenerative disorders (such as Alzheimer’s and Parkinson’s diseases), cardiovascular diseases, age-related macular degeneration, and osteoporosis. The proposed mechanisms for these broader effects involve AMPK activation, modulation of the mTOR pathway, reduction of oxidative stress, and promotion of autophagy. After exploring the established role of metformin in T2D, this review provides a comprehensive investigation of its promising applications in the context of age-related diseases, offering valuable insights into its multifaceted therapeutic potential beyond glycemic control. Full article

Diabetic nephropathy (DN) is a consequence of diabetes mellitus (DM), in which hyperglycemia triggers osmotic and oxidative stress and activates inflammatory pathways. These processes damage kidney cells, with mesangial cells (MCs) undergoing mesangial expansion. Antihyperglycemic drugs prevent the progression of renal disease. Although tamsulosin is not conventionally used for the treatment of DN, its previously reported anti-fibrotic and anti-inflammatory effects in liver and lung injury models suggest that it may exert renoprotective actions like those of pioglitazone, which has also been shown to improve cellular carbohydrate and lipid metabolism. MCs were exposed to 20 mM glucose medium and treated with either 50 nM tamsulosin or 100 nM pioglitazone. Subsequently, cell proliferation, inflammatory markers (NF-κB, IL-1β, IL-17), fibrogenic markers (TGF-β, collagen I), oxidative stress parameters (NRF2, superoxide), and indicators of mesangial activation (α-SMA, rhodamine–phalloidin) were assessed in vitro. Both treatments reduced cellular proliferation and hypertrophy, attenuated the release of reactive oxygen species (ROS), decreased IL-17 and α-SMA expression, and reduced mesangial activation and hypertrophy. In an in vivo model of DN in Wistar rats, both treatments decreased mesangial cell activation and expansion. In conclusion, tamsulosin and pioglitazone exert anti-fibrogenic and anti-inflammatory effects in MCs exposed to HG, thereby limiting mesangial activation and expansion. Full article

Sesame oil extraction byproduct (SOEB) contains a high percentage of protein (49.81 g/100 g), making it a suitable plant-based source for producing protein hydrolysates with nutraceutical potential. In this study, albumins, globulins, glutelins, and prolamins fractions were extracted and characterized from SOEB. These fractions were then enzymatically hydrolyzed with alcalase, yielding high soluble protein content (>90%) and hydrolysis degrees ranging from 34.66 to 45.10%. The hydrolysates were fractionated by molecular weight (<5 kDa, 3–5 kDa, 1–3 kDa, and <1 kDa). These fractions demonstrated potential for inhibiting the DPPH radical (25.19–95.79%) and the α-glucosidase enzyme (40.14–55.63%), particularly the fractions with molecular weight <1 kDa. We identified 28 peptides, with molecular weights between 332.20 and 1096.63 Da, which showed potent antioxidant activities (IC₅₀ = 90.18 µg/mL), as well as inhibitory effects on key enzymes such as α-glucosidase (IC₅₀ = 61.48 µg/mL), dipeptidyl peptidase IV (IC₅₀ = 12.12 µg/mL), and pancreatic lipase (IC₅₀ = 6.14 mg/mL). These results demonstrate the antioxidant, antihyperglycemic, antidiabetic, and anti-obesity potential of SOEB peptides, highlighting their use in the formulation of new functional foods or nutraceuticals. Full article

Micromeria graeca (L.) Benth. ex Rchb. (Lamiaceae) is a promising medicinal plant valued for its antioxidant, anti-hyperglycemic, anti-hypertensive, antimicrobial, and anti-aflatoxigenic properties. It is rich in phenolic and flavonoid compounds, supporting its traditional use for digestive, respiratory, cardiovascular, and dermatological conditions. Plant tissue culture facilitates controlled in vitro propagation to study plant growth and bioactive properties. The effects of activated charcoal and varying subculture intervals on multiplication and biomass production in M. graeca shoot cultures were investigated. The phenolic composition of methanolic extracts from in vitro-grown plants was characterized using high-performance liquid chromatography (HPLC), identifying rosmarinic, caffeic, and syringic acids as the primary phenolic compounds. Antimicrobial activity against selected microbial strains was evaluated using a micro-well dilution assay. Anticancer activity of selected extracts was assessed in human hepatocellular carcinoma cell line HepG2, with flow cytometry (Annexin-V/PI staining) used to analyze cell death mechanisms, and compared to pure rosmarinic acid (RA). Activated charcoal showed no beneficial effects on multiplication or biomass production, but significantly increased phenolic acid content (up to 4-fold). RA dominated the phenolic profiles, with other phenolic acids present in lower amounts. Methanolic extracts exhibited negligible antimicrobial activity compared to reference antibiotics and fungicide. Extracts from 4-week-old shoot cultures displayed modest anti-hepatoma activity (IC50 values of CV assay ranging from 193 to 274 µg mL⁻¹), inducing HepG2 cell apoptosis via oxidative stress, independent of RA. Our results suggest that the metabolic output of M. graeca shoot cultures and consequently their biological activity can be modulated by varying in vitro culture conditions. These findings underscore the potential of their methanolic extracts for biotechnological production and therapeutic applications. Full article

Type 2 diabetes is a multifactorial disease characterized by chronic hyperglycemia, insulin resistance, oxidative stress, inflammation, and dyslipidemia, factors that contribute to the development of long-term complications. In this context, the 2-aminobenzothiazole scaffold has emerged as a promising candidate due to its broad spectrum of biological properties. In this study, we performed a multidisciplinary evaluation of benzothiazole derivatives (5a–d, 8a–d, 11a–d, and 12c–d), starting with the in silico prediction of their properties, along with molecular docking against aldose reductase (ALR2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). All compounds complied with the main rules of pharmacological similarity and optimal affinity, highlighting 8d (ΔG = −8.39 kcal/mol for ALR2 and −7.77 kcal/mol for PPAR-γ). Selected compounds from families C and D were synthesized in moderate yields (~60%) and showed low acute oral toxicity (LD₅₀ > 1250 mg/Kg). Compounds 8c and 8d inhibited ALR2 at concentrations below 10 µM. In vivo studies using a streptozotocin-induced diabetic rat model with a high-fat diet revealed that compound 8d produced sustained antihyperglycemic effects and reduced insulin resistance, dyslipidemia, and polydipsia, without inducing hepatotoxicity or displaying intrinsic antioxidant or anti-inflammatory activity. These findings suggest that 8d is a promising candidate for further development in diabetes-related therapeutic strategies. Full article

There is increasing use of modern medicine globally to manage cardiovascular diseases (CVDs). However, many people, especially in low-to-middle-income countries, still rely on traditional medicinal plants for their daily health needs. However, limited studies have explored the use of these remedies. Therefore, this narrative review aimed to evaluate the potential of Sclerocarya birrea (S. birrea) in managing diabetes, dyslipidemia, inflammation, and hypertension, including its effects on oxidative stress. This study reviewed evidence from PubMed, Web of Science, and ResearchGate, published in these databases up to 30 April 2025. The evidence showed that S. birrea had the potential to preserve cardiometabolic health and reduce CVD-associated risk factors. Notably, S. birrea improved glucose metabolism, inflammation, hypertension, and oxidative stress. This plant exhibits antihyperglycemic effects by activating adenosine monophosphate-activated protein kinase (AMPK) and inhibiting gluconeogenesis and the activities of carbohydrase. It also ameliorates dyslipidemia by modulating the activities of peroxisome proliferator-activated receptor alpha (PPARα) and increasing fatty acid oxidation. The anti-inflammatory potential of S. birrea is modulated by the activation of PPARα, which inhibits nuclear factor kappa beta (NF-κβ) and decreases the production of inflammatory cytokines. Its antioxidant property is attributed to its ability to increase antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), which are known to counteract oxidative damage. However, it is important to note that different parts of the plant had varying impacts on CVD risk factors, depending on whether the study was conducted preclinically or clinically. Therefore, its extract should be explored as a potential remedy for the management of CVD risk factors, especially in areas where access to healthcare is limited. Full article

Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM. Full article

Deoxynojirimycin (DNJ), the first isolated iminosugar, is a natural alkaloid acting as a potent inhibitor of α-glucosidase with high nutritional value. It naturally occurs in plants (especially Morus spp.), microbes, and insects or can be synthesized. Diverse biological activities, such as antihyperglycemic, lipid-lowering, antitumor, antiviral, and anti-inflammatory, have been recognized for this compound. However, DNJ has not been approved as a food supplement until now. Several studies, also in clinics, are carried out on Morus spp. containing DNJ. Among Morus spp., Morus alba L. (white mulberry), Morus nigra L. (black mulberry), and Morus rubra L. (red mulberry) are the three main species that grow all over the world. Some spurious studies have been conducted on Reducose^® and Glubloc™, two products that contain DNJ and Morus alba, respectively. However, mulberry allergy, including respiratory allergy, airborne contact urticaria, anaphylaxis, oral allergy syndrome, and food induced urticaria, may be observed. This review aims to explore a crucial and timely question: how DNJ exerts its biological effects and what role it may play in therapeutic applications. We provide a comprehensive summary of the current understanding of DNJ’s pharmacological potential and the methods used for its production. We also report recent developments in clinical studies on Morus alba, Reducose^® and Glubloc™. Full article

Rosemary (Salvia rosmarinus) is renowned for its antioxidant, anti-inflammatory, and antihyperglycemic properties, largely attributed to its rich phytochemical profile. This study evaluates the potential of metabolites from Pseudomonas shirazensis NFV3, formulated in silver nanoparticles (AgNPs), to enhance the bioactivity of rosemary extracts in postharvest applications. Rosemary stems were treated with AgNPs coated with bacterial metabolites (NP), bacterial cells, or metabolites (LM), and the extracts’ phytochemical composition and bioactivities were assessed. HPLC and HPLC–MS analyses revealed that the NP treatment induced significant metabolic remodeling, particularly upregulating rosmarinic acid and selected triterpenes (ursolic and betulinic acids), while reducing carnosic acid levels. NP-treated extracts exhibited significantly enhanced inhibition of cyclooxygenase (COX-1 and COX-2), indicating improved anti-inflammatory potential. The α-glucosidase inhibition and antioxidant activity (DPPH assay) of the extracts were not substantially altered, suggesting the selective enhancement of pharmacological functions. These findings demonstrate that nanoparticle-based elicitation selectively remodels secondary metabolism in rosemary, improving extract quality and bioactivity. This strategy offers a novel, sustainable tool for optimizing plant-based therapeutics in the phytopharmaceutical industry. Full article

Mauritia flexuosa, commonly known as “canangucha,” holds significant nutritional and economic value in the Amazon region. While its pulp is widely utilized in local food products, the seed or kernel is largely underutilized. This study investigated the proximal and phytochemical composition of M. flexuosa, alongside its biological properties, specifically focusing on the hypoglycemic activity of an ethanolic extract from M. flexuosa seeds (MFSs). Proximal analysis revealed that MFSs are a notable source of crude fiber (28.4%) and a moderate source of protein (9.1%). Phytochemical screening indicated a high total polyphenol content (123.4 mg gallic acid equivalents/100 mg dry weight) and substantial antiradical capacity against the ABTS radical (IC₅₀ = 171.86 µg/mL). Notably, MFS ethanolic extracts exhibited significant in vitro antihyperglycemic activity via inhibiting α-amylase and α-glucosidase enzymes, demonstrating comparable inhibition to acarbose at higher concentrations. This hypoglycemic effect was further corroborated in an in vivo rat model with induced diabetes, where the administration of 100 mg/kg of MFS ethanolic extract significantly reduced blood glucose levels compared to the diabetic control group (p < 0.05). A moderate antihypertensive effect was observed at a concentration of 150 mg/kg, correlating with ACE inhibition. High-performance liquid chromatography–mass spectrometry (UHPLC-ESI-HRMS) analysis of the seed extract identified phenolic compounds including ellagic, p-coumaric, and chlorogenic acids, as well as flavonoids such as quercetin, myricetin, and epicatechin. This study provides the first evidence of the hypoglycemic activity of MFSs, offering valuable insights into their phytochemistry and potential therapeutic applications. Full article

Diabetic foot ulcers (DFUs), which affect approximately 15% of individuals with diabetes mellitus (DM), result from complex molecular disturbances involving chronic hyperglycemia, immune dysfunction, and infection. At the molecular level, chronic hyperglycemia promotes the formation of advanced glycation end products (AGEs), activates the AGE-RAGE-NF-κB axis, increases oxidative stress, and impairs macrophage polarization from the pro-inflammatory M1 to the reparative M2 phenotype, collectively disrupting normal wound healing processes. The local wound environment is further worsened by antibiotic-resistant polymicrobial infections, which sustain inflammatory signaling and promote extracellular matrix degradation. The rising threat of antimicrobial resistance complicates infection management even further. Recent studies emphasize that optimal glycemic control using antihyperglycemic agents such as metformin, Glucagon-like Peptide 1 receptor agonists (GLP-1 receptor agonists), and Dipeptidyl Peptidase 4 enzyme inhibitors (DPP-4 inhibitors) improves overall metabolic balance. These agents also influence angiogenesis, inflammation, and tissue regeneration through pathways including AMP-activated protein kinase (AMPK), mechanistic target of rapamycin (mTOR), and vascular endothelial growth factor (VEGF) signaling. Evidence indicates that maintaining glycemic stability through continuous glucose monitoring (CGM) and adherence to antihyperglycemic treatment enhances antibiotic effectiveness by improving immune cell function and reducing bacterial virulence. This review consolidates current molecular evidence on the combined effects of glycemic and antibiotic therapies in DFUs. It advocates for an integrated approach that addresses both metabolic and microbial factors to restore wound homeostasis and minimize the risk of severe outcomes such as amputation. Full article

The beneficial effect of consuming fruits and vegetables in the prevention of chronic non-communicable diseases and healthy aging is well known. This is attributed to food and vegetable antioxidant and fiber content. The aim of this publication is to communicate the results of recent research on pectin in humans, to propose an increased consumption of fruits and vegetables, or their possible use as a food supplement. A comprehensive narrative review was conducted considering recent publications on pectin. The description of starch, pectin, the physicochemical changes caused by pectin, and the effect of pectin on the activity of amylase are reported. Dietary fiber and gut microbiota in human health are also described, with the production of saturated fatty acids with fewer than six carbon atoms. Finally, health effects such as anti-hyperglycemic and anti-hyperlipidemic activities, preventing and controlling obesity and heart disease, are analyzed, as well as other health effects in tumors, the gastrointestinal tract, and immunity. Considering the beneficial effects of pectin in health and the low consumption throughout the world, it is recommended to promote the consumption of fruits and vegetables to increase pectin intake in the human diet. Full article

Amorpha fruticosa L. (Fabaceae) originates from North America and has become an aggressive invasive plant in many parts of the world. It affects the local biodiversity in many negative ways. Our previous in vivo tests of purified extract of A. fruticosa pods for antihyperglycemic activity in streptozotocin-induced diabetic spontaneously hypertensive rats (SHRs) revealed that the oral administration of purified extract of A. fruticosa (100 mg/kg) for 35 days to SHRs caused significant decreases in the systolic pressure, blood glucose levels, and MDA quantity. The aim of this experimental study is to test the glycosidase inhibition of several extracts of A. fruticosa pods. Methods: GC-MS, NMR, and a glycosidase inhibition assay were performed. Results: The results demonstrate strong inhibition of yeast alpha- and almond beta-glucosidases, rat intestinal hexosaminidase, and bovine beta-glucuronidase, but not of some other glycosidases. The activity is probably due at least in part to the presence of iminosugars and iminosugar acids. We here report on further analysis and activity assessments of A. fruticosa pods and leaves collected in Bulgaria, and for the first time discover glycosidase inhibitors, pinitol, and hydroxylated pipecolic acids in the species and more complex iminosugar-like compounds that may all contribute to antidiabetic potential. Hydroxylated pipecolic acids are probable precursors of iminosugars and common in legumes containing them. Considerable chemical variation was observed over four pod collections. Conclusions: A. fruticosa pods and leaves were found to contain a number of compounds that could contribute to the potential antihyperglycemic activities including pinitol and a complex mixture of iminosugar-related compounds derived from pipecolic acids and prolines. The pods and leaves caused potent selective inhibition of glucosidases and hexosaminidases and beta-glucuronidase. The variation between the collections might reflect the sites differing or wide phenotypic versatility allowing the success of the species as an invasive plant. Full article

Gout, a metabolic and autoinflammatory disease, is the most common form of inflammatory arthritis worldwide. Hyperuricemia may result in monosodium urate (MSU) crystals forming and depositing in joints and surrounding tissues, triggering an autoinflammatory response. Effective urate-lowering therapies, as well as anti-inflammatory medications, are used to treat gout. Over the past few decades, new antihyperglycemic drug classes with different modes of action have been added to treat hyperglycemia in type 2 diabetes mellitus (T2DM). Two of these drug classes, sodium–glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), have reduced cardiovascular and renal events and mortality. Several clinical studies have demonstrated that SGLT2 inhibitors possess urate-lowering properties, which may be beneficial for treating gout patients, particularly those with comorbid T2DM. Regarding SGLT2 inhibitors, some researchers have suggested that their benefits are partly explained by their ability to reduce serum urate (SU) levels, probably through increased urinary uric acid excretion. The effect of GLP-1 RA on SU levels and urinary excretion of uric acid in humans is unclear. This paper reviews the mechanisms of action of SGLT2 inhibitors and GLP-1RA, both approved and in development. Additionally, it examines what is known about their structure–activity relationships, uricosuric effects, pharmacokinetic profiles, and adverse effects. Full article