Search Results (2,575)

Background: The global healthcare system faces a significant challenge due to the escalating prevalence of type 2 diabetes, affecting over 10% of the world’s population. Suppression of postprandial hyperglycemia through inhibition of carbohydrate-hydrolyzing enzymes is an effective therapeutic strategy. Although curcumin effectively inhibits α-amylase and α-glucosidase activities, its lower solubility and bioavailability restrict its clinical application. In this study, five mono-carbonyl curcumin analogues (CA1–CA5) were synthesized and evaluated for their antidiabetic potential following selective experimental methods both in vitro, and in vivo. Enhanced delivery for the most potent analogue was achieved through PEGylated graphene oxide (PEG-GO) to overcome the shortcomings of curcumin compounds. Methods: In silico ADME profiling was conducted using SwissADME, and molecular docking studies were performed with AutoDock Vina (v1.5.7) to assess enzyme binding interaction. The synthesized compounds were further evaluated using in vitro α-amylase and α-glucosidase inhibition assays, followed by in vivo blood profile analysis. The most active analogue CA3 (chloro derivative) was loaded onto PEG-GO and characterized using UV–visible spectroscopy, Fourier-transform infrared spectroscopy, and scanning electron microscopy. Results: Among all of the compounds, CA3 exhibits the strongest binding affinity and highest enzyme inhibitory activity, followed by CA2 and CA4. PEG-GO-CA3 demonstrated significantly enhanced biological activity compared to its free form. In vivo studies showed marked improvements in body weight and lipid profile, along with significant reductions in blood glucose, glycated hemoglobin, urea, creatinine, alanine aminotransferase, and aspartate aminotransferase levels over a 28-day treatment period as compared to a diabetic control. Spectroscopic and morphological analyses confirmed successful loading of CA3 onto PEG-GO (27.7–31.5%) with a release profile of 38–57% after 12 and 36 h in a controlled environment at pH 7. Conclusions: These findings suggest that PEG-GO-loaded mono-carbonyl curcumin analogues represent promising therapeutic candidates for the management of T2DM. Full article

Honeysuckle berries (Lonicera caerulea) represent a valuable source of bioactive compounds, primarily flavonoids, and iridoids. This study compared the chemical composition and in vitro antioxidant and antidiabetic properties of resin-purified extracts from ripe, unripe, and unripe lactofermented honeysuckle berries. Polyphenols and iridoids were identified using UPLC-ESI-qTOF-MS/MS and quantified using HPLC-PDA. A total of 6 anthocyanins, 7 phenolic acids, 9 flavan-3-ols, 8 iridoids, 8 flavonols, 3 flavones, and 1 flavanonol were identified in the extracts. The extract from ripe fruits was characterized by a high cyanidin glycoside content (273.59 mg/g) and high iridoid content (138.30 mg/g). The amount of individual iridoids varied among the extracts, with the highest level of loganic acid detected in the unripe fruit extract (39.42 mg/g) and the highest level of sweroside in the ripe fruit extract (55.59 mg/g). Phenolic acid content was approximately twofold higher in extracts from unripe and fermented fruits compared with ripe fruit extracts, suggesting a decrease during ripening, while fermentation did not significantly affect phenolic acid content. Among flavonols, quercetin and isorhamnetin derivatives were identified, with quercetin 3-O-rutinoside being the predominant compound in all extracts. The ripe fruit extract exhibited the strongest radical scavenging activity (in ABTS and DPPH assays), ferric ion-reducing power (FRAP), and α-amylase inhibition, while all extracts exhibited comparable α-glucosidase inhibition. These findings indicate that L. caerulea extracts, especially from ripe fruits, are a rich source of biologically active compounds with potential relevance for managing oxidative stress and hyperglycemia. Full article

Pseudopodospermum szowitzii (DC.) Kuth. a member of the Asteraceae family, grows naturally in the Irano-Turanian phytogeographical area, including Anatolia. In Anatolia, P. szowitsii, known as “goftigoda,” has edible young leaves and roots and is used in folk medicine for antidiabetic and analgesic properties. Nine compounds, including chlorogenic acid and derivatives from the ethyl acetate layer as well as 2,4,6-trimethoxyphenyl-1-O-β-glucopyranoside, 2,4,6-trimethoxyphenyl-1-O-β-apiofuranosyl-(1→6)-β-glucopyranoside, esculetin 6-O-β-glucopyranoside, and esculetin 6-O-β-apiofuranosyl-(1→6)-β-glucopyranoside from the water part of the methanolic extract, were isolated as known compounds. Notably, all esculetin derivatives have been isolated from the Pseudopodospermum for the first time, and among them, three compounds, esculetin 6-O-β-xylosyl-(1→6)-β-glucopyranoside, esculetin 6-O-β-glucopyranosyl-(1→3)-β-glucopyranoside, and esculetin 6-O-β-glucopyranosyl-(1→6)-β-glucopyranoside, were isolated as new esculetin heterosides that have not yet been isolated from any natural sources. The antioxidant activities of the total extract, phases, fractions, and compounds of P. szowitsii were also tested by evaluating their radical-scavenging capacities against DPPH and ABTS radicals. The ethyl acetate phase and the isolated compounds displayed significant antioxidant activity. The most active compound was caffeic acid, with IC₅₀ values of 2.7 µg/mL and 3.4 µg/mL against DPPH and ABTS radicals, respectively, followed by dicaffeoylquinic acid derivatives and their methyl esters. On the other hand, none of the coumarin derivatives exhibited significant radical-scavenging activity. Full article

Background: Tectoridin is a prominent isoflavone glycoside found in herbs such as Belamcanda chinensis (L.) DC and Iris tectorum Maxim. It has drawn increasing research interest due to its promising pharmacological activities. However, no critical review to date has determined whether its broad pharmacological activity stems from binding to specific targets or from the non-specific, broad-spectrum activity commonly associated with flavonoids. This paper provides a comprehensive review of tectoridin, covering its plant sources, pharmacological effects, pharmacokinetics, and toxicity, alongside an in-depth analysis of the mechanisms underlying its pharmacological effects and strategic recommendations for advancing its clinical translation. Methods: A systematic literature search was conducted in PubMed, Web of Science, Google Scholar, SciFinder, and CNKI for publications from 1968 to 2025 using keywords including tectoridin, tectorigenin 7-O-glucoside, traditional uses, ethnopharmacology, pharmacology, bioactive compounds, biological activity, pharmacokinetics and toxicity. Results: Tectoridin exhibits a broad spectrum of pharmacological activities, including anticancer, anti-inflammatory, hepatoprotective, antidiabetic, antioxidant, cardiovascular, and estrogenic effects. Pharmacokinetic studies have shown rapid tissue distribution and slow elimination; the aglycone metabolite tectorigenin often displays enhanced bioactivity, and chemical modifications may further improve efficacy. Toxicity data suggest relative safety in medicinal food contexts, but comprehensive in vivo studies remain limited. Tectoridin shows promise for treating cancer and inflammatory diseases; however, further research is needed to elucidate its molecular mechanisms, clarify toxicity, and optimize bioactivity. Conclusions: This review bridges natural products and modern therapeutics by focusing on tectoridin, highlighting its therapeutic potential, addressing challenges, and offering new perspectives for treating various diseases. Full article

Background/Objectives: The accumulation of unused and expired pharmaceuticals in households is a growing public health concern with implications for patient safety, rational drug use, and environmental health. However, systematic risk characterization integrating clinical and environmental perspectives at the community level remains limited, particularly in low- and middle-income settings. This study aimed to develop and apply a composite risk index, grounded in an eco-pharmacovigilance framework, for the assessment of health risks associated with accumulated household pharmaceuticals in southeastern Mexico. Methods: A cross-sectional study was conducted in 526 randomly selected households using stratified sampling. Guided in-home medication inventories were performed with participant collaboration, and pharmaceuticals were classified according to the Anatomical Therapeutic Chemical (ATC) system. A composite risk index (CRI = Fr × PR) was developed within an eco-pharmacovigilance framework. The frequency of accumulation (Fr) for each therapeutic group was multiplied by a potential risk score (PR) derived through a structured multidisciplinary expert consensus process integrating clinical toxicity, environmental persistence, and antimicrobial resistance potential. Results: A total of 2184 pharmaceutical units were recorded during the household inventories, of which 28.7% were expired. Expired medications were primarily retained rather than actively used, representing a latent risk for inappropriate self-medication and accidental exposure. The therapeutic groups with the highest CRI values were antihypertensives (CRI = 42.3), antidiabetics (CRI = 37.8), and antibiotics (CRI = 31.5), indicating a relatively higher contribution within the composite risk index framework to overall household pharmaceutical risk. These findings highlight priority therapeutic groups driven by the combined effect of high accumulation frequency, distinct accumulation patterns, and intrinsic hazard. Conclusions: Household pharmaceutical accumulation can be characterized using a composite, eco-pharmacovigilance-based approach that integrates exposure and hazard dimensions. The proposed framework functions as a prioritization tool rather than a precise quantitative measure, enabling the identification of therapeutic groups requiring targeted intervention. Findings should be interpreted as indicative of relative risk patterns rather than precise estimates, given the exploratory design and guided data collection approach. The proposed framework provides a practical tool for prioritizing interventions aimed at improving rational drug use, reducing accumulation, and mitigating environmental impact. Further validation in diverse settings is warranted to strengthen its applicability. Full article

Background/Objectives: Pigmented rice is increasingly recognized as a functional food because of its rich phytochemical composition and health-promoting potential. However, local red rice cultivars from the three southern border provinces of Thailand remain insufficiently characterized. This study comparatively evaluated four whole-grain red rice cultivars—Hawm Gra Dang Ngah 59 (HGDN 59), Hawm Mue Lau (HML), Lued Pla Lai (LPL), and Se Bu Kan Tang (SBKT)—for their chemical composition, antioxidant activities, and antidiabetic potential. Methods: Whole-grain rice samples were extracted with 95% ethanol and assessed for extraction yield, total phenolic content, and total flavonoid content. Antioxidant activity was measured using DPPH^•, FRAP, and anti-lipid peroxidation assays, while antidiabetic activity was measured using α-amylase and α-glucosidase inhibition assays. LC-MS/MS-based chemical profiling, pathway classification, PCA-based chemical space analysis, molecular docking against α-glucosidase, and physicochemical/ADMET prediction were also performed. Results: Among the tested cultivars, HGDN 59 showed the most favorable overall profile, with the highest phenolic content, strongest antioxidant activity, and marked α-glucosidase inhibitory activity. LC-MS/MS analysis combined with docking-based screening revealed that HGDN 59 contained several abundant compounds, including ent-Epicatechin-(4α→6)-ent-epicatechin, cinnamtannin A1, apiin, and α-tocotrienol. These compounds exhibited strong binding affinities toward α-glucosidase (−10.7 to −9.6 kcal/mol), comparable to or slightly more favorable than acarbose. ADMET prediction indicated that most polyphenolic compounds exceeded Lipinski’s rule of five, while α-tocotrienol demonstrated favorable absorption property. Conclusions: This is the first study to suggest that HGDN 59 exhibits potential α-glucosidase inhibitory activity in vitro and may serve as a promising functional food candidate for the dietary management of postprandial glycemic response. Full article

The growing interest in plant-derived bioactive secondary metabolites has renewed attention
to grape pomace as a promising source within the context of sustainable and circular
bioeconomy strategies. Its chemically diverse composition, influenced by cultivar, climate,
and processing conditions, has shown a wide range of biological activities, including
antioxidative, anti-inflammatory, antimicrobial, antidiabetic, and anticancer effects.
Several reviews have addressed its composition, bioactivity, extraction, and applications,
but a more integrated understanding of the molecular mechanisms is still needed. This
review synthesizes recent evidence on the mechanistic actions of grape pomace metabolites,
highlighting their involvement in key pathways such as Nrf2-mediated antioxidant
defense, NF-κB-regulated inflammation, AMPK/SIRT1-dependent metabolic regulation,
apoptosis-related signaling, and microbiota-driven phenolic metabolism. It also discusses
challenges related to raw material variability, process standardization, and industrial
scalability, and explores how advances in chemometrics, omics technologies, and datadriven
optimization can support future development. Therefore, it provides an integrated
perspective linking mechanistic insights with technological considerations to advance the
sustainable valorization of grape pomace. Full article

Background: This study investigated the effects of increasing levels of salinity on leaf phytochemical composition and the antioxidant, antidiabetic, and anti-obesity activities. Method: Three quinoa accessions grown under escalating NaCl treatments had their leaves exposed to various chemical analyses. Polyphenols, tannins, and flavonoids were among the phenolic substances whose concentrations were measured. The phenolic chemicals in the water extract were identified using HPLC-DAD-ESI-MS/MS. In vitro and in silico methods were used to measure anti-radical (DPPH), anti-alpha glucosidase, anti-alpha-amylase, and anti-lipase activities. Results: The results showed that water and ethanol, due to their polarity, were the most effective solvents for extracting phenolic compounds. Additionally, salt application led to a dose-dependent increase in total phenols (TPC), flavonoids (TFC), and tannins (CT) across all accessions. The accession DE-1 exhibited the highest contents with average values of 1453.03–4398.36 mg EGA/100 g DW, 322.7–1090.7 mg CAE/100 g DW, and 77.9–335.96 mg CAE/100 g DW of TPC, TFC, and Tannins, respectively. HPLC-ESI-DAD-MS/MS profiling of phenolic compounds led to identifying 18 constituents, including five major compounds (p-coumaric acid, caffeic acid, vanillic acid, p-coumaroyl hexose, and HHDP-galloyl glucose). Except for p-coumaroyl hexose and HHDP-galloyl glucose, which were extensively biosynthesized/accumulated in the salt-tolerant accession DE-1, the remaining phenolic compounds showed irregular evolution depending on accession and salt concentration. Moreover, ethanol and water extracts were evaluated for their anti-radical and enzyme-inhibitory activities. Conclusion: Salt-stressed DE-1 water extract showed strong antioxidant and enzyme inhibitory activities, indicating potential antidiabetic and anti-obesity effects. These activities were confirmed by in silico analysis. Full article

Mogrosides, the primary bioactive compounds of Siraitia grosvenorii, are natural, non-caloric sweeteners with promising therapeutic potential for diabetes. They provide a dual advantage: delivering sweetness without impacting blood glucose levels, while simultaneously exerting beneficial antidiabetic effects. This review systematically synthesizes current knowledge on mogrosides, covering their extraction methods, metabolic pathways, and underlying antidiabetic mechanisms. We first detail key extraction techniques and examine their metabolic fate, which is primarily characterized by gut microbiota-mediated deglycosylation leading to the formation of mogrol. Subsequently, the antidiabetic efficacy of mogroside-rich extracts and pivotal monomeric derivatives is critically evaluated, with an emphasis on mechanistic insights such as AMP-activated protein kinase (AMPK) pathway activation, anti-inflammatory and antioxidant activities, immunomodulatory effects, and the regulation of gut microbiota. It is important to note that due to the limitation of clinical trial data, most of the evidence reviewed derives from in vitro studies or animal models. Finally, their emerging role as functional ingredients within the food industry was discussed. Collectively, this review aimed to establish a robust scientific foundation for the development of mogrosides as safe, plant-derived sweeteners endowed with enhanced health-promoting properties for the prevention and management of diabetes. Full article

Background/Objectives: The most abundant flavonoid, quercetin, which is mostly found as glycosides, is widely distributed in plants. Quercetin is rapidly metabolized, having a short half-life in the blood circulation, and forms its conjugates by undergoing ring cleavage of the benzopyranone ring system. Despite its fast clearance in the body, quercetin was demonstrated to have clinically anti-inflammatory, cardioprotective, antidiabetic, and anti-obesity activities. This study aimed to determine whether quercetin itself or its metabolites are responsible for these activities. Methods: We performed molecular docking of 27 metabolites, including quercetin itself, against ten inflammation-related proteins in silico. We then conducted microscale thermophoresis (MST) of selected metabolites towards the NLRP3 inflammasome. Results: Overall, Phase II metabolites yielded better binding energies compared to the metabolites formed by degradation. MST results revealed that isorhamnetin, the 4-O-methylated metabolite of quercetin, gave the best results, with a binding affinity (K_D value) of 16.12 ± 5.16 µM, even better than quercetin itself, which has a binding affinity of 44.84 ± 4.21 µM. Glucuronide metabolites of quercetin (isorhamnetin 3-O-glucuronide, quercetin 7-O-glucuronide, and quercetin 3-O-glucuronide) were found to bind to the inflammasome protein with low binding affinities, whereas small degradation products (hippuric acid and 3,4-dihydroxytoluene) did not bind at all. Conclusions: These results suggest that Phase II metabolites, specifically isorhamnetin, may contribute more significantly to the biological activity of quercetin than the parent compound, however, degradation products appear inactive. Full article

Background: Diabetes mellitus is a metabolic disturbance characterized by chronic hyperglycemia, which stems from defective secretion and/or action of insulin. D-Limonene has been studied for the confirmation of its antidiabetic and antioxidant effects. This paper aims to investigate the antidiabetic and antioxidants effects of D-Limonene in an experimental model of DM1. Methods: Female Wistar rats (180–250g) received streptozotocin (STZ, 45 mg/kg) intraperitoneally. Animals with capillary glycemia ≥ 250 mg/dL were considered diabetic. D-Limonene at oral doses of 12.5 mg/kg, 25 mg/kg and 50 mg/kg was administered during 28-day treatment. Water and food intake, weight gain and capillary glycemia were evaluated. At the end of the treatment, the following biochemical parameters were assessed: serum glucose, HbA1c, urea, creatinine, AST, ALT, GGT, ALP and albumin. The oxidative stress markers were determined in plasma, erythrocytes, and aortic homogenates: malondialdehyde, nitrite, myeloperoxidase, superoxide dismutase and catalase. Results: D-Limonene (25 and 50 mg/kg) significantly reduced serum glucose, HbA1c, AST, ALT, GGT and ALP when compared to DC, as well as plasma MDA and nitrite concentrations. Interestingly, D-Limonene (25 and 50 mg/kg) decreased both plasma and aortic myeloperoxidase activities, as well as increased both erythrocytic and aortic catalase activities. Conclusions: These findings, besides a marked D-Limonene-induced hypoglycemic effect, pave the way for further studies comprising a multi-target treatment by providing benefits on hepatic and vascular complications related to the diabetic condition. Full article

Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for neurodegenerative diseases. Metformin has been found to have neuroprotective effect, in addition to antidiabetic function. Our recent studies have identified that metformin ameliorates Cd neurotoxicity via blocking ROS-dependent PP5/AMPK-JNK signaling pathway. Here we further show that metformin protected PC12 cells and primary neurons from Cd-poisoning by mitigating Cd-induced increases in ATG5/LC3-II/p62 levels and autophagosomes. Knockdown of ATG5 dramatically potentiated the inhibitory effects of metformin on Cd-induced LC3-II, cleavage of caspase-3, accumulation of autophagosomes and apoptosis in PC12 cells. Addition of chloroquine (CQ) strengthened the basic and Cd-elevated ATG5/LC3-II/p62 levels, autophagosome accumulation and cell apoptosis, whereas metformin powerfully blocked the events, implying a metformin-promoted autophagic flux-dependent mechanism involved. Further research revealed that metformin prevented Cd-induced autophagic flux impairment and cell apoptosis, which was attributed to restraining Cd inactivation of AMPK. This is supported by the findings that activation of AMPK with AICAR or ectopic expression of constitutively active AMPKα (AMPKα-ca) reinforced the inhibitory effects of metformin on Cd-evoked ATG5/LC3-II/p62/autophagosomes and apoptosis in PC12 cells and/or primary neurons. Taken together, the results indicate that metformin protects neuronal cells from Cd-induced autophagic flux impairment-dependent apoptosis by activating AMPK. Our studies highlight that metformin has a great potential for prevention of Cd toxicity related to neurodegenerative diseases. Full article

Helichrysum odoratissimum (L.) Less. is used as a traditional medicine in South Africa to treat tuberculosis, abdominal pains, heartburn, coughs, colds, female sterility, eczema and wounds. In Uganda, the leaves are used to treat dental/oral diseases. This review aims to provide detailed information on the traditional uses, essential oils, phytochemistry, in silico studies, and pharmacological studies and propose possible future research directions on this widely investigated species. The data was gathered from various online electronic databases such as Science Direct, Scopus, Google Scholar, Web of Science, SciFinder, Wiley Online, SpringerLink, and PubMed. Reports on the essential oil composition of H. odoratissimum showed the dominance of monoterpenoids and sesquiterpenoid compounds. Several studies also reported the isolation of the non-volatile compounds, which were mainly flavonoids and terpenes. The species has been reported to have pharmacological activities such as antimicrobial, antimycobacterial, antioxidant activity, antidiabetic, antiproliferative, anti-inflammatory activity and antityrosinase activity. The most important study on H. odoratissimum was a clinical trial in human participants in South Africa addressing its in vivo irritancy potential. However, further research on the clinical and scientific aspects is needed to justify some of its other medicinal uses. Full article

Plants of the genus Salacia (Celastraceae) have long been used in traditional medical systems of South and Southeast Asia for the management of diabetes and related metabolic disorders. Modern phytochemical and pharmacological studies have confirmed the antidiabetic potential of several Salacia species, leading to the identification of a distinctive group of sulfur-containing sugars as their principal bioactive constituents. Salacinol, neosalacinol, kotalanol, neokotalanol, and related analogues represent a novel class of thiosugar sulfonium compounds that act as potent and selective α-glucosidase inhibitors, providing a clear mechanistic basis for their glucose-lowering effects. Simpler thiosugars, such as 5-thiomannose, further contribute to the overall metabolic activity of Salacia extracts and may serve as biosynthetic or functional precursors. Beyond Salacia, sulfur-containing natural products are widespread in nature and perform diverse biological roles. In particular, the genus Allium is well known for producing organosulfur compounds, including thioethers and polysulfides, which exhibit antidiabetic, hypolipidemic, antioxidant, and cardioprotective activities. In a different context, sulfur-containing hopanes have been identified in sediments and petroleum as products of early diagenetic sulfurization of bacterial hopanoids. Although these compounds have been studied primarily as geochemical biomarkers, recent QSAR/PASS analyses suggest that sulfur hopanes may also possess biologically relevant activities, particularly related to metabolic and cardiovascular regulation. Recent PASS-based QSAR evaluations of Salacia-derived thiosugars and sulfur hopanes predict significant antidiabetic activity, including potential type 2 diabetes-related pharmacological effects, supported by predicted α-glucosidase inhibitory, hypoglycemic, hepatic, and gastrointestinal activities. Collectively, these findings highlight sulfur-containing natural products from both plant and sedimentary sources as chemically diverse yet functionally convergent scaffolds with promising potential for the development of functional foods and therapeutic agents targeting metabolic disorders. Full article

The integration of rooted plant flour into traditional noodle matrices, such as rice noodles and qingke noodles, represents a novel approach to enhancing the nutritional and sensory profiles of staple foods. This study investigates the volatile flavor components and functional compounds derived from rooted plant flours, including Gongmi “tribute rice”, qingke “highland barley” flour, kudzu vine flour, Gastrodia elata blume flour, dried ginger flour, and fishwort root flour, when incorporated into rice and qingke noodles. The novelty of this research lies in its comprehensive analysis of how these flours influence not only the nutritional and textural properties but also the volatile organic compounds (VOCs) that define sensory acceptance and health benefits. Using advanced gas chromatography mass spectrometry (GC-MS), we identified key VOCs, such as esters, aldehydes, and terpenes, which contribute to unique flavor profiles like umami, sweetness, and earthy notes in fortified noodles. Additionally, the study highlights the best functional compounds for health, including polyphenols, resistant starch, and polysaccharides, which demonstrate significant antioxidants, anti-inflammatory, and cholesterol-lowering properties. For instance, highland barley enriched flour exhibited high levels of phenolic compounds and carotenoids, which correlated with improved antioxidant activity and a reduced glycemic index. Similarly, Gongmi flour contributed elevated levels of γ-aminobutyric acid (GABA) and rutin, enhancing the rice noodles’ potential to manage metabolic diseases and support cardiovascular health. Molecular docking analyses predicted strong interactions between key volatile compounds (e.g., 3-dihydro-1, 3-trimethyl-33-phenyl-1H-indene) and metabolic targets like ACE and SGLT1, suggesting mechanisms for their cardioprotective and anti-diabetic effects. This research provides a groundbreaking framework for developing next generation functional foods by leveraging rooted plant flours to bridge the gap between sensory appeal and health efficacy, offering strategic insights for personalized nutrition and sustainable food production. Full article