Search Results (280)

Type 2 diabetes mellitus (T2DM) is an endocrine–metabolic disorder characterized by pancreatic islet dysfunction-induced hyperglycemia, which triggers hepatic injury, intestinal microbiota dysbiosis, and systemic complications. Fagopyrum tararicum seeds exhibit various biological activities, including antioxidant, hypolipidemic, and antihypertensive effects. However, there is limited research exploring how supernatants derived from the water extraction–ethanol precipitation of Fagopyrum tararicum seeds (SWEPFT) modulate the intestinal microbiota and their potential link to T2DM. This study evaluates SWEPFT’s effects on hyperglycemia and intestinal microbiota in T2DM mice. After a 4-week therapeutic period, SWEPFT markedly ameliorated hyperglycemia, as evidenced by reduced body weight (BW), fasting blood glucose (FBG), and glycated serum protein (GSP) and improved insulin sensitivity/resistance indicators (HOMA-IS/IR) and β-cell function (HOMA-β). Furthermore, the levels of both Akt1 and Slc2a2 transcription displayed notable enhancement. SWEPFT-H (high-dose SWEPFT) exhibited superior effects to SWEPFT-L (low-dose SWEPFT) in improving BW, FBG, and HOMA-IS. Moreover, SWEPFT modulated the intestinal microbiota by decreasing the Firmicutes/Bacteroidetes ratio, augmenting the proportion of Intestinimonas and Ruminiclostridium, and increasing the short-chain fatty acid content. A correlation analysis identified Candidatus_Arthromitus, Anaeroplasma, Candidatus_Stoquefichus, and Harryflintia as potential T2DM biomarkers linked to glycemic regulation. These findings elucidate SWEPFT’s critical role in microbiota modulation and hyperglycemia alleviation, providing a novel perspective for T2DM pathogenesis research and therapeutic development. Full article

Metabolic syndrome, a collective term for lipid and carbohydrate disorders in the organism, is the primary cause of type 2 diabetes mellitus development and its associated systemic side effects. The current approach for the medical treatment of this condition usually requires multiple medications, targeting multiple pathophysiological pathways. A promising drug class in that regard is the dual PPARα/γ agonists, which impact both lipid and carbohydrate metabolism, yet to this day the vast majority of them have not passed the clinical trials, due to potential toxicity risks. In the present study we synthesized and tested a series of monoterpene-substituted (S)-2-ethoxy-3-(4-(4-hydroxyphenethoxy)phenyl)propanoic acids as potentially effective and safe novel dual PPARα/γ agonists. In vitro studies showed that nearly all of the tested compounds were sufficiently active towards both PPARα and PPARγ. All compounds were tested in vivo, using C57BL/6 A^y/_a mice with T2DM symptoms, in order to evaluate their impact on carbohydrate and lipid metabolism. The most promising of them was found to be compound 5h, containing a cumin fragment, which showed pronounced hypoglycemic activity by boosting tissue insulin sensitivity and hypolipidemic effects manifested by reductions in fat tissue mass and blood triglyceride levels, while simultaneously displaying a relatively safe profile. Full article

Background: Chronic diseases are leading causes of morbidity and mortality worldwide and their prevalence is increasing due to aging and lifestyle factors. A central element in their pathophysiology is chronic low-grade inflammation, linking metabolic, cardiovascular, neurodegenerative, and proliferative disorders. In this context, Opuntia dillenii, a cactus species traditionally used in folk medicine, has attracted considerable scientific interest due to its promising nutraceutical potential. Methods: This systematic review was conducted through a PRISMA-guided literature search using PubMed, Scopus, and Web of Science, identifying 45 studies that analyze the phytochemical composition and biological activity of O. dillenii. Results: The compounds highlighted include betalains, polyphenols, flavonoids, and polysaccharides that exhibit potent anti-inflammatory and analgesic effects by modulating key inflammatory mediators. In addition, O. dillenii demonstrates antiproliferative activity, inducing apoptosis and inhibiting tumor growth in various in vivo models, suggesting a potential role in cancer prevention and as a complementary therapy. The cactus also exhibits antiatherogenic and hypotensive effects, as well as hypolipidemic and antidiabetic properties by improving lipid profiles, reducing serum cholesterol and triglycerides, and enhancing insulin sensitivity. Furthermore, its protective actions against tissue damage extend its therapeutic potential. Antimicrobial properties have also been reported, reinforcing its value as a functional food. Conclusions: Taken together, the evidence supports the use of O. dillenii as a versatile nutraceutical resource with a low toxicity profile, capable of contributing to the prevention and treatment of various chronic inflammatory and metabolic diseases. Nevertheless, human clinical trials are needed to validate these findings and explore their full therapeutic utility. Full article

The development of plant-based synbiotic beverages is gaining increasing attention as consumers seek sustainable, functional alternatives to dairy products. This preliminary study investigated the fortification of tibicos (water kefir) with lemon catnip (Nepeta cataria var. citriodora) hydrolate, an aromatic distillation byproduct rich in bioactive terpenoids. After 72 h-fermentation of tibicos, physicochemical, microbiological, health-promoting and sensory parameters were evaluated. Both control and fortified beverages exhibited typical fermentation kinetics, including a decrease in pH, reduction of soluble solids, and accumulation of organic acids. Lactic acid bacteria count remained stable, while yeast proliferation was slightly reduced in the hydrolate-fortified sample, consistent with the known yeast-sensitive nature of certain hydrolate-derived terpenoids. Importantly, hydrolate fortification significantly enhanced antioxidant capacity (DPPH: +34%; ABTS: +39%; RP: +38%). Enzyme-inhibitory activities also increased significantly in the hydrolate-fortified samples (α-Amylase and α-Glucosidase inhibition rates increased by 9% and 11%, respectively). ACE inhibition similarly increased from 32% to 44%, indicating an enhanced antihypertensive potential. HMG-CoA reductase inhibition increased from 31% to 42%, showing improved hypolipidemic activity. Sensory evaluation indicated improved sensory acceptability, imparting citrus–floral notes that balanced the acidic profile of tibicos. These findings highlight the potential of valorizing lemon catnip hydrolate as a functional fortifier in non-dairy synbiotic beverages. Full article

Background and Objectives: This study investigated the antioxidant, lipid-lowering, and hepatoprotective effects of two fenugreek seed varieties, Trigonella foenum-graecum (TFG) and Trigonella corniculata (TC), and analyzed their bioactive potential using various solvents, doses, and biochemical parameters. Materials and Methods: Antioxidant analyses, including ferric-reducing antioxidant power (FRAP), total phenolic content (TPC), and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assays, were conducted, and interventional studies were performed on rats divided into groups receiving disease + standard basal diet (G₀), standard basal diet only (G₁), and disease + standard basal diet supplemented with TC or TFG at 400 mg/kg/day (G₂, G₃) and 800 mg/kg/day (G₄, G₅). Biochemical blood tests assessing lipid profiles and liver function parameters, coupled with histopathological examination of the liver and heart tissues, were also performed. Results: Antioxidant assessments indicated that TFG exhibited greater free radical scavenging ability, higher total phenolic content, and stronger ferric-reducing power than TC did. In the in vivo experiments, both TFG and TC significantly enhanced lipid profiles by reducing total cholesterol, low-density lipoprotein cholesterol (LDL-c), very-low-density lipoprotein cholesterol VLDL-c, and triglycerides while boosting high-density lipoprotein cholesterol (HDL-c) levels (p < 0.001). Liver function tests indicated significant decreases in bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels with dose and plant effects, particularly at 800 mg/kg (G₅). Histopathological examination revealed that TFG at a dose of 800 mg/kg led to an almost normal liver structure and intact myocardial fibers with minimal inflammation, whereas TC groups displayed slight vacuolation of hepatocytes and some inflammatory responses. Conclusions: In conclusion, TFG shows the superior functional food properties of TFG in managing oxidative stress and hyperlipidemia in comparison to TC. Future studies should aim to elucidate the molecular mechanisms, optimize dosing regimens, and evaluate long-term safety and efficacy to support clinical applications. Full article

Background/Objectives: Vincamine is an indole alkaloid initially isolated from plants of the Vinca genus and has previously been demonstrated to have antioxidant, hypoglycemic, and hypolipidemic activities. Vinpocetine, a synthetic derivative of vincamine with an enhanced pharmacological profile, has demonstrated promising antiproliferative properties. While previously reported vinpocetine derivatives have undergone extensive investigation for their pharmacological properties, the role of the E-ring ethyl ester in the antiproliferative properties of compounds with this scaffold has not yet been fully described. Methods: Here, the antiproliferative activity of two vinpocetine analogs with modifications at the E-ring was evaluated through cell viability and LDH assays, and their mechanism of action was investigated through cell cycle analysis, apoptosis detection, and reporter assays for Wnt-1, NF-κB, and STAT3 signaling. Results: Cell viability assays revealed that reduction of the ethyl ester to an alcohol exhibited strong dose-dependent antiproliferative activity across five mammalian cell lines, but did not induce significant markers of apoptosis or necrotic death as determined by FITC/Annexin V and cell cycle flow cytometry, respectively. Through label-free cell imaging, we found the antiproliferative activity of vinpocetine alcohol to be correlated with a decrease in membrane integrity in treated cells. We further observe that both analogs exhibit dose-dependent modulation of TCF/LEF, NF-kB, and STAT3 reporter cells, which appears to be coupled with trends in antiproliferative activity. Conclusions: Altogether, this work demonstrates the potential for E-ring modifications of vinpocetine as antiproliferative agents. Full article

Background/Objectives: Cardiovascular diseases remain the leading cause of mortality worldwide. According to the World Heart Federation, more than 500 million people were living with cardiovascular diseases in 2021. In this context, the use of medicinal plants has become increasingly widespread in populations as a preventive strategy against cardiovascular disorders. Foeniculum vulgare Mill., commonly known as fennel, is an aromatic and medicinal plant recognized for its beneficial properties in the treatment of various ailments, due to its richness in bioactive compounds. This review aims to summarize and analyze the cardiovascular activities of this plant, based on experimental evidence, and to provide an updated overview of its phytochemical composition and safety profile. Methods: A comprehensive literature search was conducted using databases including PubMed, Scopus, Web of Science, and Google Scholar, encompassing all publications available up to 2024. This search included research articles, reviews, mini-reviews, and clinical studies published in English. Exclusion criteria comprised publication types such as letters, conference abstracts, unpublished theses, and non-peer-reviewed reports. Studies were also excluded if they did not specifically address Foeniculum vulgare Mill. or its cardiovascular activities. All studies were screened according to predefined inclusion and exclusion criteria, and relevant data were systematically extracted and analyzed to synthesize current knowledge on the cardiovascular activities, mechanisms of action, phytochemical composition, safety, and potential drug interactions of Foeniculum vulgare Mill. Results: Numerous in vitro and in vivo studies have demonstrated that Foeniculum vulgare Mill. exhibits a wide range of activities beneficial for cardiovascular health. These include antihypertensive, cardioprotective, vasorelaxant, anti-inflammatory, antioxidant, diuretic, hypotensive, hypolipidemic, antiplatelet, and anticoagulant effects. Such pharmacological actions are largely attributed to its rich phytochemical composition, particularly its volatile oils (e.g., trans-anethole, fenchone), flavonoids (e.g., quercetin, kaempferol), and phenolic acids (e.g., p-coumaric acid, ferulic acid). Most studies report no significant signs of toxicity. Conclusions: Foeniculum vulgare Mill. emerges as a promising medicinal plant for the prevention and management of cardiovascular diseases, owing to its multifaceted beneficial effects and its favorable safety profile. However, potential interactions with cardiovascular drugs and the current limitations of existing studies highlight the need for further clinical research to fully establish its therapeutic potential. Full article

This study systematically analyzed the multidimensional effects of Lactobacillus fermentation on Pueraria lobata (PL) and investigated the potential mechanisms underlying its hypolipidemic activity. Results indicated that fermentation significantly increased the total acid content from 1.02 to 3.48 g·L⁻¹, representing a 2.41-fold increase. Although slight reductions were observed in total flavonoids (8.67%) and total phenolics (6.72%), the majority of bioactive components were well preserved. Other antioxidant capacities were retained at >74.71% of baseline, except hydroxyl radical scavenging. Flavor profiling showed increased sourness and astringency, accompanied by reduced bitterness, with volatile compounds such as β-pinene and trans-2-hexenyl butyrate contributing to a distinct aromatic profile. Untargeted metabolomics analysis revealed that fermentation specifically enhanced the abundance of low-concentration isoflavone aglycones, including daidzein and genistein, suggesting a compositional shift that may improve hypolipidemic efficacy. Integrated network pharmacology and computational modeling predicted that eight key components, including genistein, could stably bind to ten core targets (e.g., AKT1 and MMP9) primarily through hydrogen bonding and hydrophobic interactions, potentially regulating lipid metabolism via the PI3K-AKT, PPAR, and estrogen signaling pathways. This study reveals the role of Lactobacillus fermentation in promoting the conversion of isoflavone glycosides to aglycones in PL and constructs a multi-dimensional “components-targets-pathways-disease” network, providing both experimental evidence and a theoretical foundation for further research on the lipid-lowering mechanisms of fermented PL and the development of related functional products. Full article

Nitric esters are among the compounds that can liberate nitrogen monoxide (NO) in the organism. Due to the vasodilatation caused by nitrogen monoxide, NO-donors have been shown to protect endothelial function, acting as vasodilators, promoting efficient oxygen supply to tissues, to lower blood pressure, and to inhibit platelet aggregation. Incorporation of a NO-liberating moiety in the structure of non-steroidal anti-inflammatory drugs results in anti-inflammatory agents that are safer for the gastrointestinal system. In this research, ibuprofen and naproxen, two commonly applied non-steroidal anti-inflammatory drugs (NSAID), non-selective inhibitors of cyclooxygenases, were used to design novel anti-inflammatory agents able to release NO in the organism. Thus, the NSAIDs were amidated with beta-alanine and L-proline, which were able to incorporate the 2-nitro-oxyethyl moiety as the NO donor. The resulting compounds were anti-inflammatory agents, found to be more potent than the mother drugs, demonstrating remarkable inhibition of cyclooxygenase-2 over cyclooxygenase-1 and the ability to release NO in vitro. Furthermore, two of the most active anti-inflammatory compounds proved to be effective hypolipidemic agents, decreasing plasma total cholesterol, triglycerides, and LDL-cholesterol in hyperlipidemic rats significantly. The most effective compound in all the above tests was the ibuprofen derivative 5, which inhibited COX-2 by 95%, decreased inflammation by 73%, and reduced all lipidemic indices by more than 50%. Furthermore, docking experiments of compound 5 on the active sites of COX-1 and COX-2 showed that it interacts intensely with the binding site of COX-2, and the binding energy is equivalent to that of the relevant to celecoxib selective COX-2 inhibitor 4-[5-(4-bromophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (SC-5580). In conclusion, the performed structural modifications resulted not only in the improvement of the anti-inflammatory activity, compared with the parent NSAID, but also acquired strong hypolipidemic activity. Thus, the combination of structural characteristics resulting in a decrease in lipidemia, with possible inhibition of atherosclerosis, due to their anti-inflammatory activity and vasodilatation ability, via the liberated NO, may constitute a useful rationale for new compounds. Full article

Nelumbinis folium (N. folium) exhibits hypolipidemic effects and shows great potential for application in lipid-lowering drugs and healthcare products. This study aimed to investigate the mechanism underlying the hypolipidemic effects of the alkaloid fraction of N. folium (AFN). Animal experiments demonstrated that AFN significantly reduced blood lipid levels and ameliorated liver damage in hyperlipidemic mice. RNA-seq analysis identified 26 reverse-regulated differentially expressed genes (DEGs), which were primarily involved in the PPAR signaling pathway, fat digestion and absorption, and fatty acid degradation. Using UPLC-MSⁿ, 30 plasma-absorbed components were identified, including 13 prototype alkaloids. Among these, three key active components—nuciferine, N-nornuciferine, and N-methylisococlaurine—were screened via network topology analysis. Molecular docking revealed strong binding affinities between these compounds and key targets. The results showed that N-methylisococlaurine bound to SLC27A4 and CPT1A with strong affinity, while nuciferine and N-nornuciferine bound to ACADVL and PPARA. RT-qPCR results confirmed that AFN modulates the expression of FABP1, SLC27A4, PPARA, CPT1A, ACAA2, APOC3, and APOA4. These findings suggest that AFN exerts its hypolipidemic effects through multi-component, multi-target, and multi-pathway mechanisms. Full article

Honeybee brood biopeptides (HBb-Bps) are a novel source of bioactive compounds with potential health benefits. In this study, HBb-Bps were conjugated with honey via a Maillard reaction and their physicochemical properties, digestive stability, antioxidant capacity, and anti-obesogenic effects were evaluated. Simulated gastrointestinal digestion revealed significantly enhanced resistance after conjugation, with the residual content increasing from 46.99% for native HBb-Bps to 86.12% for the honey-conjugated forms; furthermore, antioxidant activity was largely preserved according to the DPPH and ABTS assays. In the in vivo experiments, 30 male BrlHan: WIST@Jcl (GALAS) (Wistar) rats were fed a high-fat diet (HFD) to induce obesity and orally administered honey-conjugated HBb-Bps at doses of 200, 500, or 1000 mg/kg body weight for 16 weeks. The highest dose led to significant reductions in body weight gain, the Lee index, and body mass index. The serum lipid profiles markedly improved, with decreases in the total cholesterol, triglyceride, and LDL levels, as well as cardiovascular risk indices. Furthermore, fecal analysis showed increased levels of short-chain fatty acids, particularly butyrate. These changes suggest enhanced gut microbial activity; however, the prebiotic effects were inferred from the SCFA profiles, as the gut microbiota composition was not directly analyzed. In conclusion, honey-conjugated HBb-Bps improve gastrointestinal stability and exhibit antioxidant, hypolipidemic, and gut-modulating effects, supporting their potential use as functional ingredients for managing diet-induced metabolic disorders. Full article

Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate the effects of cumin and fennel EO nanocapsules in a mouse model of depression caused by a high-fat diet (HFD) and chronic mild stress (CMS) using both in silico and in vivo studies. The cumin and fennel EOs were extracted, analyzed by GC-MS, and encapsulated in nano-form using gum Arabic and maltodextrin as wall materials. The freeze-dried nanocapsules were evaluated in HFD/CMS-treated mice. Molecular docking was used to examine the significance of the oils’ compounds in blocking the active sites of hydroxymethylglutaryl-CoA (HMG-CoA) and indoleamine 2,3-dioxygenase (IDO). According to the molecular docking results, the interactions between EO components and HMG-CoA or IDO indicate that these EOs may have hypercholesterolemic and antidepressive effects. Cumin and fennel EO nanocapsules showed hypolipidemic, antioxidant, and anti-inflammatory effects in vivo. This was demonstrated by the down-regulation of oxidants (ROS, MDA, and NO) and inflammatory markers (TLR4, TNF-α, and IL-6) in the brain, changes in lipid profile parameters, and the up-regulation of antioxidant enzymes (SOD, CAT, and GSH). The in silico and in vivo outputs revealed the potential preventive impact of cumin and fennel EO nanocapsules against depression-like states in the mouse model through the prevention of dyslipidemia, neuroxidation, and neuroinflammation. More human studies are needed to fully understand the antidepressive effects of cumin and fennel EO nanocapsules. Full article

Due to the limited scientific exploration of Argania spinosa (L.) skeel husk, this study presents the first investigation of the metabolite profile of methanol and acetone extracts analyzed by liquid chromatography coupled with electrospray ionization and high-resolution multistage mass spectrometry (LC-ESI/HRMSMS). A total of 43 compounds, including hydroxycinnamic acid and flavonoid derivatives, saponins, and triterpenic acids, were identified, some of which have not been previously reported in this species. The total phenols (TPC) and flavonoids (TFC) content were spectrophotometrically determined. A multi-target approach was applied to investigate the antioxidant potential using 1,1-Diphenyl-2-picrylhydrazyl (DPPH), 2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), β-carotene bleaching, and Ferric Reducing Ability Power (FRAP) tests. Carbohydrate hydrolyzing enzymes and lipase inhibitory activities were also assessed. The acetone extract exhibited the highest TPC and TFC values, resulting in being the most active in β-carotene bleaching test with IC₅₀ values of 26.68 and 13.82 µg/mL, after 30 and 60 min of incubation, respectively. Moreover, it was the most active against both α-glucosidase and α-amylase enzymes with IC₅₀ values of 12.37 and 18.93 µg/mL, respectively. These results pointed out that this by-product is a rich source of bioactive phytochemicals potentially useful for prevention of type 2 diabetes and obesity. Full article

Based on the traditional use of Alchemilla L. species for the treatment of diabetes, the effect of the methanol extract of Alchemilla viridiflora (AVM) on enzyme activity in vitro and its impact on blood glucose levels in vivo were investigated. Diabetes was induced in male Sprague-Dawley rats using streptozotocin. AVM was administered to both normal and STZ-diabetic rats for 20 days at three different doses. Blood glucose levels and body weights of the treated animals were monitored throughout the experiment. After 20 days, serum insulin, cholesterol, triglycerides, and high- and low-density lipoproteins were measured. In addition, a histological analysis of the pancreas was performed. The AVM demonstrated inhibitory effects on the activities of all tested enzymes. In the in vivo experiment, a statistically significant reduction in body weight was observed in the AVM-treated animals at all three doses compared with the normal control group. Notably, a dose of 200 mg/kg significantly decreased blood glucose levels on both the 10th day and 20th day (p < 0.05). However, the extract showed no statistically significant effects on the tested biochemical parameters. Overall, the results of this study suggest that AVM has potential for the treatment of hyperglycemia associated with diabetes and obesity. Full article

The advancement of modern lifestyles has precipitated excessive consumption of energy-dense foods, driving the escalating global burden of lipid metabolism dysregulation-related pathologies—including obesity, type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disorders—which collectively pose a formidable challenge to global public health systems. The almond hull, as a by-product of almond processing, is rich in polyphenolic compounds with demonstrated antioxidant, anti-inflammatory, and lipid-lowering potential, though its precise hypo-lipidemic mechanisms remain elusive. In this study, polyphenols were extracted from almond hulls using 50% ethanol with ultrasound-assisted extraction, followed by preliminary purification via solvent partitioning. The ethyl acetate fraction was analyzed by liquid chromatography–mass spectrometry (LC-MS). Network pharmacology and molecular docking were employed to investigate the interactions between key bioactive constituents (e.g., quercetin, baicalein, and kaempferol) and targets in lipid metabolism-related pathways. Molecular dynamics (MD) simulations further evaluated the stability of the lowest-energy complexes. Results revealed that the ethyl acetate fraction exhibited potent pancreatic lipase inhibitory activity (IC50 = 204.2 µg/mL). At 0.1 mg/mL after 24 h treatment, it significantly reduced free fatty acids (FFAs)-induced intracellular triglyceride accumulation (p < 0.01) and enhanced cellular antioxidant capacity. Network pharmacology and in vitro studies suggest almond hull extract modulates PI3K-AKT signaling and improves insulin resistance, demonstrating lipid-lowering effects. These findings support its potential in functional foods and pharmaceuticals, though further in vivo validation and mechanistic investigations are required. Full article