Search Results (352)

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 effects of silk sericin (SS) supplementation on the functionality of chromium picolinate (CrPic) and lipid metabolism were assessed in male Sprague–Dawley rats to determine whether SS improves the bioavailability of CrPic and contributes to beneficial changes in lipid profiles and cardiovascular risk markers. Rats were administered different doses of SS (0, 1, 10, and 100 mg kg⁻¹ body weight (BW)) in conjunction with CrPic (300 µg kg⁻¹ BW) for 8 weeks through oral gavage. Body and organ weights, lipid profiles, glucose levels, chromium (Cr) accumulation, total protein, and adipocyte size were evaluated. Additionally, FTIR analysis was conducted to investigate the binding and release behavior of SS with CrPic. Although body weight and daily feed intake were comparable among groups, a significant increase in pancreas weight and reduction in omentum weight were observed across all CrPic-SS groups. Increased dosages of SS resulted in a significant reduction in triglyceride and plasma glucose levels. All CrPic and CrPic-SS treatments reduced LDL and total cholesterol while increasing HDL. Cr accumulation was elevated in the liver and kidneys of groups administered 10 and 100 mg kg⁻¹ BW of SS, accompanied by a significant increase in total protein levels and a reduction in adipocyte size to less than 50 µm in all rats. FTIR analysis indicated that SS binds to CrPic at pH 2.0 and releases it at pH 7.0, demonstrating pH-dependent delivery similar to the gastrointestinal tract and possibly improved CrPic functionality. These findings indicate that SS improves the bioavailability of CrPic and positively affects lipid metabolism and cardiovascular risk markers in vivo. 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

The escalating global prevalence of obesity underscores the need for effective and sustainable nutritional interventions. Functional foods, especially white kidney beans (Phaseolus vulgaris), show a promising avenue to link fundamental biochemical insights with clinically feasible interventions, supporting their potential as an adjunct dietary strategy for managing and preventing obesity. This review critically examines the mechanistic roles of white kidney bean in weight regulation, which includes suppression of starch digestion, attenuation of postprandial glycemia, modulation of appetite and satiety, and hypolipidemic effects. Clinical and preclinical evidence supports the potential of white kidney bean as a nutraceutical for metabolic health, demonstrating consistent reductions in body fat mass, glycemic excursion, and overall weight. Nevertheless, significant limitations persist, including heterogeneity in trial designs, absence of dose standardization, and inadequate long-term safety assessments. Furthermore, this review addresses food fortification, advancements in supplement formulation, and cooking techniques that enhance both consumer acceptability and the bioactivity of white kidney bean (WKB), along with the significance of regulatory standards to ensure safety and quality. Future research should integrate clinical, molecular and food technology methods to improve the translation of experimental findings into precision nutritional strategies for obesity management. Full article

Aquatic ecosystems are increasingly threatened by multiple anthropogenic stressors, notably climate change and pollution by pharmaceuticals. Global warming is predicted to raise water temperatures by 2–5 °C by the end of the century. As ectotherms, fish are particularly vulnerable due to limited thermal tolerance and temperature-dependent physiology. Pharmaceuticals are introduced into aquatic systems at concentrations ranging from ng·L⁻¹ to µg·L⁻¹, including widely prescribed classes such as antibiotics, hormones, analgesics, antifungals, and neuropsychiatric drugs. This narrative review synthesizes experimental evidence on the interactive effects of warming and pharmaceutical exposure in fish. Thirty-nine peer-reviewed studies published since 2005 were analyzed. The findings indicate that higher temperatures often exacerbate pharmaceutical-induced toxicity, altering oxidative stress, metabolism, reproduction, and behavior. Antibiotic-focused studies showed temperature-dependent acceleration of absorption, distribution, metabolism, and excretion, with shorter half-lives and reduced tissue persistence at higher temperatures. Estrogenic hormones and antifungals have been shown to interact with thermal regimes, disrupting reproductive physiology and skewing sex ratios, particularly in species exhibiting temperature-dependent sex determination. Neuropsychiatric drugs exhibited altered uptake and metabolism under warming conditions, resulting in increased brain bioaccumulation and behavioral alterations affecting ecological fitness. Analgesics and anti-inflammatories remain understudied despite their widespread use, with evidence suggesting synergistic effects on oxidative stress at elevated temperatures. Significant research gaps persist regarding chronic exposures, early developmental stages, ecologically relevant temperature scenarios, and underrepresented or absent drug classes, such as hypolipidemic drugs. Ultimately, broader and integrated approaches are needed to better understand and predict the ecological risks of pharmaceutical pollution in a warming world. Full article

Marine-derived natural products have attracted increasing attention due to their promising pharmacological potential against various diseases. The present study investigated the hypolipidemic properties of the alkaloid caulerpin, a secondary metabolite of green algae of the genus Caulerpa, through an ex vivo approach with Precision-Cut Tissue Slices (PCTSs) of Mytilus galloprovincialis digestive glands. PCTSs were exposed to caulerpin (CAU) (100 µM) and fenofibrate (FFB) (100 µM) for 24, 48, and 72 h. Analyses of molecular and cellular responses pertaining to lipid metabolism suggested a similar mechanism of action between CAU and FFB in marine invertebrate species, resulting in a decrease in neutral lipid content ranging from 50 to 70%. CAU’s hypolipidemic action was not associated with increased prooxidant conditions, and slower metabolism of the natural alkaloid compared to FFB was indicated by the response of biotransformation and excretion pathways. Overall, these findings provide initial insights into the potential valorization of CAU for pharmaceutical and nutraceutical applications, highlighting the need for further investigation into its mechanisms of action, possible side effects, and interactions with other drugs. 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

Artemisia selengensis Turcz. (AST), an edible-medicinal herb, contains multifunctional bioactives. This study investigated the application of AST leaf extract (ASTLE) in beer brewing, focusing on the addition stage and its impacts on fermentation dynamics, flavor profile, and functional properties. Fermentation parameters, bioactive compounds (phenolic; flavonoid), and volatiles (using HS-SPME-GC-MS) were analyzed. In vivo efficacy was assessed in high-fat diet-fed mice supplemented for 8 weeks with beer containing 10% ASTLE (post-primary fermentation), evaluating body weight change, serum lipids, and uric acid levels. It was found that adding ASTLE before primary fermentation promoted yeast activity but increased the risk of excessive diacetyl production. Adding ASTLE after primary fermentation significantly increased total phenolic and flavonoid contents. GC-MS analysis revealed that ASTLE contributed 28 additional volatile compounds, including chrysanthenone and eucalyptol, thereby enriching the beer’s flavor profile and complexity. In mice, beer with 10% ASTLE (post-primary fermentation) reduced body-weight gain, and regulated abnormal blood lipids and serum uric acid levels. Adding ASTLE after primary fermentation optimized fermentation stability, bioactive retention, flavor enhancement, and conferred benefits including body-weight regulation, lipid metabolism improvement, and uric acid control, providing a reference for developing functional beers targeting health-conscious consumers. Full article

Non-alcoholic fatty liver disease (NAFLD) is among the most prevalent liver disorders globally, affecting approximately 25% to 40% of the adult population. Closely associated with metabolic syndrome, obesity, insulin resistance, and dyslipidemia, NAFLD presents a growing burden due to its increasing incidence and high healthcare costs. In this context, the development of effective preventive and therapeutic strategies remains a pressing challenge in modern medicine. This review aims to analyze current scientific evidence on bioactive plant compounds—particularly polyphenols and polyprenols—including their natural sources, mechanisms of action, and potential applications in the prevention and dietary management of NAFLD. A growing body of evidence demonstrates that both polyphenols and polyprenols exert hepatoprotective, antioxidant, anti-inflammatory, and hypolipidemic effects. These compounds modulate signaling pathways implicated in hepatic steatosis and fibrosis, positively influence gut microbiota composition, and affect bile acid metabolism. Studies have confirmed the efficacy of polyphenol-rich foods (naringenin, resveratrol, chlorogenic acid, etc.) and polyprenol-based formulations in reducing body weight and liver steatosis, improving biochemical markers and insulin resistance. The combined application of polyphenols and polyprenols may yield synergistic effects on multiple pathogenic pathways and represents a promising direction for the dietary prevention and management of NAFLD. 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

Objectives: Alpinia japonica (A. japonica) is traditionally used for digestive disorders, but its hypolipidemic mechanisms remain unclear. This study investigated the lipid-lowering effects of its fruit (SJGS), rhizome (SJGJ), and leaf (SJY) extracts, exploring their bioactive constituents and organ-specific mechanisms. Methods: Sprague Dawley rats (n = 8/group) fed a high-fat diet received SJGS, SJGJ, or SJY (200 mg/kg/day) for 4 weeks. Serum lipids (TC, TG), liver enzymes (AST, ALT), and intestinal barrier markers (DAO) were measured. Gut microbiota (16S rDNA sequencing), hepatic histopathology, and ileal tight junction proteins were analyzed. Transcriptomics and qPCR assessed ileal gene expression. LC-MS identified chemical constituents, while network pharmacology predicted compound-target interactions. Results: All extracts significantly reduced serum TC (↓ 27–33%), TG (↓ 29–38%), AST/ALT (↓ 22–30%), and DAO (↓ 35–42%) versus controls (p < 0.05). They improved hepatic steatosis, enhanced intestinal barrier function, and modulated gut microbiota (↑ α-diversity, ↓ Firmicutes/Bacteroidetes ratio). Transcriptomics revealed PPAR signaling as the core pathway: SJGS/SJGJ downregulated fatty acid oxidation genes (ACSL1, ACOX1, ACADM), while SJY upregulated APOA1 (2.3-fold). LC-MS identified 33–48 compounds/part, with seven shared constituents. Network analysis prioritized three flavonoids (pinocembrin, luteolin, galangin) targeting TNF, AKT1, and PPAR pathways. Conclusions: The findings suggest A. japonica extracts ameliorate hyperlipidemia through distinct mechanisms—SJGS/SJGJ may inhibit fatty acid oxidation, while SJY potentially enhances APOA1-mediated clearance. Shared flavonoids likely contribute to these effects via PPAR signaling, supporting its traditional use. This study provides a scientific basis for the sustainable utilization of A. japonica resources. Full article

Background: Obesity, characterized by an abnormal and excessive accumulation of fat, significantly affects health by increasing the probability of chronic diseases and has become a pressing global health issue. Among natural compounds with therapeutic potential, rutin exhibits diverse biological effects, such as antioxidant, anti-inflammatory, and hypolipidemic properties. Objective: The purpose of this work is to evaluate the preventive effects of rutin loaded on chitosan nanoparticles on metabolic and oxidative alterations in male albino rats fed a high-fat diet (HFD). Method: The rats were allocated to four distinct groups: control, HFD, HFD treated with 50 mg/kg rutin, and HFD treated with 50 mg/kg nano-rutin, respectively, for six weeks. Results: Molecular docking analysis revealed that rutin exhibits an inhibitory interaction with PPAR-γ, suggesting its potential role in suppressing adipogenesis and contributing to its preventive effect against obesity. Nano-rutin markedly improved glycemic control, reducing fasting glucose from 161.75 ± 8.37 mg/dL in the HFD group to 133.50 ± 3.55 mg/dL, compared to 92.17 ± 3.53 mg/dL in controls. Serum leptin levels decreased from 28.95 ± 1.06 ng/mL in the HFD group to 15.58 ± 0.65 ng/mL with nano-rutin, approaching the control value of 10.43 ± 0.80 ng/mL. Oxidative stress was also significantly alleviated, as shown by a reduction in malondialdehyde (MDA) from 8.43 ± 0.20 U/µL in HFD rats to 6.57 ± 0.08 U/µL with nano-rutin, versus 1.29 ± 0.13 U/µL in controls. Conclusions: Rutin loaded on chitosan nanoparticles demonstrated protective effects against high-fat diet-induced obesity, mainly through modulation of leptin signaling and oxidative stress pathways. These findings highlight the promise of nano-rutin as a natural agent for preventing metabolic disorders related to obesity. Full article

Background: Atherosclerosis is a chronic vascular disease triggered by lipid accumulation. Auricularia heimuer is rich in various bioactive compounds that have anti-inflammatory, antioxidant, and hypolipidemic properties. The specific beneficial effects of A. heimuer on atherosclerosis and its underlying mechanisms require further investigation. Methods: In this study, ApoE^−/− mice were utilized as models of atherosclerosis induced by a high-fat diet (HFD) to investigate the effects of A. heimuer. Analyses of gut microbiota and serum metabolomics were conducted to elucidate the potential mechanism. Results: In HFD-fed ApoE^−/− mice, A. heimuer significantly inhibited the increase in body weight, regulated lipid levels, and alleviated aortic lesions. A. heimuer also modulated the abundance of intestinal flora such as Akkermansia and Ruminococcus and altered the levels of serum metabolites, including 12(S)-hydroxy-5Z,8Z,10E,14Z-eicosatetraenoic acid (12(S)-HETE) and N-acetyl galactosamine 4-sulfate. Furthermore, A. heimuer alleviated oxidative stress and inflammatory responses, thereby mitigating atherosclerosis via the Nrf2/NF-κB signaling pathway. Conclusions: These findings suggest that A. heimuer may serve as a potential therapeutic strategy for atherosclerosis. Full article