Search Results (499)

Ruscus aculeatus L. (butcher’s broom), a member of the Asparagaceae family, is a perennial shrub native to the Mediterranean and Black Sea regions and naturalized in parts of Europe and North America. Traditionally, the rhizome and root of this species have been employed in folk medicine for the treatment of venous insufficiency, hemorrhoids, edema, and various dermatological and urinary ailments. These therapeutic applications are attributed primarily to the presence of steroidal saponins such as ruscogenin and neoruscogenin, as well as flavonoids and other bioactive compounds. In recent decades, R. aculeatus extracts have been incorporated into numerous pharmaceutical and cosmetic preparations, particularly those intended to improve venous tone, reduce swelling, and alleviate symptoms of chronic venous disorders. However, despite its widespread use, studies regarding R. aculeatus remain limited. Many investigations have focused on complex formulations such as Cyclo 3 Fort, which also contains hesperidin methylchalcone and ascorbic acid, making it difficult to attribute the observed effects solely to R. aculeatus. This review provides an overview of the current knowledge on the phytochemistry and pharmacological activities of R. aculeatus. The available data support the plant’s traditional use, yet further well-designed experimental and clinical studies are needed to clarify its mechanisms of action, confirm its therapeutic potential, and ensure safety and standardization in medicinal preparations. Full article

Backgrounds: Non-alcoholic fatty liver disease (NAFLD) is a multifaceted metabolic disorder that has become a prominent public health problem worldwide. As a traditional Chinese medicine formula, the ErChen decoction (ECD) possesses significant effects on metabolic syndrome. Methods: To determine whether ECD can relieve lipid accumulation and insulin resistance (IR) in liver cells, NAFLD and IR cell models were established by treating HepG2 cells with free fatty acids and an overdose of insulin, respectively. Bioinformatics and experimental evidence demonstrated that ECD could ameliorate NAFLD by modulating multiple pathways. The optimal combination of the key compounds in ECD was identified by the orthogonal experiment. Results: For lipid homeostasis, ECD suppressed de novo lipogenesis and reduced the cholesterol level by activating the AMPK signaling pathway. Concurrently, ECD enhanced hepatic β-oxidation by inducing PPARα-mediated upregulation of ACOX-1 and CPT-1α. ECD also resolved hepatic insulin resistance by activating the IRS1-Akt-FoxO1 pathway. The combined treatment with 100 μM liquiritin (LQ), 200 μM glycyrrhizic acid (GA) and 200 μM hesperidin (HEN) exhibited the best effect in reducing TG content in NAFLD model cells. Conclusions: ECD exhibited superior activities in activating the AMPK signaling pathway compared to the optimal compound combination. The comparison between the ECD and its key compounds demonstrated the superior synergistic effects of the herbs in ECD. Full article

Phytochemicals are plant-derived bioactive compounds with antioxidant, anti-inflammatory, and epigenetic modulatory effects that may contribute to the prevention and management of chronic diseases. This review synthesizes recent evidence on the molecular mechanisms through which phytochemicals influence oxidative stress, inflammatory signaling, and epigenetic regulation. A targeted literature search of the PubMed and Web of Science databases (2015–2025) identified over 400 experimental and review studies investigating phytochemicals with documented antioxidant and epigenetic activities. Eligible articles were selected based on relevance to oxidative stress, inflammation, and DNA or histone modification pathways in chronic diseases. Data were qualitatively analyzed to highlight mechanistic links between redox balance, transcriptional regulation, and disease modulation. The results indicate that several phytochemicals, including hesperidin, phloretin, lycopene, and silybin, modulate signaling cascades—NF-κB, Nrf2, and PI3K/Akt—while also influencing DNA methylation and histone acetylation to restore gene expression homeostasis. Despite strong in vitro and in vivo evidence, translation to clinical practice remains limited by low bioavailability, lack of standardized formulations, and insufficient human trials. Future research should prioritize integrative study designs linking molecular mechanisms to clinical endpoints. Understanding the epigenetic actions of phytochemicals may guide the development of nutraceutical strategies for chronic disease prevention. Full article

Gummy candies can be improved with some beneficial health properties by adding healthier ingredients such as fruit extracts rich in bioactive compounds. In this study, gummy candies were fortified with orange peel extract at 7.5% (GC7.5) and 15% (GC15), obtained using ultrasonic-assisted extraction. Hesperidin (53.83 and 122.80 µg/g) and narirutin (9.32 and 20.98 µg/g) were found in higher concentration in gummy candies. After in vitro gastrointestinal digestion (GID), the bioaccessibility of hesperidin was 100.3% and 83.4% for GC7.5 and GC15, respectively, while for narirutin it was 99.15% and 80.58% for GC7.5 and GC15, respectively. In reference to antioxidant activity measure with 2,2-diphenyl-1-picrylhydrazyl scavenger assay, the GID increased this capacity by 29.90% and 6.1% for GC7.5 and GC15, respectively, whilst for ferric reducing activity power assay, the GID reduced the antioxidant capacity by 6.46% and 9.97% for GC7.5 and GC15, respectively. With regard to chemical composition, GC7.5 and GC15 reduce the moisture (2.49% and 5.74%) and protein content (5.84% and 10.23%) compared to control. The extract acts as a coloring agent, while the pH and water activity were not affected by orange peel addition in both GC7.5 and GC15. Consequently, these findings suggest that orange peel is a valuable source of bioactive compounds, making it a promising ingredient for developing natural food ingredients with antioxidant benefits. Full article

Citrus fruit processing, mainly for fresh juice production in the food industry, generates significant amounts of residues and by-products enriched with bioactive components. Peels are the primary waste fraction of citrus fruits, along with discarded pulp and seeds. This study aimed to identify the most fast and sustainable extraction process for flavonoids on a laboratory scale by varying the solvent and extraction methodology, and comparing the yields in order to evaluate their influence on total and individual flavonoid content. A chromatographic analysis was also performed using ultrahigh-performance liquid chromatography (UHPLC) with a 10 min run time. Our focus was on selecting the most user-friendly and cost-effective methodology. Ultrasound- and microwave-assisted extraction equipment were used with green solvents (water and ethanol) and compared for their efficiency in recovering flavonoid compounds from a mixture of peel and pulp. For this study, two widely cultivated Mediterranean citrus varieties were selected: ‘Marsh’ seedless grapefruits (Citrus paradisi Macf.) and ‘Comun’ mandarins (C. deliciosa Ten.). Lab-scale extraction results showed that ultrasound-assisted extraction with a simple ultrasonic bath, using an ethanol–water mixture provided the highest total flavonoid recovery and improved the extraction of key flavanones such as hesperidin, narirutin, and naringin. All ethanol–water mixtures tested (1:1, 7:3, and 3:7) yielded higher flavonoid levels in grapefruit (approximately 2500 mg/100 g DW) and mandarin (approximately 1200 mg/100 g DW) wastes compared with water or ethanol alone. This method offers a scalable and green strategy for valorizing citrus residues. Full article

The endothelium, once considered merely a vascular lining responsible for selective permeability to water and electrolytes, is now recognised as a key regulator of vascular tone through the release of mediators such as oxylipins, nitric oxide, and hyperpolarizing factors. This in vitro study investigated the biological activity of Vesvein, a natural formulation containing Diosmin/Hesperidin, Ruscus aculeatus, Bromelain, and Ananas comosus, on intestinal and endothelial cells. Vesvein enhanced intestinal cell viability and preserved barrier integrity, as demonstrated by increased tight junction expression at both single and double concentrations. In endothelial cells, the compound improved parameters linked to venous insufficiency, elevating nitric oxide production by approximately 1.39-fold at a single dose and 1.65-fold at a double dose. These findings indicate a potential role for Vesvein in supporting endothelial health and vascular function in vitro. Preliminary evidence from intestinal models further suggests preserved barrier properties, which may positively influence absorption and bioavailability, thereby enhancing its vascular benefits. Full article

Atherosclerosis (AS) currently lacks fully effective treatments. This study investigated the natural compound hesperidin as a potential therapy. Apolipoprotein E knockout (ApoE^−/−) mice were used as a model of atherosclerosis; we found that hesperidin treatment improved physiological and metabolic health, reduced plaque formation, and decreased systemic inflammation and oxidative stress. Hesperidin also reshaped gut microbiota, increasing beneficial bacteria (Verrucomicrobia and Bacteroidota) and significantly lowering fecal levels of branched-chain amino acids (BCAAs: valine, leucine, and isoleucine) by 27.4%, 50.1%, and 40.8%, respectively. These changes were linked to specific microbial shifts. We conclude that hesperidin alleviates atherosclerosis likely by modulating the gut microbiota–BCAA–host axis, identifying it as a promising dietary intervention or therapeutic agent. Full article

Genetic truncation or mutation of the gene encoding band 4.1, ezrin, radixin, and moesin (FERM) domain protein containing 4A (FRMD4A) is associated with brain developmental diseases, including microcephaly with global developmental delay. It has also been identified as a risk factor for Alzheimer’s disease. By analogy with other FERM domain-containing proteins, FRMD4A is believed to regulate cell morphogenesis and/or cell polarization in central nervous system (CNS) cells; however, it remains unclear whether and how dysfunction of FRMD4A and/or its closely homologous protein FRMD4B causes abnormal morphogenesis in neuronal cells. Here, we describe for the first time the roles of FRMD4A and FRMD4B in process elongation in neuronal cells. Knockdown of Frmd4a or Frmd4b using specific RNA-targeting clustered regularly interspaced short palindromic repeat (CRISPR) and Cas13-fitted gRNAs led to decreased process elongation in primary cortical neurons. Similar decreases in neuronal marker expression were observed in the N1E-115 cell line, a model of neuronal differentiation. Furthermore, hesperetin, an aglycone of the citrus flavonoid hesperidin known to promote neuroprotective signaling, recovered the decreased process elongation induced by the knockdown of Frmd4a or Frm4b. Hesperetin also stimulated phosphorylation of mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPKs/ERKs), which could help promote neuronal processes. These results suggest that FRMD4A and FRMD4B regulate process elongation through a possible signaling pathway linked to the sustained phosphorylation of MAPKs/ERKs. Crucially, this study reveals that, at the molecular and cellular levels, hesperetin can restore normal phenotypes when FRMD4A protein or FRMD4B protein is impaired. Full article

Background/Objectives: The Centaurea genus is characterized by many species, a broad biological diversity, and a rich secondary metabolite content. These species exhibit various biological activities, including antioxidant, anti-inflammatory, antimicrobial, antiproliferative, and wound-healing properties. However, there are limited anticancer research studies available on the species. This study aims to investigate the potential cytotoxic effects of dichloromethane (CRD) and methanol (CRM) extracts obtained from the root of the endemic Centaurea lycaonica to clarify the mechanism of apoptosis by the intrinsic pathway on the human endometrial cancer cell line RL95-2 based on phytochemical analysis. Methods: The cytotoxicity studies were performed using a Real-Time Cell Analyzer (xCELLigence) and the MTT assay. The activities of caspase 3, caspase 9, Bax, and Bcl-2 were evaluated to investigate the molecular mechanism of apoptosis. LC-HRMS determined the phytochemical content of extracts. Results: CRD and CRM had a concentration-dependent effect in increasing caspase 3 and 9 activities and Bax/Bcl-2 ratios compared to the control with low IC₅₀ values. Conclusions: Apoptosis induction was more pronounced with CRM, which was enriched in hesperidin; this association warrants targeted validation with purified standards. Full article

The objective of this study was to evaluate the antiviral activity of glucosyl hesperidin (GH), a water-soluble derivative of hesperidin with known antioxidant and anti-inflammatory properties, in order to explore its potential applications. Antiviral activity was assessed using feline calicivirus (FCV), a surrogate model for human norovirus, a major foodborne pathogen. Cytotoxicity testing in Crandell–Rees feline kidney (CRFK) cells demonstrated that GH exhibited high biocompatibility, maintaining 100% cell viability at concentrations up to 8000 μM. Antiviral efficacy assays revealed that GH inhibited FCV replication in a concentration-dependent manner across the range of 250~8000 μM, with a half-maximal inhibitory concentration (IC₅₀) of 3281 μM. Complete viral inhibition, however, was not achieved at the maximum concentration tested. In conclusion, GH was shown to inhibit FCV while maintaining low cytotoxicity, indicating its potential as a natural, water-soluble candidate for the suppression of norovirus. Full article

Dried orange pulp (Citrus sinensis) is known for its antioxidant properties. This study aimed to examine the effects of adding dried orange pulp (OP) to the layers’ diets on the concentration of selected elements in the egg. The present work was part of a bigger project aiming to investigate the effect of orange pulp in layers’ diets on the performance of birds and egg quality. There were three dietary treatments and 63 layers per treatment, with 189 layers in total. Cages were the experimental units, and seven cages were allocated per treatment (n = 7). The dietary treatments were (1) a control treatment (C) that involved a basal diet without orange pulp addition, (2) an OP treatment with the addition of 9% dried orange pulp, and (3) a hesperidin–naringin (EN) treatment with 0.767 g hesperidin and 0.002 g naringin added per kg of diet; these levels of hesperidin and naringin represent those present in dried orange pulp for the OP treatment. Birds were fed the diets for 30 days. The diets had similar energy and protein levels and contained the same vitamin and mineral premixes. The analyzed egg (yolk, albumen, shell) elemental profile consisted of As, Ca, Cd, Co, Cr, Cu, Fe, Mg, Mn, Ni, Sb, Se, Sr, V, and Zn and was determined via Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Dried orange pulp supplementation significantly altered the elemental profile. OP largely altered the element concentrations in albumen and egg yolk. Most notably, it decreased the concentrations of Co (p < 0.001), Fe (p < 0.001), Mn (p < 0.001), Ni (p = 0.046), and Se (p = 0.035) in egg yolk and those of Co (p = 0.011), Fe (p = 0.025), Cr (p = 0.049), Cu (p = 0.001), and Se (p = 0.014) in albumen. In addition, it decreased the concentrations of As (p = 0.025) and Ca (p = 0.025) in the eggshell. Principal component analysis was applied to the concentrations of the examined elements in all egg parts to explore the relationships between the elements and detect those capable of distinguishing samples, resulting in the apparent separation of yolk, albumen, and eggshell samples. Further analysis revealed that all samples were clustered into the three dietary treatments, resulting in 100% correct classification. The chelating and antioxidant capacities of flavonoids are intricate and rely on a variety of factors. OP supplementation modulated the deposition of specific elements in egg parts in comparison to those from layers fed a typical diet. Thus, this study indicated that eggs with specialized elemental profiles could be created. Full article

Advanced glycation end-products (AGEs) are associated with the dysfunction of proximal tubular epithelial (PTE) cells in lifestyle diseases. Urinary stones induce cytotoxicity in PTE cells, and various medicines have been developed to mitigate or prevent their generation/accumulation. The leaves of Quercus salicina Blume/Q. stenophylla Makino—used in Japanese folk medicine—contain quercetin, hesperidin, and p-hydroxycinnamic (p-coumaric) acid, which can suppress the cytotoxicity of intra-/extracellular AGEs. This review investigated the effects of quercetin, hesperidin, and p-coumaric acid on PTE cells in terms of their metabolism following oral administration and the associated organs and bacteria. Current evidence indicates that, in PTE cells, non-metabolized quercetin and p-coumaric acid may suppress intra-/extracellular AGE-induced cytotoxicity, whereas the metabolites of quercetin and hesperidin may inhibit the generation of AGEs. However, little is known of the effects of p-coumaric acid metabolites. Quercetin, hesperidin, and p-coumaric acid may collectively suppress the cytotoxicity of intra-/extracellular AGEs in PTE cells. This review on the current paradigm of Q. salicina/Q. stenophylla extract provides a useful baseline for the design of further preclinical and clinical investigations. Full article

Hesperidin (HD) is predominantly found in citrus fruits, and has been shown to possess various biological properties, such as anti-inflammatory, antioxidant, and anti-carcinogenic. However, its application is limited by poor solubility. In this study, a new solid dispersion (SD) of hesperidin was prepared by ball milling using PVPK30 as the carrier, and the in vitro and in vivo studies and the therapeutic effects about colitis in rats were evaluated. In vitro analysis revealed that the solid dispersion showed a better release effect. The cumulative release of HD-SD reached 48.24% at 120 min, which was 5.9 times that of pure HD. In vivo studies demonstrated that C_max and AUC_0–24 were significantly higher in HD-SD compared with pure HD (p < 0.01), which were 2.67 and 1.50 times that of HD, respectively. Furthermore, treatment with HD-SD significantly alleviates symptoms and histological features in acetic acid (AA)-induced colitis in rats. Furthermore, HD-SD treatment significantly ameliorated the disease severity of acetic acid (AA)-induced colitis in rats, as evidenced by improved clinical signs, attenuated histological damage, and decreased levels of inflammatory factors (TNF-α, IL-6, and IL-1β). Moreover, the structure and relative abundance of the gut microbiota were modulated. Specifically, the relative abundance of Erysipelotrichaceae was decreased and the relative abundance of Bacteroidota, Lachnospiraceae, and [Eubacterium]_coprostanoligenes_group were increased. These results suggest that HD-SD could serve as a gut-health-promoting functional ingredient, potentially contributing to the dietary management of colitis through microbiota modulation. Full article

Eucomis autumnalis is a bulbous ornamental species with ethnobotanical relevance. In vitro cultures offer a sustainable tool for biomass propagation and metabolite production. This study investigates the effects of nine LED light spectra: red (R), blue (B), red–blue (RB), RB with green (RBG), yellow (RBY), far-red (RBfR), ultraviolet (RBUV), white (WLED), and fluorescent light (Fl, control), on the morphogenesis, polyphenol production, and antioxidant potential of E. autumnalis shoot cultures. Cultures were maintained on MS medium with 5 µM BA and 0.5 µM NAA. HPLC-DAD analysis identified 11 phenolic acids and 4 flavonoids, including eucomic acid, characteristic of the genus. Light quality impacted compound-specific accumulation and antioxidant activity, with responses varying among compounds and treatments. R and B light increased catechin, gentisic acid and hesperidin (289, 195, 245 mg/100 g DW), while UV suppressed flavonoids by ca. 2-fold for catechin and flavanones compared to other lights. RBG and RBfR induced the highest eucomic acid accumulation (424 mg/100 g DW), ferulic acid and epicatechin, correlating strongly with ABTS•+ activity (18–19% higher than other lights; r > 0.6–0.8). These findings highlight LED spectral modulation as a tool to enhance the phytochemical quality of E. autumnalis in vitro and provide a foundation for future biotechnological applications. Full article

The growing prevalence of mental health issues and cognitive impairment poses a significant challenge to global public health. Conditions such as depression, anxiety, neurodegenerative diseases, and stress-related cognitive dysfunction are becoming more common, while conventional pharmacotherapies are often limited by suboptimal efficacy, adverse side effects, and concerns about long-term use. Against this backdrop, neurophytochemistry—the study of plant-derived bioactive compounds—has emerged as a promising area of research. This review explores the potential of selected phytochemicals to support mental well-being and cognitive function via various molecular mechanisms. Compounds such as apigenin, hesperidin, and epigallocatechin gallate have been shown to have a significant impact on key regulatory pathways. These include enhancing neurogenesis via brain-derived neurotrophic factor, modulating neurotransmitter systems (such as GABA and serotonin), and attenuating oxidative stress and neuroinflammation. The therapeutic relevance of these compounds is discussed in the context of depression, anxiety, Alzheimer’s disease, Parkinson’s disease, and stress-related cognitive dysfunction, often referred to as ‘brain fog’. This review synthesizes evidence published between 2010 and 2025 from several scientific databases, including PubMed, Scopus, Web of Science, and Embase. Preliminary evidence from in vitro studies and animal models indicates that neurophytochemicals could enhance synaptic plasticity, protect neurons from oxidative damage, and modulate inflammatory pathways, particularly those involving NF-κB and the Nrf2/ARE antioxidant response. In addition, early human clinical trials have shown that phytochemical supplementation can lead to improvements in mood regulation, stress response, and cognitive performance. Furthermore, emerging evidence suggests that the gut–brain axis plays a key role in mediating the effects of phytochemicals. Several compounds have been found to modulate the composition of gut microbiota in ways that could enhance the function of the central nervous system. While the initial results are encouraging, more high-quality clinical trials and mechanistic studies are required to validate these findings, optimize dosage regimens, and guarantee the safety and efficacy of long-term use. Thus, neurophytochemicals represent a promising integrative approach to alleviating the increasing burden of mental and cognitive disorders through naturally derived therapeutic strategies. Full article