Search Results (831)

Randia echinocarpa is an endemic shrub species of Mexico, commonly known as papache in the state of Sinaloa, where it has traditionally been used in medicinal practices. The present study evaluated the phenolic profile and antioxidant capacity of different tissues (leaf, bark, and fruit pulp) of R. echinocarpa. Phenolic compounds were characterized using HPLC–PDA–MS, which allowed the identification of seven compounds in the leaf, six in the bark, and six in the fruit pulp. Chlorogenic acid, ellagic acid, and rutin were among the most abundant compounds detected. Total phenolic content varied depending on tissue and season, with the highest concentration observed in leaves during autumn (2.770 ± 0.011 mg GAE g⁻¹) and the lowest in bark during winter (0.437 ± 0.009 mg GAE g⁻¹). This study also reports, for the first time, the concentrations of tannins and flavonoids in R. echinocarpa, with the highest content found in leaves during autumn (0.261 ± 0.003 mg EE g⁻¹ and 2.186 ± 0.005 mg RE g⁻¹, respectively). Antioxidant capacity was evaluated using DPPH and ABTS radical scavenging assays, with leaf extracts showing the highest activity, with IC₅₀ values of 0.82 mg mL⁻¹ and 1.21 mg mL⁻¹, respectively. These results provide new information on the phenolic composition and antioxidant potential of R. echinocarpa, contributing to the phytochemical characterization of this traditionally used medicinal species. Full article

The rising demand for sustainable and circular approaches in the agro-industrial sector has generated interest in repurposing herbal tea residues as sources of high-value bioactive compounds. This work focusses on recovering phytochemicals from Rosa canina L. peel and seed dust (by-products of processing of herbal tea in filter tea bags) using green extraction techniques. Two environmentally friendly technologies were used: ultrasound-assisted extraction (UAE) with a sonotrode and subcritical fluid extraction (SBFE). The extracts were qualitatively profiled using (HR) LC-ESI-QToF-MS/MS and quantified using HPLC-PDA. Both by-products contained phenolic substances, including gallic acid derivatives, ellagic acid, and flavonoids such as quercetin and quercetin-3-O-glucoside (only in the peel). Additionally, Folin–Ciocalteu’s assay was used to determine Total Phenolic content (TP). The extraction efficiency was considered in terms of phenolic compound recovery and total phenolic content obtained under the respective experimental conditions. The maximum TP for SBFE was reported in samples extracted with ethanol–water (48:52) at 180 °C, producing 3876.67 GAE mg/L for peel and 1648.57 GAE mg/L for seeds. In the UAE, extraction with ethanol–water (48:52) for 10 min yielded the maximum TP of 2773.81 GAE mg/L for peel and 957.86 GAE mg/L for seeds. These findings highlight the potential of R. canina infusion by-products as long-term sources of bioactive compounds for use in nutraceutical, cosmetic, and pharmaceutical industries. Full article

‘Mollar de Elche’ pomegranate is highly valued for its sweet flavor but faces significant commercial hurdles due to pale coloration and sensitivity to postharvest disorders. This study investigates the impact of preharvest foliar applications of L-α-amino acids, applied alone (AA) or combined with 2.5% sorbitol (Sor–AA), on secondary metabolism and physiological resilience, defined here as the fruit’s capacity to maintain metabolic homeostasis and stabilize antioxidant pigments during cold storage (7 °C). Our results show that both treatments triggered a substantial shift in secondary metabolism, doubling anthocyanin concentrations at harvest and effectively overcoming the cultivar’s color deficit. While the AA treatment maximized fruit quantity per tree, the Sor–AA combination achieved the highest total yield (83.58 ± 6.82 kg) and individual fruit weight (469.00 ± 16.00 g) through a ‘metabolic bypass’ that optimizes energy use. Crucially, the physiological resilience of the fruit was uniquely bolstered by the Sor–AA treatment, which was the only strategy to stabilize anthocyanin levels (~108 mg L⁻¹) and maximize free ellagic acid in the husk (371.72 mg kg⁻¹) throughout 42 days of storage. Multivariate PCA (explaining 79.79% of variance) confirmed that the synergy of amino acids and sorbitol triggers systemic metabolic reprogramming. Consequently, this targeted agronomic approach could provide significant economic benefits by increasing the proportion of export-grade fruit and extending the commercial window for the pomegranate sector. Full article

Skin aging is driven by intrinsic factors, such as the accumulation of reactive oxygen species, and extrinsic factors, including ultraviolet (UV) radiation, which accelerate oxidative stress and extracellular matrix degradation. Strategies to mitigate skin aging often focus on antioxidant and anticollagenase activities. Several studies have shown that Pomegranate (Punica granatum L.) peel is an underutilized by-product rich in ellagitannins, which can be hydrolyzed into ellagic acid, a compound with well-documented bioactivity. Therefore, this study aims to investigate the effect of microbial fermentation using Lactiplantibacillus plantarum and Saccharomyces cerevisiae on the physicochemical properties and bioactivity of pomegranate peel juice. Non-fermented juice (NFJ), L. plantarum-fermented juice (LFJ), and S. cerevisiae-fermented juice (SFJ) were used for comparative evaluation. The results showed that fermentation (LFJ and SFJ) led to decreased pH and sugar content, along with significant increases in ellagic acid concentration, antioxidant activity, and collagenase inhibition compared to NFJ. After 168 h, ellagic acid levels increased to 329.87 µg/mL in LFJ and 341.41 µg/mL in SFJ, compared to 263.86 µg/mL in NFJ. Antioxidant activity also increased to 73.82%, 83.25%, and 82.70% for NFJ, LFJ, and SFJ, respectively. Meanwhile, collagenase inhibition was 67.43%, 71.81%, and 73.66% for NFJ, LFJ, and SFJ, respectively. These results provide scientific evidence that microbial fermentation enhances the bioactivity of pomegranate peel juice, showing its potential as a sustainable source of natural ingredients for future cosmetic applications. Further studies on formulation, stability, and safety are needed to translate the results into practical skincare products. Full article

Cholangiocarcinoma (CCA) is a rare malignancy of the biliary tree with increasing global incidence and mortality and limited therapeutic options. Intrahepatic cholangiocarcinoma (iCCA) metabolism exhibits enhanced glycolysis, oxidative phosphorylation, and glutamine utilization. In this study, we investigated the therapeutic potential of targeting glutaminolysis in iCCA, identifying glutamate dehydrogenase (GDH)—which converts glutamate to α-ketoglutarate—as a key metabolic hub. We evaluated the effects of pomegranate waste extract (PWE), a by-product of industrial pomegranate juice production, on cell viability, proliferation, migration, ATP production, and extracellular acidification in CCLP1 cells, an established iCCA model. Our results are consistent with an altered cellular energy metabolism. We further assessed GDH enzymatic activity, expression, and transcriptional regulation in the presence or absence of PWE and its major components, punicalagin and ellagic acid. GDH expression was downregulated by PWE in a dose-dependent manner through inhibition of NF-κB signaling, revealing a new mechanistic link between NF-κB and GDH. In addition, GDH enzymatic activity was dose-dependently inhibited by PWE, as well as punicalagin and ellagic acid. Notably, punicalagin was identified as a novel competitive inhibitor of GDH. Overall, these findings provide the first evidence that modulation of glutaminolysis through GDH targeting impairs iCCA cell growth and metabolism, supporting GDH as a promising metabolic target. This study highlights pomegranate-derived compounds as potential leads for the development of adjunctive or preventive strategies in intrahepatic cholangiocarcinoma. Full article

Pecan nutshells (PNS), once considered agricultural waste, are now recognized as a sustainable source of natural antioxidants with potential therapeutic benefits against oxidative stress-related diseases. This narrative review synthesized evidence from the last decade, including predominantly in vitro and in vivo studies, with limited clinical evidence. PNS are particularly rich in polyphenols (gallic acid, ellagic acid, vanillic acid, catechins), with phenolic and flavonoid concentrations reported to be 5–20 times higher than those in the edible kernels. Their antioxidant actions involve free radical scavenging, metal chelation, enhancement of enzymatic defenses, and modulation of redox signalling. Preclinical findings suggest protective roles in cardiovascular disease, diabetes, neurodegeneration, and cancer, mediated through reduced lipid peroxidation, improved glucose metabolism, neuroprotection, and anticarcinogenic activity. However, variability in extraction methods, cultivar differences, and bioavailability issues remain major challenges. Standardized clinical studies are needed to validate the therapeutic potential of PNS as a sustainable antioxidant source. Full article

The escalating global burden of Ulcerative Colitis (UC) underscores the urgent need for novel therapeutic strategies. Although dietary modulation is known to influence UC progression, the specific molecular mediators remain largely undefined. Recently, the G protein coupled receptor 35 (GPR35) has emerged as a promising target for maintaining gut homeostasis and promoting intestinal epithelium repair. Yet, whether the therapeutic benefits of dietary polyphenols are mediated through the direct activation of GPR35 remains unexplored. Here, the NanoLuc Binary Technology (NanoBiT) assay was first used to identify the potential GPR35 agonist from a library of 30 natural polyphenolic compounds. We discovered Ellagic acid (EA), a natural polyphenol abundant in fruits and nuts, as the potent GPR35 agonist owing to its most potent agonistic effect. The dose-dependent effect was further confirmed by both NanoBiT and Bret assay. Then, the binding site of the ligand-receptor complex was predicted via molecular docking, and key interactions were validated by site-directed mutagenesis. The results indicated the key binding site of the complex was Gln93, Arg100, Arg151, Phe163 and Ser262. And the conformation of the complex was verified stable by the molecular dynamics simulation. The bioactivity of EA was then evaluated in vivo. And the in vivo experiment indicated that EA alleviated the symptoms of UC. In addition, complementary in vitro assays, including a wound healing (scratch) assay and an SRB proliferation assay, were employed to investigate its effect on intestinal epithelial repair. The in vitro experiment demonstrated that EA enhanced the migration and proliferation of human colonic epithelial cells, an effect that was specifically abolished by the GPR35 antagonist CID2745687, indicating the key role GPR35 played in the intestinal repair. Collectively, our study demonstrates that the natural polyphenolic compound EA promotes epithelial healing and ameliorates colitis by acting as a GPR35 agonist. Full article

This study presents a comprehensive analysis of the bromatological profile of fruits from rowanberry (Sorbus aucuparia L.) and hawthorn (Crataegus monogyna Jacq.), as well as the polyphenol bioaccessibility under in vitro simulated gastrointestinal conditions, antioxidant activity and the inhibition of lipid peroxidation in a biological model (egg yolk). The fruits were demonstrated to be rich in bioactive compounds, containing comparable total vitamin E levels (~65 mg/kg), with α-tocopherol as the predominant isomer, and measurable amounts of xanthophylls, mainly lutein (20.19–21.69 μg/g), astaxanthin, and canthaxanthin. HPLC-DAD analysis identified 19 polyphenolic compounds, with catechin being the dominant compound in rowanberry fruits (4.36 mg/g), while epigallocatechin and catechin were the most abundant in hawthorn fruits. In vitro gastrointestinal digestion showed elevated intestinal bioaccessibility of hydroxybenzoic acids, with ellagic acid reaching ~96% in the intestinal phase of rowanberry fruits and ~109% in hawthorn fruits, indicating increased availability. In hawthorn fruits, flavanols exhibited greater stability and higher bioaccessibility, with catechin reaching 101% in the gastric phase, epicatechin remaining highly bioaccessible (98–97%), and epigallocatechin showing moderate bioaccessibility (24–50%). Both fruit extracts exhibited antioxidant activity, with hawthorn fruits showing significantly higher ABTS and DPPH scavenging capacities. Rowanberry and hawthorn fruits exhibited an inhibitory effect on lipid peroxidation in yolk homogenates, reducing malondialdehyde formation to 37.19 mg/kg and 20.58 mg/kg from 50.79 mg/kg, respectively, although their efficacy remained lower than that of synthetic antioxidants. The findings of this study indicate that rowanberry and hawthorn fruits are promising sources of bioactive compounds, exhibiting significant antioxidant activity in biological models and supporting the potential valorization of these underutilized fruits for functional food and nutraceutical applications. Full article

The carob tree (Ceratonia siliqua L.) is indigenous to the Mediterranean basin, noted for its adaptability to biotic and abiotic stresses and its long history of use in traditional agroforestry systems. This review critically analyzes the phytochemical composition of carob, its traditional medicinal uses, and its contemporary applications in the cosmetic, pharmaceutical, and agri-food sectors. Particular attention is placed on the valorization of carob pods, seeds, and leaves, which are transformed into high-value products, including locust bean gum and polyphenol-rich extracts. Recent studies indicate that carob is a rich source of bioactive compounds, particularly phenolic acids and flavonoids such as gallic acid, chlorogenic acid, ellagic acid, catechins, quercetin, and luteolin. These compounds have primarily been investigated in vitro and in vivo, where they exhibited antioxidant, antimicrobial, and potential cardioprotective and gastrointestinal-related effects. This chemical diversity underscores their potential as a prime substitute for future nutraceutical and pharmaceutical applications. The review further addresses the ecological and socio-economic relevance of carob cultivation, particularly in countries such as Algeria, where reforestation and agro-industrial valorization remain underexploited despite their significant economic potential. Overall, this work highlights the need for a comprehensive and critical evaluation of carob-derived bioactive compounds and encourages further well-designed studies, especially clinical investigations, to better substantiate their health-related benefits while supporting sustainable use of this multipurpose species. Full article

Background: Punica granatum L. (pomegranate) is a medicinal plant traditionally used for its antimicrobial and antioxidant effects. Recent evidence supports its expanding applications in dermatology and dermocosmetics. Purpose: This systematic review aimed to evaluate the skin-related biological activities of pomegranate extracts, identify the key bioactive compounds involved, and elucidate the underlying molecular mechanisms relevant to skin health and aging. Methods: A total of 732 studies were screened using AIReviewer clustering. Fifty-four original articles were selected on the basis of inclusion criteria prioritizing molecular evidence, in vitro and in vivo assays, and clinical relevance. Results: Pomegranate extracts exhibit a broad range of dermocosmetic properties, including antioxidant, anti-inflammatory, antibacterial, wound healing, moisturizing, photoprotective, and collagen-preserving effects. These effects are primarily attributed to ellagitannins (punicalagin and punicalin), ellagic and gallic acid, triterpenoids (oleanolic, maslinic, and asiatic acids), flavonoids (quercetin and catechins), anthocyanins, and fatty acids (punicic acid). Pomegranate extracts modulate oxidative stress by scavenging reactive oxygen species and upregulating Nrf2-mediated antioxidant pathways. They inhibit matrix metalloproteinases (MMP-1 and MMP-3), suppress proinflammatory cytokines (TNF-α and IL-6), and stimulate fibroblast proliferation, extracellular matrix remodeling, and hyaluronic acid synthesis. Their photoprotective activity provides enhanced UVB resistance and higher SPF values. Recent advances in fermentation and nanotechnology have been shown to increase the bioavailability and stability of compounds found in pomegranate, offering new formulation strategies. Conclusions: Pomegranates are a promising source of multifunctional phytochemicals with validated dermocosmetic applications. Their incorporation into advanced delivery systems may increase their therapeutic potential for skin protection, regeneration, and antiaging interventions. Full article

This study investigated the protective effects and underlying mechanisms of ellagic acid (EA) against high-fat diet (HFD)-induced obesity. Using network pharmacology, STAT3 and AKT1 were identified as pivotal regulatory targets. In vivo experiments demonstrated that EA intervention significantly reduced body weight inducement, improved lipid profiles, and attenuated intestinal oxidative stress and inflammation in HFD-fed rats. Furthermore, EA restored intestinal architecture and mitochondrial morphology. Mechanistically, EA markedly downregulated the expression of PPARG, STAT3 and p-AKT1 in both intestinal tissues and TNF-α-stimulated HaCaT cells. Collectively, these findings suggest that EA prevents HFD-induced obesity by alleviating intestinal oxidative stress and mitochondrial dysfunction through the modulation of the PPARG/STAT3/p-AKT1 signaling axis. This study provides novel evidence for EA as a potential natural bioactive compound for the management of metabolic disorders. Full article

Hyperlipidemia is a major global risk factor for cardiovascular disease, underscoring the need for safe, multi-target preventive strategies. In this study, two novel dietary supplements were developed by blending freeze-dried aqueous extracts of chamomile (CDS) or thyme (TDS) with linseed oil (1:1, w/w) and evaluated for their phytochemical composition, antioxidant capacity, and hypolipidemic efficacy. Total phenolics, total flavonoids, fatty acid composition, volatile constituents, and individual phenolic profiles were characterized, while antioxidant activity was assessed using DPPH· radical-scavenging and FRAP assays. Hypolipidemic activity was investigated in a Triton X-100-induced hyperlipidemia rat model through an assessment of plasma lipid parameters, oxidative stress and inflammatory markers, and liver and kidney function indices, supported by hepatic histopathology. Molecular docking was performed to explore the interactions of major bioactive compounds with AMP-activated protein kinase (AMPK) and HMG-CoA reductase. Both CDS and TDS exhibited strong antioxidant activity and high polyphenol content, with kaempferol and chlorogenic acid identified as the predominant phenolics in CDS and TDS, respectively. β-Farnesene and carvacrol were the main volatile constituents. In vivo, both formulations significantly reduced total cholesterol, triglycerides, LDL-C, lipid peroxidation markers, and TNF-α, while increasing HDL-C and improving cardiac risk indices, with more pronounced effects observed for TDS. Histopathological analyses confirmed marked hepatoprotection, particularly in the TDS-treated group. Docking analyses identified ellagic acid as the strongest dual binder to both AMPK and HMG-CoA reductase. Overall, these findings demonstrate that chamomile-linseed and thyme-linseed formulations exert synergistic, multi-target antioxidant and hypolipidemic effects, supporting their potential as nutraceutical strategies for the early prevention and management of hyperlipidemia and cardiometabolic risk. Full article

Fluoride-induced osteoarthritis (F-OA) is a debilitating manifestation of endemic fluorosis, with limited preventive or therapeutic strategies. Rosa roxburghii juice (RRJ), a traditional medicinal/edible product, has shown protective effects against skeletal fluorosis, yet its active constituents and molecular mechanisms are not fully understood. In this study, an integrated strategy combining bioinformatics analysis, network pharmacology, molecular docking and dynamics simulations, limited proteolysis–mass spectrometry (LiP–MS), and in vitro experiments was employed to systematically elucidate the protective mechanisms of RRJ against F-OA. Forty-four core F-OA-associated genes were identified, with TP53 and the p53 signaling pathway emerging as central regulatory hubs. Quercetin, Epicatechin, Emodin, and Ellagic acid were screened as key bioactive components of RRJ and demonstrated strong binding affinity toward core targets, including TP53. Cellular experiments showed that these compounds significantly attenuated sodium fluoride-induced cellular injury. LiP–MS analysis further revealed widespread protein conformational remodeling following treatment, with TP53 exhibiting pronounced structural sensitivity. Mechanistically, these active compounds mitigated fluoride-induced pathological changes by suppressing p53 mRNA expression and restoring proteasome-mediated p53 degradation. This study provides systematic pharmacological evidence supporting Rosa roxburghii fruit as a promising functional food for the prevention and management of skeletal fluorosis and F-OA. Full article

Multiple sclerosis (MS) is characterized by progressive mitochondrial dysfunction affecting complexes I, III, and IV of the electron transport chain, contributing to axonal energy failure and neurodegeneration. This review examines the potential of combining β-hydroxybutyrate (βHB), epigallocatechin-3-gallate (EGCG), and ellagic acid (EA) as a multi-target therapeutic strategy to restore mitochondrial function in patients with MS. Experimental and clinical studies demonstrate that each compound exerts complementary mechanisms. Ketone bodies provide an alternative energy substrate and restore complex I activity via sirtuin-dependent pathways. EGCG acts predominantly at the peripheral level by reducing systemic inflammation and oxidative stress. EA-derived urolithins effectively cross the blood–brain barrier to directly enhance mitochondrial biogenesis and respiratory chain function in the central nervous system. Clinical trials have reported improvements in fatigue, cognition, mood, and muscle function following supplementation with these compounds. The convergence of their actions on energy restoration, reactive oxygen species reduction, and epigenetic modulation of protective pathways suggests their synergistic potential. Optimized delivery strategies, including exogenous ketone salts, liposomal EGCG, and microencapsulated EA, may overcome bioavailability limitations and interindividual variability in the gut microbiota metabolism. Full article

Psidium cattleyanum Sabine (strawberry guava, araçá) is an ethnomedicinal plant with reputed health benefits; however, its potential for treating skin disorders remains underexplored. This study aimed to characterize the phytochemical profile of P. cattleyanum leaves from Cabo Verde and evaluate their bioactivity relevant to skin health. Phytochemical analysis was performed using high-performance liquid chromatography-mass spectrometry (LC-MS) and spectrophotometric assays. Key biological activities were assessed in vitro, including antioxidant capacity (free radical scavenging assays), anti-aging enzyme inhibition (collagenase, elastase, and tyrosinase), and antibacterial activity against skin pathogens (agar diffusion, minimum inhibitory concentration, and combination studies with standard antibiotics). Cytotoxicity was evaluated using Vero cells (MTT assay). Additionally, a topical cream containing the leaf extract was formulated and subjected to physicochemical stability and sensory testing. LC-MS revealed a rich polyphenolic composition in the leaf extract, including abundant phenolic acids (gallic and ellagic acid derivatives) and flavonoid glycosides. The extract exhibited a high total phenolic content and strong antioxidant activity in DPPH/ABTS assays. It showed potent inhibition of collagenase, elastase, and tyrosinase, indicating an anti-aging effect against wrinkle formation and hyperpigmentation. The extract also demonstrated broad antimicrobial efficacy against skin-associated bacteria, such as Staphylococcus aureus and Cutibacterium acnes, with no antagonism and partial synergism observed when combined with certain antibiotics. The P. cattleyanum extract was successfully incorporated into a cream formulation that remained physically and chemically stable (no phase separation, consistent droplet size, and pH) over 90 days, with good homogeneity and acceptable sensory characteristics (neutral odor, smooth texture, and good spreadability). P. cattleyanum leaves from Cabo Verde are a rich source of bioactive compounds with multifunctional dermatological benefits. This study demonstrates that the P. cattleyanum leaf extract exhibits significant antioxidant, antimicrobial, and anti-aging activities in vitro, supporting its potential use as a natural ingredient for skin care. Full article