Search Results (59)

The rapid expansion of the global nutraceutical industry has heightened the urgency for rigorous yet efficient safety assessment of food-derived bioactives. Conventional toxicological methods, while indispensable, are often costly, time-consuming, and insufficient to keep pace with the rapid product innovation in this sector. In this context, in silico models for predicting Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET), alongside broader computational toxicology tools, are increasingly recognized as scalable and cost-effective strategies for early-stage safety evaluation of nutraceuticals. Techniques such as quantitative structure–activity relationship (QSAR) modeling, molecular docking, and physiologically based pharmacokinetic (PBPK) simulation enable early prioritization of candidate compounds, forecasting of potential enzyme- or receptor-mediated interactions, and prediction of bioactive metabolite profiles, prior to costly experimental or clinical evaluation. Yet, their application in the nutraceutical domain presents unique challenges. Food matrices are chemically complex, bioactive data remain sparse and unevenly curated, and long-term, low-dose effects are difficult to capture with existing computational frameworks. These limitations constrain predictive accuracy and raise questions about general applicability across diverse classes of compounds. Therefore, this review critically examines both the opportunities and limitations of computational safety assessment for nutraceuticals. It synthesizes representative case studies, evaluates current methodological limitations, and discusses the evolving regulatory landscape alongside emerging integrative frameworks such as New Approach Methodologies (NAMs) that may guide the future of nutraceutical safety assessment. Full article

The demand for sustainable nutrients and bioactive compounds has increased interest in underutilized wild plants. Forestiera tomentosa, a Mexican drupe-bearing species, is largely unexplored. This study evaluated the proximate composition, physicochemical and functional properties, phenolic profile, antioxidant capacity, and toxicological safety of F. tomentosa fruit. The fruit showed high carbohydrate content [71.94% dry weight (DW)], with notable crude fiber (7.90% DW), protein (7.39% DW), and lipid (4.30% DW) contents. Analysis revealed a mildly acidic pH (5.66), titratable acidity of 0.32%, and total soluble solids of 2.33 °Brix. The fruit powder had a low water activity (0.42) and a favorable water solubility index (56.10%), oil absorption (4.54%), and foaming capacity (19.71%). The fruit contained high levels of soluble phenols (280.42 mg GAE/g DW), flavonoids (98.89 mg CE/g DW), anthocyanins (54.53 mg C3G/g DW), and condensed tannins (94.05 mg CE/g DW). High-performance liquid chromatography identified 20 phenolic compounds, with 3-(4-hydroxyphenyl) propionic acid, syringic acid, catechin, epicatechin, and gallocatechin being predominant. The fruit showed significant radical scavenging and reducing potential (DPPH, ABTS, and FRAP). Toxicological evaluation using the Artemia salina bioassay showed a 100% survival rate across all concentrations, indicating no acute toxicity. In silico ADMET predictions revealed favorable pharmacokinetic properties, including high intestinal absorption and compliance with Lipinski’s rule of five. These findings position F. tomentosa as a promising, non-toxic source of functional ingredients for the food, nutraceutical, and pharmaceutical industries, supporting biodiversity conservation and sustainable resource utilization. Further studies are needed to evaluate the potential health benefits of this fruit in vitro and in vivo. Full article

Argan tree (Argania spinosa L. Skeels), an endemic Moroccan species, is widely recognized for its traditional medicinal and nutritional uses. It has long been employed to promote skin and cardiovascular health, regulate blood glucose levels, and support overall wellbeing. Traditionally, different parts of the argan tree, including argan oil, leaves, and other plant-derived preparations, have been used to manage various health conditions such as diabetes, gastritis, gastric ulcers, rheumatism, joint and muscle pain, skin disorders including acne, eczema, and inflammation, as well as wound healing and dental problems. This narrative critical review compiles and evaluates current knowledge on the ethnobotany, phytochemistry, pharmacology, and toxicology of argan tree to support its evidence-based application. Relevant literature was collected from major English and French scientific databases, focusing on studies addressing the plant and its principal bioactive constituents. Ethnobotanical data indicate the extensive use of argan oil, leaves, and other plant parts in traditional remedies and dietary practices. Phytochemical investigations reveal a rich composition dominated by unsaturated fatty acids, tocopherols, phytosterols, and polyphenolic compounds. Experimental studies highlight a broad spectrum of biological activities, including antioxidant, antidiabetic, antibacterial, and anti-obesity effects, along with emerging applications in nanotechnology. Toxicological findings generally suggest low toxicity and good safety profiles under tested conditions. Overall, A. spinosa exhibits substantial ethnopharmacological relevance and diverse bioactivities, supporting its continued exploration for nutraceutical and therapeutic applications. Full article

Prickly pear (Opuntia ficus-indica (L.) Mill.) generates substantial agro-industrial by-products, such as press cake, seed, and oil, that remain underexploited despite their recognized phytochemical richness. This study reports the systematic optimization, characterization, and bioactivity profiling of flavonoid-rich extracts recovered from these three matrices. A Box–Behnken design (BBD) coupled with response surface methodology (RSM) was applied to optimize the ultrasound-assisted extraction (UAE) of total flavonoid content (TFC) from press cake using a natural deep eutectic solvent (NADES: fructose–glycerol–sorbitol–water and FGSH), selected through an initial screening of fifteen solvent systems. The quadratic polynomial model showed excellent fit (R² = 0.9852; R²adj = 0.9687; MAPE = 1.31%; Durbin–Watson = 1.857), and optimal extraction conditions were established at 37.6 min extraction time, 35.6% ultrasonic power, and 29.4 °C, yielding a maximum predicted TFC of 54.78 ± 0.49 mg quercetin equivalents (QE)/mL. HPLC-DAD analysis of the press cake extract revealed five isorhamnetin derivatives as the dominant flavonoids, with isorhamnetin-3-O-glucoside (23.18 ± 0.12 mg/g DW) and isorhamnetin-3-O-rutinoside (13.80 ± 0.28 mg/g DW) as the most abundant. Comprehensive bioactivity assessment demonstrated significant antioxidant capacities (CUPRAC: 191.35 ± 3.22 µM AAE; ORAC: 184.44 ± 3.44 µM TE; DPPH: 103.47 ± 9.98 µM TE for press cake extract), potent in cellulo ROS/RNS suppression in a yeast UV-stress model (85.9 ± 1.0% inhibition for press cake), and differential tyrosinase inhibition across fractions (press cake: 32.8%; seed: 57.5%; oil: 83.8%), highlighting the oil as a potent anti-melanogenic ingredient. In silico safety prediction (ProTox-II/pkCSM) confirmed the favorable toxicity profiles of all identified isorhamnetin derivatives (LD₅₀ > 5000 mg/kg; Toxicity Class V). These results collectively position Opuntia ficus-indica by-products as high-value natural sources of bioactive flavonoids with applications in cosmetic, nutraceutical, and dermatological formulations. Full article

Geisha coffee (Coffea arabica L. cv. Geisha) is internationally recognized for its exceptional sensory quality; however, its functional properties and bioactive composition remain insufficiently explored. This study evaluated the phytochemical profile, antioxidant capacity, vascular bioactivity, and toxicological safety of an aqueous extract of roasted Geisha coffee (AErGC) from the Chiriquí highlands, Panama. The chemical composition was determined using HPLC-PDA. Antioxidant activity was assessed using DPPH, ABTS, and lipid peroxidation assays. Vascular effects were studied in rat aortic rings, and safety was evaluated through Artemia salina and a single-dose acute oral toxicity model in rats (OECD 423). Chemical characterization was performed by HPLC-PDA, revealing notably elevated levels of caffeine (69.5 ± 6.4 mg/g) and 5-O-caffeoylquinic acid (74.5 ± 6.9 mg/g). The extract exhibited strong free radical scavenging capacity, with an IC₅₀ value of 14.7 ± 4.9 µg/mL in the DPPH assay, and inhibited lipid peroxidation by 72.71 ± 1.63% at 15.6 µg/mL. In endothelium-intact rings, AErGC induced a concentration-dependent vasorelaxant effect, reaching a maximum relaxation of 70.84 ± 2.9%. Toxicological results showed an LC₅₀ > 1000 µg/mL in A. salina and an oral LD₅₀ > 2000 mg/kg, classifying the extract as Category 5 (low toxicity). These findings highlight Panamanian Geisha coffee as a promising functional beverage with antioxidant and vascular protective properties, supporting its potential as a nutraceutical. Full article

This study investigates the valorization of Nephelium lappaceum (rambutan) shell, an agro-industrial byproduct, as a sustainable source of bioactive compounds through comprehensive chemical and functional characterization. Phytochemical profiles were determined using spectrophotometrics and HPLC-DAD-MS/MS, revealing a composition dominated by ellagitannins (e.g., geraniin, corilagin, chebulagic acid) and ellagic acid derivatives, alongside significant levels of total phenolics (25,982.2 mg/100 g DW) and anthocyanins. The extract exhibited strong antioxidant activity (DPPH IC₅₀ = 8.02 μg/mL; TEAC = 5703.92 μmol TE/g), consistent with its high phenolic content. Biological evaluation demonstrated antimicrobial activity against a broad panel of Gram-positive and Gram-negative bacteria, including multidrug-resistant strains, with greater efficacy against Gram-positive species (Staphylococcus aureus, MIC = 2.5 mg/mL). The extract also showed significant antibiofilm activity, achieving up to 93% inhibition. Antitumoral assays revealed selective cytotoxicity, particularly against HeLa cells (IC₅₀ = 260 μg/mL; TI = 11.5), indicating preferential effects on tumor over non-tumor cells. Importantly, hemolytic assays confirmed low toxicity, with negligible erythrocyte membrane disruption across tested concentrations. Overall, these findings highlight rambutan shell as a rich source of phenolic bioactives with multifunctional biological properties and favorable safety profile, supporting its potential application in nutraceutical and pharmaceutical formulations within a circular economy framework. This study aligns with SDG 3 and SDG 9 by promoting the valorization of agro-industrial waste as a source of safe bioactive compounds for health-related applications. Full article

This study examines 36 wild Asteraceae species that are traditionally used as food in Sicily and Bulgaria, highlighting their ethnobotanical, nutritional, and pharmacological relevance. Some taxa, such as Cichorium intybus, Silybum marianum, Artemisia vulgaris, Taraxacum officinale, and Tussilago farfara, are integral to the Mediterranean and Balkan diets, enhancing nutrition through their fiber, minerals, and bioactive compounds. This ethnobotanical survey revealed a clear geographic pattern in species usage: 13 species were found to be consumed solely in Bulgaria, 18 solely in Sicily, and five species in both regions. The distribution highlights the existence of shared culinary traditions that have been distinctly adapted to the unique ecological conditions present in each locale. The main metabolite classes identified include flavonoids, phenolic acids, lignans, and sesquiterpene lactones, all of which are associated with antioxidant, anti-inflammatory, hypolipidemic, and anticancer properties. Specific taxa within the investigated group were found to contain alkaloids that warrant toxicological attention. Some species within the studied group contain alkaloids that may pose toxicity risks. T. farfara is known to accumulate pyrrolizidine alkaloids, which are associated with liver damage and potential genotoxic effects, highlighting the importance of thorough toxicological evaluations before recommending these plants for consumption. This study also demonstrates how common culinary processes, such as boiling and blanching, significantly impact the concentration, stability, and safety profile of these bioactive compounds. Overall, the research supports the promotion of wild Asteraceae species as valuable and sustainable nutritional and nutraceutical resources. This approach aligns with efforts to preserve biodiversity and maintain traditional Mediterranean and Balkan food practices, integrating both ecological and cultural sustainability. Full article

Natural bioactive peptides have emerged as pivotal candidates in modern science due to their multifaceted biological activities and versatile applications across biomedicine, biotechnology, and nutraceuticals. These molecules exhibit a broad pharmacological spectrum including antimicrobial, antiplatelet, antioxidant, antihypertensive, and antitumor properties, positioning them as potent therapeutic agents and essential functional food constituents. Compared to synthetic alternatives, their inherent structural diversity, biocompatibility, and biodegradability offer a superior safety profile by minimizing systemic toxicity and adverse effects. This review provides a comprehensive analysis of the primary natural reservoirs of these peptides, which encompass terrestrial flora and fauna as well as marine organisms and microorganisms, while elucidating their complex mechanisms of action and structure–function relationships. Furthermore, we evaluate contemporary methodologies for peptide identification and optimization, such as high-throughput proteomics, computational modeling, and strategic chemical modifications aimed at enhancing metabolic stability and bioavailability. Although bottlenecks in extraction, scalable production, and proteolytic susceptibility persist, recent breakthroughs in recombinant technology and rational design are facilitating their industrial translation. Finally, we discuss future perspectives focused on the synergy between artificial intelligence, nanotechnology, and sustainable circular economy strategies to maximize the therapeutic accessibility and functional efficacy of natural peptides. Full article

The European chestnut (Castanea sativa Mill.) industry generates substantial amounts of underutilized biomass, including shells, leaves, and spiny burs. Distinguishing itself from existing literature, this review presents a novel, integrated life-science analysis that redefines these by-products as a complementary ‘bioactive triad’, ranging from metabolic regulators to anti-virulence agents, rather than interchangeable sources of polyphenols. Although traditionally discarded, these by-products are rich sources of polyphenols, ellagitannins, and flavonoids, with promising potential for nutraceutical, cosmetic, and pharmaceutical applications. This review examines recent advances in the valorization of chestnut by-products, focusing on extraction strategies, chemical profiles, and biological activities. Shell valorization has increasingly shifted toward green extraction technologies, such as subcritical water extraction and deep eutectic solvents, which strongly influence bioactive recovery and composition. Chestnut leaves emerge as a sustainable resource enriched in hydrolysable tannins with anti-inflammatory and quorum sensing-inhibitory properties, particularly relevant for dermatological applications. Spiny burs, often the most phenolic-rich fraction, display marked antioxidant activity and the ability to potentiate conventional antibiotics against pathogens such as Helicobacter pylori. Despite these promising features, major challenges remain, including cultivar-dependent chemical variability, the predominance of in vitro evidence, and safety concerns related to the accumulation of potentially toxic elements. Overall, while chestnut by-products represent valuable resources within circular bioeconomy frameworks, their successful industrial and practical translation will require standardized extraction protocols, robust bioavailability assessments, and well-designed in vivo and clinical studies to ensure safety and efficacy. Full article

Silk Lutein (SL), a novel protein-bound lutein complex derived from Bombyx mori cocoons, offers an intriguing alternative to traditional sources. This study aimed to establish the complete toxicological profile of SL. Evaluations of the acute oral toxicity of SL (LD₅₀ > 2000 mg/kg body weight (BW)) were conducted in female Wistar rats and ICR mice. In the chronic toxicity trial, male and female Wistar rats were administered daily oral dosages of SL (5, 25, 50 mg/kg BW) for a duration of six months. The results indicated a robust safety profile for SL, with no treatment-related adverse effects detected. Apart from demonstrating its foundational safety, this study found that prolonged SL administration possessed significant, beneficial bioactive properties. Following four months of treatment, both male and female Wistar rats administered SL exhibited a significant hypotensive effect, maintaining their systolic blood pressure at approximately 120 mmHg and thereby averting the age-related hypertension observed in control subjects. Additionally, SL significantly reduced serum triglyceride levels in both sexes. The findings of this study confirm SL’s potential as a multipurpose nutraceutical by demonstrating that it is a safe constituent with a favorable toxicological profile and notable cardiovascular effects. Full article

Microalgae are increasingly recognized as valuable dietary supplements due to their rich nutritional composition and the presence of bioactive metabolites with antioxidant, antitumor, and metabolism-modulating activities. This study evaluated the nutraceutical potential of a methanolic extract of Scenedesmus sp. using an integrated in vitro, in vivo, and metabolomic approach. The extract exhibited selective cytotoxicity against L5178Y-R murine lymphoma cells while showing low toxicity toward human peripheral blood mononuclear cells, indicating a favorable safety and selectivity profile. Additionally, it demonstrated moderate antioxidant activity, a significant antihemolytic effect, and no hemolytic activity even at high concentrations, supporting its hematological safety. In vivo assays showed that oral administration of doses up to 1000 mg/kg was well tolerated, with no adverse effects on body weight or hepatic biochemical markers. Treated animals displayed improved systemic antioxidant responses and enhanced glucose tolerance. Metabolomic analysis revealed a profile enriched in essential amino acids, osmolytes, organic acids, and bioactive metabolites such as β-hydroxybutyrate and betaine, compounds associated with metabolic regulation, redox balance, and epigenetic modulation. Overall, these findings highlight Scenedesmus sp. as a promising nutraceutical source with potential application as a complementary strategy for cancer prevention or treatment. Full article

Moringa oleifera has been recognized for its adaptability, nutritional richness, and multipurpose potential, particularly in resource-limited regions. While most research has focused on its leaves, moringa seeds remain underutilized despite their broad applicability in the environmental, agricultural, and food sectors. This review systematically and critically examines recent scientific literature on the use of M. oleifera seeds across these fields, emphasizing their functional value, applications, and challenges for sustainable use. The review follows the SALSA methodology (Search, Appraisal, Synthesis, and Analysis), a structured and iterative framework designed to identify, evaluate, and integrate scientific evidence from diverse sources. The analysis encompasses three main areas: (i) water treatment, where moringa seed extracts have achieved turbidity removal efficiencies above 90% and effective adsorption of dyes and potentially toxic elements; (ii) agriculture, where seed-derived fertilizers improve soil fertility, nutrient availability, and crop yield compared to conventional inputs; and (iii) the food industry, where moringa seed derivatives enhance the nutritional, functional, and antioxidant properties of bakery, beverage, and oil-based products. Overall, M. oleifera seeds emerge as a versatile and sustainable resource with proven potential as a natural coagulant, biofertilizer, and nutraceutical ingredient. By integrating findings from both English and Spanish language studies, this work highlights their contribution to sustainable water management, agricultural productivity, and food innovation, while emphasizing the need for further safety evaluation and process optimization to support large-scale application. Full article

Turmeric (Curcuma longa L., Zingiberaceae) is a widely consumed spice and functional food valued for its bioactive constituents. Using an activity-guided strategy, this study identified the dichloromethane fraction as the most potent anti-inflammatory fraction, exhibiting markedly stronger inhibition of reactive oxygen species (ROS) production than ibuprofen (IC₅₀ $\le$ 0.4 vs. 11.2 μg/mL). Bioassay-guided purification yielded bisacurone (1), didemethoxycurcumin (2), and β-turmerone (3), with compounds 1 and 2 reported here for the first time in this fraction. Among them, β-turmerone displayed the strongest anti-inflammatory activity (IC₅₀ = 4.7 μg/mL), consistent with in silico docking and molecular dynamics analyses, revealing greater binding affinity and complex stability with myeloperoxidase (ΔG_bind = −20.90 vs. −18.89 kcal/mol for ibuprofen). Gas chromatography–mass spectrometry (GC-MS) profiling revealed a phytochemical profile dominated by turmerones and curlone, correlating with the observed bioactivity. None of the fractions exhibited acute toxicity in brine shrimp lethality assays, indicating a favorable preliminary safety profile. Our findings demonstrate the value of activity-guided isolation combined with computational validation for identifying turmeric-derived bioactives with promising nutraceutical potential, warranting further in vivo evaluation. Full article

Berberine hydrochloride, a bioactive isoquinoline alkaloid with metabolic, lipid-lowering, and antimicrobial properties, is increasingly synthesized for nutraceutical applications due to its high yield and, therefore, cost-effectiveness. However, synthetic production can raise significant safety concerns, particularly regarding potentially toxic residuals generated during chemical process. A primary concern is the formation of nitrosamines, a class of genotoxic impurities associated with the use of secondary amines, nitrites, and strong acids in synthetic processes. This article examines the reported synthetic routes for berberine hydrochloride, with emphasis on the use of toxic reagents and intermediates that, if not completely consumed or effectively removed during synthesis process, may persist as impurities in the final product. In contrast, berberine obtained with aqueous botanical extraction avoids such hazardous synthetic precursors and retains co-occurring alkaloids, offering a cleaner safety profile and potential synergistic benefits. Full article

Bacterial vaginosis (BV) is a highly prevalent vaginal infection characterized by a dysbiotic shift in the vaginal microbiota, with Gardnerella vaginalis acting as a principal pathogen. Despite its association with adverse reproductive outcomes, BV remains underexplored from both mechanistic and therapeutic standpoints. Standard antibiotic regimens frequently fail due to high recurrence rates driven by multidrug-resistant (MDR) G. vaginalis strains and biofilm formation. In response, natural compounds and nutraceuticals, owing to their intrinsic antibacterial, antibiofilm, and immunomodulatory properties, have emerged as promising candidates for alternative BV therapies. In this paper, we first compile and critically evaluate preclinical and clinical evidence on the efficacy of plant extracts, essential oils (EOs), probiotics, vitamins, proteins, fatty acids, and enzymes against G. vaginalis, emphasizing their mechanistic insights in restoring vaginal microbial balance. Next, we focus on the integration of these bioactive agents into engineered nanosystems, such as lipid-based nanoparticles (LNPs), polymeric carriers, and inorganic nanostructures, to overcome limitations related to solubility, stability, and targeted delivery. Nonetheless, comparative studies, combination therapies, and recent patent developments are discussed to highlight how naturally derived molecules can enhance antimicrobial potency and reduce cytotoxicity. In conclusion, these platforms demonstrate superior in vitro and in vivo efficacy, offering a paradigm shift in the management of BV. Key challenges include scalable manufacturing, regulatory approval, and comprehensive safety assessment. Future research should prioritize standardized nanoparticle (NP) synthesis, detailed pharmacokinetic and toxicity profiling, and well-designed clinical trials to validate nature-inspired, nanoengineered therapies against G. vaginalis-induced BV. Full article