Search Results (306)

Background: Nigella sativa L. is a medicinal plant widely recognized for its diverse pharmacological properties. This study aimed to evaluate the antioxidant, diuretic, and cytotoxic effects of an aqueous seed extract and its effects on selected biochemical parameters in rats. The pharmacokinetic potential of identified bioactive compounds was also investigated in silico. Methods: The aqueous extract was prepared by maceration. Antioxidant activity was assessed using DPPH, reducing power, and total antioxidant capacity (TAC) assays. We evaluated the diuretic effect in vivo in Wistar rats by measuring urinary concentrations of Na⁺, K⁺, Cl⁻, and creatinine, using furosemide as a reference drug. Cytotoxicity was assessed in splenocytes and thymocytes. We analyzed seven identified compounds in silico for physicochemical properties, Lipinski compliance, intestinal absorption, cytochrome P₄₅₀ inhibition, and blood–brain barrier permeability. Results: The extract showed significant antioxidant activity, with a DPPH IC₅₀ of 0.254 ± 0.002 mg/mL and a TAC of 125.01 ± 4.220 mg AAE/g. It significantly increased urinary electrolyte and urinary concentration, indicating a diuretic effect lower than that of furosemide. Plasma analyses showed decreased electrolyte concentrations and increased creatinine levels. Cell viability exceeded 90%, indicating no significant cytotoxicity. Most compounds complied with Lipinski’s rule of five and showed favorable predicted intestinal absorption, with limited cytochrome P₄₅₀ inhibition. Several compounds were predicted to cross the blood–brain barrier. Conclusions: The aqueous extract of N. sativa demonstrated antioxidant and diuretic activities without significant cytotoxicity. These findings support its pharmacological potential and warrant further investigation of its mechanisms of action and therapeutic relevance. Full article

Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a dose-limiting complication of paclitaxel (PTX) therapy, for which effective treatments are still lacking. This study evaluated the neuroprotective potential of Thymoquinone (TQ), a bioactive derivative of Nigella sativa, in mitigating chronic PTX-induced neurotoxicity without compromising antineoplastic activity. We first performed in vitro experiments using Sprague–Dawley rat embryonic (E15) Dorsal Root Ganglia (DRG) (Envigo Laboratory (Udine, Italy)) to assess neurotoxicity through neurite outgrowth evaluation. To investigate the molecular mechanisms underlying TQ’s putative neuroprotective mechanisms, SIRT1 protein expression was additionally evaluated by western blot, while MCF-7 and MDA-MB-231 breast cancer cells were used to monitor cytotoxicity via MTT assay. We then moved to in vivo experiments, in which chronic neuropathy was induced in rats using PTX (10 mg/kg, i.v., weekly for 4 weeks). TQ was co-administered orally (5–10 mg/kg/day). The effects of TQ on peripheral neuropathy were assessed through behavioral testing, neurophysiological assessments, and histological analysis of Intraepidermal Nerve Fibre density (IENF), DRG and peripheral nerves. In vitro, TQ (5 μM) significantly attenuated PTX-induced neurite shortening at 24 h; TQ co-treatment fully prevented PTX-induced SIRT1 downregulation in embryonic DRG neurons and did not compromise PTX cytotoxicity in MCF-7 cells, while significantly potentiating it in MDA-MB-231 triple-negative breast cancer cells. In vivo results demonstrated that PTX-treated animals exhibited mild erythroid myelosuppression at the end of treatment. Regarding efficacy, TQ consistently prevented PTX-induced mechanical allodynia throughout the treatment period, and TQ (10 mg/kg) transiently mitigated IENF depletion at mid-treatment; however, no improvement in neurophysiological parameters or peripheral nerve morphology was observed at either time point. Collectively, these findings suggest that, under conditions of chronic PTX exposure, TQ exerts a predominantly analgesic effect in vivo, without conferring meaningful structural neuroprotection against PTX-induced peripheral nerve degeneration. Full article

Evaluating the in vivo systemic tolerance of phytogenic feed additives is a crucial prerequisite before their widespread application in vulnerable newborn ruminants. This study aimed to investigate the systemic effects of orally administered cold-pressed Nigella sativa oil on the hematological and biochemical profiles of neonatal lambs (0–45 days of age) fed exclusively on colostrum and maternal milk. The pre-specified primary endpoint was the absence of clinically meaningful change in hepatorenal markers and complete blood count between groups over 45 days. Thirty-two single-born Merino lambs were divided into a treatment group that received 1.5 mL/day of the oil for the first 15 days of life and an untreated control group. Blood samples were collected on days 0, 7, 21, and 45 to evaluate both immediate and carry-over physiological effects. Using a covariate-adjusted linear mixed-effects model to account for baseline variances, the results demonstrated that the oil was physiologically well-tolerated. The supplementation exerted no significant adverse effects (p > 0.05) on hepatorenal markers or the measured acute-phase protein. The supplementation maintained neonatal energy metabolism stability without inducing artificial lipid suppression in serum triglycerides or total cholesterol levels. Furthermore, the oil preserved hematological homeostasis without negatively impacting red blood cell indices and modulated platelet distribution width indices without causing pathological thrombocytosis. In conclusion, the early direct oral administration of N. sativa oil is a physiologically well-tolerated supplement that supports basal metabolic and hematological stability in pre-ruminant lambs without inducing systemic disruptions within the parameters measured. Full article

Background: Precision nutrition and nutrigenomics have emerged as promising strategies to personalize dietary interventions according to individual genetic, metabolic, and molecular characteristics. However, the potential of nutrigenomic-guided nutraceutical interventions to modulate biological aging pathways remains poorly characterized. Objective: This study aimed to map and synthesize the available evidence from human studies evaluating personalized nutraceutical interventions based on nutrigenomic approaches and their effects on biomarkers associated with biological aging. Methods: A scoping review was conducted following the Joanna Briggs Institute methodology and PRISMA-ScR guidelines. PubMed/MEDLINE, Embase, Scopus, and Web of Science were searched for studies published between 2021 and 2026. Eligible studies included adults aged ≥18 years receiving personalized nutraceutical interventions informed by genetic, genomic, metabolomic, or other molecular data. Outcomes included biomarkers of cellular aging, inflammation, oxidative stress, immunometabolism, and related pathways. Results: Twenty-one studies were included. Interventions involved omega-3 fatty acids, polyphenols, Nigella sativa, vitamin D, methyl-donor micronutrients, fermented papaya preparation, and other nutraceutical preparations and functional food-based interventions. Four major themes emerged: multi-omic stratification approaches, biological aging biomarkers, redox-inflammatory modulation, and applications in metabolic disorders. Most studies demonstrated favorable effects on intermediate molecular biomarkers, including inflammatory cytokines, oxidative stress markers, lipid metabolism, endothelial function, and DNA methylation signatures. However, evidence directly demonstrating slowing of biological aging through validated biomarkers such as epigenetic clocks or telomere dynamics remains limited. Conclusions: Personalized nutraceutical interventions exhibit biological plausibility for modulating pathways associated with healthy aging. Nevertheless, robust longitudinal studies incorporating validated biomarkers of biological aging and clinically meaningful outcomes are needed before their widespread implementation in precision medicine. Full article

Background/Objective: Mature oral biofilms resist conventional antiseptics via dense extracellular polymeric substance (EPS) matrices. Consequently, the prolonged use of broad-spectrum agents like chlorhexidine (CHX) raises profound ecological concerns. Using a mature oral microcosm biofilm model, we evaluated the multifaceted efficacy of 0.5% black cumin seed oil (BCSO) in disrupting structural biomass, suppressing aciduric bacterial viability, and attenuating porphyrin-associated anaerobic biofilm maturation. Methods: Saliva-derived microcosm biofilms were cultivated on hydroxyapatite discs in a mucin-containing medium (0.5% sucrose) for 6 days. Mature biofilms were treated daily for 1 min for 6 days (n = 19/group) with 0.5% BCSO, 0.12% CHX (positive control), or 0.5% dimethyl sulfoxide (negative control). EPS and bacterial biovolumes were quantified using confocal microscopy. Viability was strictly evaluated as aciduric bacterial colony-forming units. Pathogenic potential was specifically assessed as porphyrin-associated maturation by the red-to-green fluorescence intensity ratio (${\mathrm{Ratio}}_{\mathrm{R}/\mathrm{G}}$) using quantitative light-induced fluorescence-digital technology. Results: Compared with the negative control, 0.5% BCSO significantly degraded the EPS matrix (p < 0.001) and bacterial biovolumes (p = 0.045), and reduced aciduric bacterial counts (p = 0.028). Importantly, 0.5% BCSO significantly reduced the ${\mathrm{Ratio}}_{\mathrm{R}/\mathrm{G}}$ (p = 0.015), compared with the negative control, indicating severely attenuated porphyrin-associated anaerobic maturation. In the CHX group, the reduction did not reach statistical significance compared with the negative control (p = 0.399). Conclusions: In vitro, 0.5% BCSO and 0.12% CHX effectively reduced structural biomass and aciduric bacterial viability. Furthermore, BCSO significantly reduced late-stage, porphyrin-associated anaerobic maturation compared with the negative control, whereas the reduction observed with CHX did not reach statistical significance. These findings highlight the potential of BCSO as a targeted natural antibiofilm adjunct, warranting rigorous in vivo and mechanistic validation before clinical translation. Full article

Edible Natural Deep Eutectic Solvents (NADES) offer a route to ready-to-use extracts without solvent removal. This study examined how rational formulation design influences physicochemical properties, extraction performance, energy efficiency, thermal behavior, and cytocompatibility during bioactive recovery from Nigella sativa seeds. Twelve formulations spanning malic acid–polyol, citric acid–polyol, binary polyol, and ternary acid–polyol families were evaluated under standardized ultrasound-assisted conditions and compared with ethanolic ultrasound-assisted extraction, Soxhlet extraction, and cold-pressed oils. Selected NADES formulations outperformed the conventional systems. E1 (malic acid:glycerol:water) achieved the highest total phenolic content and lowest specific energy consumption (40.00 kJ mg⁻¹ GAE), below the Soxhlet benchmark (55.17 kJ mg⁻¹ GAE), whereas E9 (glycerol:xylitol:water) exhibited the greatest ABTS activity. Neat-NADES apparent pH and viscosity were inversely associated with total phenolic content, while viscosity and density were inversely associated with ABTS activity. ATR-FTIR showed stable, solvent-dominated fingerprints over 15 days, whereas DSC better differentiated neat NADES from their extracts. Most systems remained cytocompatible at 10,000× dilution, while acid–polyol formulations reduced viability at 500×; partial neutralization of N5/E5 restored viability. NADES performance was formulation- and application-dependent, requiring joint optimization of composition, acidity, viscosity, energy efficiency, and biologically compatible concentration. Full article

Type 2 diabetes mellitus (T2DM) is increasingly managed through lifestyle measures, yet the value of pairing structured exercise with a well-characterised phytotherapeutic adjunct remains poorly defined. We examined whether adding Nigella sativa (NS) to combined aerobic and resistance exercise (EX) yields greater improvements in metabolic, inflammatory, and oxidative-stress markers than exercise alone in men with T2DM. In this three-arm randomised controlled trial, 90 sedentary, non-smoking men (aged 40–60 years; T2DM duration > 2 years; glycated haemoglobin (HbA1c) 6.5–9.0%; body mass index (BMI) < 30 kg/m²) were allocated 1:1:1 to control, EX, or EX + NS (2 g/day; n = 30 per group) for four weeks. Fasting blood samples obtained before and after the intervention were used to measure glycaemic indices (fasting blood glucose (FBG) and fructosamine), a lipid panel (total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c)), inflammatory markers (tumour necrosis factor-α (TNF-α), interleukin-4 (IL-4), and adiponectin), and oxidative-stress markers (thiobarbituric acid–reactive substances (TBARS) and catalase activity). Outcomes were analysed by two-way repeated-measures analysis of variance (time × group), with partial eta-squared (η_p²) and 95% confidence intervals (CIs) reported for all principal effects. Relative to control, both exercise arms significantly improved body composition and glycaemic, lipid, inflammatory, and oxidative-stress profiles (all p < 0.05). The time × group interaction was significant for every outcome except systolic and diastolic blood pressure and triglycerides. Compared with EX alone, EX + NS produced significantly greater improvements in FBG, HDL-C, TBARS, and catalase activity; changes in fructosamine, total cholesterol, TNF-α, IL-4, and adiponectin favoured EX + NS directionally but did not reach significance after correction for multiple comparisons. Triglycerides, LDL-C, and blood pressure did not differ between the two exercise arms. These hypothesis-generating findings support NS as a candidate adjunct to structured exercise for selected metabolic and redox outcomes, and warrant larger, longer, sex-balanced confirmation. Full article

Defined natural products are often framed as intrinsically safer multi-target alternatives to selective drugs, but this assumption is not pharmacologically justified. This critical review evaluates product-specific adjunctive evidence in respiratory allergy, inflammatory bowel disease, type 2 diabetes, depression, and insomnia. MEDLINE/PubMed records published from 2020 to 23 June 2026 were prioritized, while earlier pivotal randomized trials and quantitative safety studies were retained. Evidence was gated by product identity, human exposure, exposure-compatible target engagement, incremental efficacy, and safety boundaries. Nigella sativa oil improved Asthma Control Test scores by 1.5 points over placebo after 4 weeks, although the clinical importance is uncertain and FEV1 was not significantly improved. Curcumin plus mesalamine induced remission in mild-to-moderate ulcerative colitis (53.8% versus 0%), whereas indigo naturalis produced strong response rates but is constrained by pulmonary arterial hypertension. Berberine improves glycemic surrogates but lacks cardiovascular or renal outcome evidence and shows commercial potency variability. Saffron has a short-term antidepressant signal, while St John’s wort combines extract-dependent efficacy with CYP3A4/P-glycoprotein induction. Overall, selected defined natural products may merit narrow adjunctive roles, but undefined mixtures should not be treated as mechanistically established interventions without batch-level characterization, human pharmacokinetics, objective endpoints, and prospective interaction surveillance. Full article

Black cumin (Nigella sativa L.) oil is one of the most important vegetable oils with food, therapeutic and medicinal uses; however, it has high acid and peroxide values even in fresh oil extracted by cold pressing. One of the main factors that can cause high peroxide value (PV) and acid value (AV) in the extracted black cumin oil (BO) is the presence of essential oils (EO), which are highly sensitive to oxidation. In this study, separation by steam was used to strip EO from BO, and the obtained oil quality was evaluated during storage in room conditions for 90 days. The AV and PV in BO without EO were lower and showed a lower increase compared to BO with EO during storage. Chlorophyll, carotenoid, thymoquinone, phytosterols and tocopherols were lower in samples without EO than those with EO. Fatty acid composition was similar in both types of oils, but linoleic acid (18:2) was decreased at a higher rate in the oil with EO during storage. Therefore, the obtained results show that steam stripping of EO from BO can be suggested to obtain oil with lower PV and AV and with a relatively longer shelf life. Full article

This study evaluates the effects of four pretreatment methods: convection heating, microwaving, ultrasonication, and pulsed electric fields (i.e., PEF), on the chemical composition, color profile, functional properties, phenolic profile, antioxidant activity, fatty acid composition, and protein content of Nigella sativa L. (i.e., black cumin) cold-pressed cake. Seeds were subjected to each pretreatment prior to cold press extraction. Microwave, ultrasonication, and pulsed electric field pretreatments produced the lowest press cake yields (63.61–65.54%), statistically equivalent to one another. Also, the microwave-treated and control samples retained the highest protein content on a dry matter basis (30.81 and 30.79 g·100 g⁻¹, respectively). Ultrasonication yielded the highest total phenolic and total flavonoid contents. Analysis of the press cake identified salicylic acid and catechin as the predominant bioactive compounds, suggesting potential antimicrobial and antioxidant applications. These findings provide evidence-based guidance for selecting Nigella sativa L. seed pretreatment strategies that at the same time optimize cold press oil extraction and the nutritional, functional, and bioactive value of the residual press cake. Thus, supporting its utilization as a sustainable by-product for food and feed applications. Full article

Black seed (Nigella sativa L., Ranunculaceae) possesses antimicrobial activity due to its bioactive compound, thymoquinone. This study aimed to extract thymoquinone from black seed using an alternative natural deep eutectic solvent (NADES) through an optimization approach. A NADES based on malic acid and choline chloride was employed in this work. The Box–Behnken design was used to investigate the effects of the molar ratio of malic acid to choline chloride, water addition, and ultrasonication time. These variables were varied as follows: the malic acid to choline chloride molar ratio ranged from 2:1 to 4:1, the mass ratio of water to NADES from 0.5:2 to 1.5:2, and the ultrasonication time from 60 to 120 min. The results showed that the malic acid to choline chloride molar ratio, the quadratic term of the malic acid to choline chloride molar ratio, and the quadratic term of ultrasonication time significantly affected thymoquinone extraction. The optimal condition, which yielded the highest thymoquinone concentration, was determined to be a malic acid to choline chloride molar ratio of 4:1, a mass ratio of water to NADES of 1:2, and an ultrasonication time of 60 min. Under these conditions, the thymoquinone concentration was 70.57 ± 5.78 µg/mL, closely aligning with the predicted value. The thymoquinone-rich extract obtained using NADES exhibited antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans. In conclusion, NADES serves as an effective alternative solvent for extracting thymoquinone from black seed. Full article

Background: Drug resistance and treatment-associated toxicity remain major limitations of conventional chemotherapy for triple-negative breast cancer (TNBC). Thymoquinone (TQ), a bioactive phytochemical derived from Nigella sativa, has demonstrated anticancer properties and may enhance the therapeutic efficacy of docetaxel (DTX) through complementary molecular mechanisms. Objective: To investigate whether TQ potentiates the antitumor activity of DTX in MDA-MB-231 TNBC cells by affecting apoptosis, oxidative stress, wound closure, and PI3K/AKT pathway-related gene expression. Methods: MDA-MB-231 TNBC cells and HaCaT keratinocytes were treated with TQ, DTX, or their combination. Cell viability was determined using the MTT assay, and drug interactions were evaluated by the Chou–Talalay combination index (CI) method. Apoptosis, intracellular reactive oxygen species (ROS) production, ROS rescue experiments using N-acetyl-L-cysteine (NAC), caspase-9 expression, wound closure, and gene-expression changes were assessed using Annexin V/PI flow cytometry, DCFH-DA-based flow cytometric and fluorescence analyses, immunocytochemistry, wound-healing assay, and quantitative real-time PCR (qRT-PCR), respectively. Bioinformatic analyses were performed to identify signaling pathways associated with the observed molecular alterations. Results: The TQ + DTX combination demonstrated synergistic cytotoxicity and significantly increased apoptotic cell death compared with either monotherapy. Combination treatment markedly enhanced intracellular ROS accumulation, whereas NAC pretreatment significantly attenuated ROS generation and partially reversed the cytotoxic and pro-apoptotic effects, suggesting the involvement of ROS in the observed antitumor effects. Caspase-9 immunoreactivity was markedly increased following combination treatment, suggesting the involvement of the intrinsic apoptotic pathway. Furthermore, the combination significantly suppressed wound closure and downregulated BCL2, PIK3CA, and AKT1 while upregulating BAX, CASP9, and PTEN. Bioinformatic analyses identified apoptosis, p53, PI3K/AKT, mTOR, and MAPK signaling as the principal pathways potentially associated with the observed gene expression changes. Conclusions: TQ potentiates the antitumor activity of DTX, with the involvement of oxidative stress, apoptotic signaling, suppression of wound closure, and regulation of PI3K/AKT pathway-related gene expression in TNBC cells. These findings provide evidence supporting further preclinical investigation of the TQ + DTX combination as a promising therapeutic strategy for triple-negative breast cancer. Full article

Vulvovaginal candidiasis (VVC) is a common mucosal infection that predominantly affects reproductive-aged women. Although conventional antifungal agents remain the primary treatment option, there is growing interest in developing alternative therapeutic approaches that can enhance antifungal efficacy while potentially reducing treatment burden. Natural products have emerged as valuable sources of bioactive compounds with antifungal potential, offering opportunities for novel combination-based therapies. Ebselen (EB), an organoselenium compound with potent redox-modulating and antifungal properties, and its structurally related analogs represent promising candidates for such strategies. Likewise, black seed oil (BSO), derived from Nigella sativa, and its major active constituent, thymoquinone (TQ), have demonstrated antifungal activity against Candida species, supporting their investigation as natural product-based partners in synergistic antifungal combinations. Commercially prepared BSO and purified TQ were tested across a range of concentrations in a broth microdilution assay in combination with EB and novel organoselenium analogs, including Ebselen Oxide (EB-Ox) and N-octyl-1,2-benzisoselenazol-3(2H)-one (APM C6). Minimum inhibitory concentrations (MICs) for single agents and combinations were determined, and the resulting datasets were analyzed using the web-based Synergy Finder platform. EB, EB-Ox, and APM C6 showed consistent synergy with BSO and TQ against C. albicans (clinical isolate S1), as indicated by positive synergy scores relative to monotherapies. Full article

Introduction: Oil pulling therapy has gained increasing attention as a natural oral hygiene practice; however, evidence regarding its clinical effectiveness remains limited and inconclusive. This study aimed to evaluate the effects of oil pulling therapy on dental plaque regrowth and tooth discoloration compared with chlorhexidine. Materials and Methods: One hundred systemically healthy dental students were randomly allocated to five groups: chlorhexidine, coconut oil, black cumin seed oil, terebinth oil, and distilled water. Following professional prophylaxis, participants refrained from mechanical oral hygiene for four days and used their assigned intervention twice daily. Plaque accumulation was assessed using the Turesky modification of the Quigley–Hein Plaque Index, gingival inflammation using the Gingival Index, and tooth color using CIELAB color difference measurements. Data were analyzed using one-way ANOVA or Kruskal–Wallis test with appropriate post hoc tests, depending on the distribution of data. Results: Plaque scores differed significantly among groups (p < 0.001), with chlorhexidine showing superior plaque inhibition compared with all oil-based interventions and distilled water. Gingival index values were lowest in the chlorhexidine group, although differences among oil groups were not statistically significant. Tooth discoloration was significantly greater with chlorhexidine than with all oil-based interventions (p < 0.001). Conclusions: Oil pulling therapies demonstrated lower anti-plaque efficacy than chlorhexidine but resulted in less tooth discoloration. These findings suggest that oil pulling may serve as an adjunct rather than an alternative to conventional plaque control. Full article

Objective: Lung cancer (LC) remains a leading cause of cancer mortality worldwide. Thymoquinone (TQ), a bioactive compound derived from Nigella sativa, possesses anti-inflammatory and antioxidant properties, but its precise mechanisms concerning miRNA regulation in LC are poorly defined. This study investigates the anti-cancer potential of TQ through modulation of microRNA signaling in LC. Methods: We employed an integrated approach combining bioinformatic predictions with rigorous experimental validation in A549 lung adenocarcinoma cells and SHP-77 human small-cell lung carcinoma (SCLC) cells. Bioinformatic analyses predicted miRNA targets, and experimental techniques included dual-luciferase reporter assays, miRNA inhibition, TaqMan RT-qPCR, cell-based ELISA, and Western blotting to dissect the molecular pathway. Results: We identified the transcription factor BACH1 as a direct and novel target of hsa-miR-155-5p. TQ potently suppressed interferon-γ-induced expression of both hsa-miR-155-5p and its target, BACH1. This TQ-mediated suppression led to subsequent downregulation of the key metastasis-promoter Matrix Metalloproteinase-9 (MMP-9). Genetic inhibition of miR-155-5p or direct BACH1 inhibition phenocopied the effects of TQ, confirming the functional significance of this axis. Thus, we define a novel oncogenic signaling cascade—the hsa-miR-155-5p/BACH1/MMP-9 axis that is effectively disrupted by TQ. Conclusions: This represents the first evidence that TQ exerts its anti-cancer effects in LC through the modulation of the critical signaling cascade (hsa-miR-155-5p → BACH1 → MMP-9). Our findings establish TQ as a multi-targeted agent capable of simultaneously inhibiting miRNA-mediated oncogenic signaling and protein-level effectors. The dual therapeutic action of TQ represents a novel therapeutic strategy and underscores its potential for synergistic combination therapies. Full article