Tryptophan metabolism as a key integrator within the gut-lung-brain axis: Mechanistic insights and nutritional therapeutic strategies for inflammatory and neuropsychiatric disorders.

The Emerging Role of microRNAs as Targets of Phytochemical Intervention in Myocardial Infarction: A Systematic Review of In Vitro and In Vivo Studies.

Childhood overweight and obesity are growing public health concerns worldwide. Among dietary elements, dietary phytochemicals have been suggested to play a role in weight management. We aim to investigate the association between dietary phytochemical index (DPI) and the risk of overweight and obesity in primary school girls in Kerman City, Iran. Three hundred and thirty primary school girls between the ages of 6 and 12 entered this study. We used standard protocols for measuring anthropometric indices. Obesity and overweight were defined according to BMI-for-age Z-Score (BAZ) based on World Health Organization Z-Scores charts for girls aged 5-19 years old. The dietary phytochemical index was calculated using McCarty method. We assessed sociodemographic status and physical activity using valid questionnaires. Participants in higher tertile of DPI have significantly higher intakes of energy (p = 0.003), energy from phytochemical food groups (p < 0.001), fiber (p < 0.001), whole grains (p < 0.001), fruits (p < 0.001), vegetables (p < 0.001), and nuts and seeds (p < 0.001). A higher intake of supplements was associated with a higher DPI (8.5% vs. 3.9%; p = 0.034). Participants in the higher tertile compare with a lower tertile of DPI have significantly higher BAZ (0.47 ± 0.12 vs. 0.01 ± 0.12; p = 0.023). However, a significant direct association was revealed between DPI and overweight (OR 2.05; CI 1.02-4.15, p = 0.037). In conclusion, our findings suggest that a diet high in phytochemicals might be associated with a higher prevalence of overweight in children, but not obesity.

Dietary antioxidants and phytochemicals are believed to support cognitive health, but evidence on composite dietary indices remains limited. This cross-sectional study of 1845 community-dwelling older adults in China investigated the associations of the composite dietary antioxidant index (CDAI) and dietary phytochemical index (DPI) with cognitive function and mild cognitive impairment (MCI). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA; Beijing version). MCI was diagnosed through a two-stage procedure: MoCA-based preliminary screening (with education-stratified cutoffs: 13/14 for illiterate, 19/20 for 1–6 years, 24/25 for ≥7 years) followed by neurologist confirmation. CDAI was calculated as the sum of the standardized intakes of six antioxidants (selenium, zinc, carotenoids, vitamin A, vitamin C, vitamin E); DPI was defined as the percentage of the total energy intake from phytochemical-rich foods (fruits, vegetables excluding potatoes, legumes including soy products, nuts, seeds, and whole grains). Multivariable linear regression, logistic regression, and receiver operating characteristic (ROC) curve analyses were performed. The basal metabolic rate (BMR) and systemic immune-inflammation index (SII; platelets × neutrophils/lymphocytes) were tested as potential statistical mediators. Each one-unit increase in CDAI was associated with a 0.068-point higher MoCA score (95% CI: 0.012–0.123), and each one-unit increase in DPI was associated with a 0.029-point higher MoCA score (95% CI: 0.008–0.050). BMR and SII partially mediated the association between CDAI and MoCA score, but temporal ordering remains unclear due to the cross-sectional design. When both CDAI and DPI were in the highest quartile, participants had a 46.3% lower risk of MCI compared with those with both indices in the lowest quartile (OR = 0.537, 95% CI: 0.308–0.935). A predictive model incorporating CDAI, inflammatory markers, and red blood cell parameters showed moderate discriminatory ability in this study sample (apparent AUC = 0.731, bootstrap-corrected AUC = 0.728). These findings suggest that a higher combined dietary antioxidant and phytochemical intake may be jointly associated with better cognitive function, although the cross-sectional design precludes causal inference.

Obesity is linked to chronic inflammation, insulin resistance, and gut microbiota dysbiosis, partly via TMAO. This study investigates associations between dietary patterns, as indexed by the Dietary Phytochemical Index (DPI), with insulin resistance, inflammatory markers, and TMAO. In this cross-sectional study, 600 adults with obesity (BMI ≥ 30 kg/m²) without diagnosed comorbidities were evaluated. Dietary intake was assessed using a validated 110-item FFQ, and the DPI was computed. Fasting blood samples were analyzed for glucose, insulin, HOMA-IR, lipid profile, CRP, IL-6, TNF-α, LBP, adiponectin, and TMAO. Multivariable regression and mediation analyses were performed. Participants in the highest DPI quartile exhibited lower mean BMI, waist circumference, and fat mass compared to those in the lowest quartile. They also had lower fasting plasma glucose (4.52 ± 0.06 mmol/L vs. 5.92 ± 0.24 mmol/L; P < 0.001), lower insulin concentrations (65.6 ± 2.4 pmol/L vs. 120.4 ± 18.0 pmol/L; P < 0.001), and lower HOMA-IR values (1.90 ± 0.09 vs. 4.59 ± 0.82; P < 0.001). Higher DPI was associated with lower concentrations of CRP, TNF-α, and TMAO, and higher concentrations of adiponectin and HDL-C (all P < 0.001). Higher DPI was associated with lower systemic inflammation and better insulin sensitivity. These findings highlight the potential role of phytochemical-rich diets in supporting insulin resistance and metabolic disturbances among obese adults; however, prospective randomized controlled trials are required to confirm these associations and establish causality.

Phytochemicals and Obesity: A mini Review from the Dietary Phytochemical Index Perspective.

Comprehensive molecular and phenotypic characterization of tumor models is still needed for a robust understanding of breast cancer mechanisms and therapies. Here, we explore the genome, transcriptome, and proteome of treated and untreated 4T1 triple-negative breast cancer cells to integrate genomic vulnerabilities and mutational profiling with novel treatment-induced delivery, signaling, and apoptotic responses. Nanoencapsulation (AuNPs) of berry-derived polyphenolic compounds was influenced by limited clinical use due to poor stability and bioavailability. Several physicochemical characterizations employed include TEM, FTIR, and targeted UPLC/MS-QQQ assays. We identified significant mutations to breast cancer-related tumor suppressor genes (TP53, BRCA2, BARD1, CDH1, NF1, and CHEK2) and deciphered the functional consequences leveraging the higher throughput Illumina NovaSeq X and NextSeq sequencing and the highly accurate predictive power of AlphaFold. We found ~5,700,000 single-nucleotide variations (SNVs) and 329448 indels, achieving an important upgrade over existing literature data. Multiple sequence alignment with WT mouse and human protein sequences demonstrated that mutations present in 4T1 cells are within highly conserved motifs of key tumor suppressors, emphasizing their relevance to human breast cancer biology. Key findings from differentially expressed gene enrichment analyses (GSEA) revealed positive gene enrichments of DNA repair regulators and TGF-β signaling, while having negative enrichments of cell adhesion, cadherin and MAPK signaling via PI3K/AKT/MAPK/Wnt pathways, potentially influencing apoptosis and immune evasion intrinsic to cancer. Notably, decreased expression of PIK3CG, PALLD, PTPRZ1, and CDH8 and increased expression of SEMA6C, WWOX, NHEJ1, and MAML3 suggested suppression of epithelial-to-mesenchymal transition (EMT) and metastatic potential. Further assessment of immunohistochemical, immunofluorescent, and flow cytometric data revealed that berry-derived nanoparticles are associated with the modulation of oncogenic transcription factors and linked to induced caspase-dependent execution-phase ROS-mediated apoptosis through pPAK1Thr212 dephosphorylation, downregulation of pPI3Kp85αγ(Tyr467/199)/pAKT1Thr450/mTOR signaling, and modulation of pJAK3Tyr785/STAT3 pathway supporting transcriptomic and transcriptional reprogramming of 4T1 treated cells. Together, our findings uncover a new strategy to capture berry-derived polyphenols required to regulate apoptosis, autophagy, immune response, and metastasis-related gene networks in breast cancer, thereby underscoring the therapeutic potential of functionalized AuNPs as delivery platforms for dietary phytochemicals.

Human exposure to micro- and nanoplastics (MP/NPs) is increasingly recognized as a potential environmental health concern, although their role in reproductive carcinogenesis remains unclear. This narrative review aims to evaluate current evidence linking MP/NP exposure to reproductive cancers and to explore the potential chemoprotective effects of bioactive compounds derived from ginger, garlic, and turmeric. A structured literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar for studies published between 2008 and 2026. Relevant in vitro, in vivo, and human biomonitoring studies were included to assess mechanisms of toxicity, while preclinical and clinical studies were reviewed to examine the anticancer properties of selected dietary phytochemicals. Available evidence suggests that MP/NPs can accumulate in human biological systems, including reproductive tissues, where they induce oxidative stress, chronic inflammation, endocrine disruption, and DNA damage, processes closely associated with carcinogenesis. Although epidemiological data remain limited and do not establish cancer, emerging biomonitoring and experimental findings support a biologically plausible link between MP/NP exposure and hormone-related cancers. Concurrently, bioactive compounds such as curcuminoids, gingerols, and organosulfur compounds demonstrate the ability to modulate key molecular pathways involved in oxidative stress, inflammation, and cell proliferation. Preclinical studies consistently report anticancer effects, while early clinical evidence suggests improvements in oxidative and inflammatory biomarkers, though definitive therapeutic benefits remain uncertain. Overall, this review highlights important mechanistic links and identifies dietary phytochemicals as potential modulators of MP/NP-induced carcinogenic pathways. However, further well-designed epidemiological and clinical studies are needed to clarify causal relationships and validate their protective role.

Through the intake of dietary phytochemicals and herbal drugs, humans are exposed to a great number of natural products that can be either beneficial or detrimental to health outcomes. Phytochemicals from foods and medicinal plants, often referred to as secondary metabolites to emphasize their difference from metabolites produced by primary metabolism, contribute not just to occasional but long term or life-long exposure. While pharmacological actions of synthetic drugs are closely tied to changes in gene expression, the same holds true for foods and herbal drugs, but the wealth of research data is heterogeneous. This original review article attempts to clarify the exact mechanisms of gene regulation or expression by natural products through direct or indirect effects on transcription factors or epigenetic changes, with a focus on frequently occurring pathways and phytochemical classes. This review points at recent pharmaceutical drug development that arose from the investigation of natural products in food ingredients and herbal medicines and carefully evaluates negative effects on gene expression, which can lead to disease or reduced life expectancy. This article reviews seven relevant natural substance classes according to their approximate frequency in common foods and medicinal plants, and discusses general or more discrete effects on gene expression according to structure-activity relationships (SARs).

Dietary Phytochemicals and Nutraceuticals in Hormetic Modulation of Human Health: Molecular Mechanisms and Translational Perspectives

Nutraceutical potential of radish (Raphanus sativus cv. Tango) microgreens as sustainable and reproducible sources of hydrogen sulfide-releasing compounds.

Global diversity of arabinoxylans, alkylresorcinols and phenolic acids in 180 rye (Secale cereale L.) accessions: implications for functional food innovation.

Background/Objectives: Demand for functional foods is growing due to the desire to prevent cardiometabolic disorders. Pseudocereals, particularly quinoa, buckwheat, and amaranth, stand out for their functional properties related to cardiometabolic health. The dietary fiber, plant proteins, vitamins, minerals, and phytochemicals in pseudocereals primarily help to regulate glycemic response and lipid profile, as well as blood pressure. The aim of this review is to briefly explain the role of pseudocereals in biological mechanisms underlying cardiometabolic effects and evaluate the findings of human studies. Methods: The biological mechanisms that emphasize potential cardiometabolic effects of pseudocereals were summarized based on preclinical studies. Human studies were searched on Web of Science, PubMed, and ScienceDirect between June and December 2025. Findings of human studies on potential cardiometabolic health benefits of pseudocereals, including their anti-hyperlipidemic, anti-hyperglycemic, anti-obesity, and anti-hypertensive effects, are discussed. Results: The revealed mechanisms in preclinical studies and current outcomes of thirty-three human studies included in this review indicated that pseudocereals, especially quinoa and buckwheat, might be a part of healthy nutrition to assist the prevention and management of cardiometabolic disorders. In human studies, the most notable improvements were reported in plasma triglyceride and total cholesterol levels. Nevertheless, the number of human studies is limited, and existing studies have methodological variations to state cumulative and evidence-based consumption recommendations. Conclusions: Despite the potential protective effects of pseudocereals on cardiometabolic health, well-designed, controlled human studies are needed to elucidate the outcomes and provide clear evidence of the role of pseudocereals in relation to cardiometabolic effects.

Age-accompanied chronic, low-grade systemic inflammation (inflammaging) drives the onset and progression of neurodegenerative disorders like Parkinson’s disease (PD). Currently, no disease-modifying therapies are available for PD. Exposure to environmental toxicants, including paraquat (PQ), rotenone, and neurotoxic metals, increases disease risk. Conversely, sustained consumption of dietary soft electrophiles, such as flavonoids, carotenoids, vitamin E vitamers, and essential fatty acids, has been associated with increased lifespan and delayed age-related neurological decline. Omega-3 and select omega-6 fatty acids also serve as precursors of lipid-derived specialized pro-resolving mediators (SPMs), which exert potent anti-inflammatory and inflammation-resolving activities. Here, we report the development of a robust analytical method to quantify pro-resolving oxylipins in a PQ-inducedDrosophila melanogastermodel of PD, enabling investigation of how dietary phytochemicals modulate anti-inflammatory and pro-resolving lipid metabolismin vivo. We hypothesized that plant-derived soft electrophiles promote active resolution of neuroinflammation by enhancing the production of pro-resolving oxylipins derived from essential fatty acids, and that their neuroprotective effects are linked to their soft electrophilic properties. Our results demonstrate that specific lipophilic plant-derived soft electrophiles significantly upregulate pro-resolving oxylipins inDrosophilaheads following PQ exposure. We identify a subset of flavones and structurally related phytochemicals that selectively enhance SPM biosynthesis and show that this response involves the NF-κB orthologuerelish. Additionally, feeding modality and sex-specific dimorphisms were found to influence oxylipin production. Collectively, these findings indicate that structurally related dietary soft electrophiles enhance endogenous pro-resolving lipid pathways, promote resolution of toxin-induced neuroinflammation, and have potential preventive and therapeutic relevance for neuroinflammation-associated neurodegenerative diseases.HighlightsQuantification of pro-resolving lipids in aDrosophilaParkinson’s model.Specific structural features of phytochemicals contribute toin vivobioactivity.Lipophilic soft electrophiles show therapeutic potential against neuroinflammation.Feeding modality and sexual dimorphism also regulate oxylipin production.Graphical abstract

Harnessing cancer chemotherapy with dietary phytochemicals by nanotechnology

Dietary phytochemicals as multitarget strategies against metabolic syndrome: Mechanistic basis and translational outlook

Bile acids (BAs), classically regarded as detergents for dietary lipid absorption, have emerged as pivotal signaling molecules with systemic endocrine functions. The discovery of the Farnesoid X Receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5) as BAs-activated receptors unveiled their profound influences on glucose, lipid, and energy metabolism. BAs are first synthesized in hepatocytes and further metabolized by gut microbes, can either circulate in enterohepatic system or be found in circulations to exert various effects. More recently, the gut-brain axis has been identified as a critical pathway through which BAs exert significant effects on central nervous system (CNS) function and health. Based on research progresses mentioned above, this review systematically delineates the synthesis, metabolism, and classification of BAs, with a focus on the intricate crosstalk between the hepatic-gut BA axis and the brain. In addition, we explore the compelling evidences linking BAs dysregulation to a spectrum of neurological disorders, including neurodegenerative diseases (Alzheimer's and Parkinson's disease), depression, and hepatic encephalopathy. Besides, the potential mechanisms, such as alleviating neuroinflammation, maintaining the integrity of blood-brain barrier, increasing the neuronal survival, and modulating neurotransmitter systems are further elucidated. Finally, strategies of dietary intervention through phytochemicals to modulate the BAs pool for improved neurological outcomes are summarized and discussed. By integrating pre-clinical and clinical findings, this review aims to establish a foundation for understanding BAs as novel therapeutic targets in neurology and nutritional neuroscience.

• Phytochemicals in olive and black seed exhibit biphasic hormetic responses. • Hormesis involves beneficial effects at low doses, harmful at high doses. • Understanding molecular mechanisms aids in treating metabolic and age-related diseases. • Precise dosing within hormetic zones enhances therapeutic benefits and reduces risks. • Study emphasizes bioactive compounds' potential for disease prevention and health. Hormesis is defined as the biphasic dose response relationship which determines the dual activity of a phytochemical. In other words, when the same drug exhibits both beneficial and harmful effects at different concentrations. Phytochemicals present with considerable amounts in medicinal plants, especially Olea europaea L. (olive) and Nigella sativa L. (black seed) have multifaceted mechanisms which also demonstrate hormetic responses, as stated in various studies. Though these activities are known for decades, clinical implications of these mechanisms are less studied. Hence, a thorough understanding of hormetic responses at cellular and molecular level is essential for further research in the treatment of metabolic, chronic inflammation, and age-related disorders. Therefore, the aim of the current comprehensive review was to emphasize the importance of molecular hormetic mechanisms of bioactive compounds from Olea europaea L. (olive) and Nigella sativa L. (black seed) and focuses on their therapeutic potential for enhancing human health from disease prevention. Precise understanding of optimal dosage within hormetic zones is essential for ameliorated therapeutic effects that benefit various diseases and reduced off-target effects, adverse effects, etc., and improve the quality of life.

Radish sprouts (Raphanus sativus L.) are rich in dietary fibers and phytochemicals with antioxidant and anti-inflammatory activities. However, their whole-food effects on the gut-brain axis remain poorly defined. This study examined the preventive potential of whole-food red radish sprout (RS) powder against high-fat diet (HFD)-induced obesity and cognitive decline in mice, focusing on its effects on barrier integrity, inflammation, oxidative stress, and gut microbiota. Male C57BL/6 mice were fed an HFD for 16weeks with or without RS powder (low or high dose). Assessments included body and tissue indices, oral glucose tolerance, serum leptin, cognitive performance, oxidative stress in brain, gene expression of tight junction and inflammatory markers in colon and brain, and fecal microbiota profiling using 16S rRNA sequencing. RS supplementation attenuated HFD-induced weight gain, improved glucose tolerance, and reduced leptin levels, with stronger effects at the higher dose. Cognitive deficits were rescued by RS, accompanied by alleviation of brain oxidative stress and reduced expression of neuroinflammatory genes (Tnf, Il6, Il1b, Aif1, Gfap). RS restored tight-junction genes (Tjp1, Ocln, Cldn1, Jam2, Cdh5) while simultaneously decreasing Cldn2 and pro-inflammatory transcripts, and upregulating Il10. Although alpha diversity was unchanged, beta diversity differed significantly; RS reduced the Firmicutes/Bacteroidota ratio, enriched Akkermansia and Lactobacillus, and suppressed Oscillibacter and Desulfovibrio. Whole-food RS powder prevents HFD-induced obesity and cognitive decline by reinforcing barrier integrity, reducing inflammation and oxidative stress, and reshaping gut microbiota. These findings support RS as a practical functional food for early obesity intervention via gut-brain axis regulation.

Dietary phytochemicals, primarily derived from grasses, legumes, and agro-industrial byproducts of plant origin, encompass distinct chemical classes such as polyphenols (including tannins, flavonoids, and other polyphenol compounds), saponins, organosulfur compounds, and essential oils (largely composed of terpenoids and phenylpropanoids). These compounds can function as rumen modifiers, antimethanogenic agents, anthelmintics, growth promoters, stress mitigators, and biopreservatives in ruminant production systems. Thus, they improve feed efficiency, nutrient utilization, and nitrogen retention while mitigating greenhouse gas emissions. In dairy systems specifically, phytogenic feedstuffs enhance milk yield and composition by enriching conjugated linoleic acids (CLAs), omega-3 fatty acids, and antioxidant compounds, leading to superior nutritional and oxidative stability. In meat production systems, they improve tenderness, flavor and shelf life through reduced oxidation and enhanced muscle metabolism. Despite these benefits, dose optimization, bio-efficacy, and species-specific responses remain critical research priorities. Use of phytogenic-based feeding strategies aligns with global sustainability goals by reducing reliance on feed additives, promoting environmentally resilient and circular food systems. This review synthesizes emerging evidence on the mechanisms, production outcomes, and functional benefits of dietary phytochemicals, providing a scientific framework for their strategic application in sustainable ruminant milk and meat production.