Cancer remains a leading global health challenge, necessitating the exploration of novel therapeutic strategies. Vitexin (apigenin-8-C-β-D-glucopyranoside), a natural flavonoid glycoside with a molecular weight of 432.38 g/mol, is derived from plants such as mung bean, beetroot, and hawthorn. This compound features a distinctive C-glycosidic bond at the 8-position of its apigenin backbone, contributing to its enhanced metabolic stability compared to O-glycosidic flavonoids. Preclinical studies demonstrate that vitexin modulates critical cellular processes such as cell cycle progression, apoptosis, autophagy, metastasis, angiogenesis, epigenetic modifications, and tumor glycolysis inhibition. It exerts its effects by targeting key signaling pathways, including phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and signal transducer and activator of transcription 3 (STAT3), and shows potential for combination therapies to enhance efficacy and overcome resistance. Advances in nanotechnology further enhance its bioavailability and delivery potential. This review comprehensively examines the current evidence on vitexin’s anticancer mechanisms, highlighting its multi-target therapeutic potential and future research directions.

Diethylhexyl phthalate (DEHP), a common environmental plasticizer, induces oxidative damage and cell apoptosis without efficient treatment. Tremella fuciformis polysaccharides (TFPs) are known natural antioxidants, yet their protection against DEHP toxicity remains unclear. This study aimed to investigate the protective effects of TFP against DEHP-induced toxicity using both human umbilical vein endothelial cells (HUVECs) and Caenorhabditis elegans models. The results demonstrate that TFPs significantly alleviated DEHP-induced cytotoxicity in HUVECs by reducing reactive oxygen species (ROS) generation and inhibiting mitochondrial apoptosis pathways, which may contribute to the activation of antioxidant systems mediating via Nrf-2. In C. elegans, TFP improved survival rates under DEHP stress and reduced ROS accumulation. This protection was associated with the modulation of the insulin-like pathway and skn-1 gene to increase the expressions of antioxidant genes. Our findings reveal that TFP exhibits protection against DEHP-induced oxidative stress and apoptosis through the synergistic regulation of survival and antioxidant pathways, highlighting its potential as a natural dietary intervention for environmental toxicant-induced health risks.

Dicyclohexyl phthalate (DCHP) is a widely used plasticizer, but its potential impact on immunity remains largely unexplored. In this study, synchronized L1-stage Caenorhabditis elegans were exposed to 0.0001–0.1 g/L DCHP for 72 h to investigate the effects of chronic early-life exposure on innate immunity; 0.01 and 0.1 g/L were used for subsequent mechanistic analyses. Innate immune function was evaluated using Pseudomonas aeruginosa PA14 survival assays, RT-qPCR, mutant strains, and oxidative-stress-related measurements. Chronic exposure beginning at the L1 stage significantly reduced the survival of C. elegans infected with Pseudomonas aeruginosa PA14. This immunosuppression was associated with increased daf-2 and age-1 transcript levels and reduced daf-16 transcript levels, indicating transcriptional alterations in insulin-like signaling-related genes. Additionally, the expression of pmk-1, nsy-1, and sek-1, key components of the p38 MAPK pathway, was markedly downregulated. Survival assays using different mutants supported the involvement of insulin-like signaling- and p38 MAPK-related genes in the decline in innate immunity following DCHP exposure. Furthermore, DCHP exposure reduced the expression of stress resistance genes, including skn-1, and several antioxidant enzymes. These findings suggest that DCHP may impair innate immune function through transcriptional alterations in immune- and stress-response pathways, although direct pathway activation or inhibition was not demonstrated.

As an emerging substitute for conventional phthalates, diphenyl phthalate (DPhP) raises growing environmental health concerns, yet its systemic toxicity profile remains poorly characterized. We used human umbilical vein endothelial cell (HUVEC) and Caenorhabditis elegans models to study the toxic effects and the underlying mechanisms of DPhP exposure. The results demonstrate that DPhP significantly suppresses cell viability and proliferation. Mechanistically, DPhP induces G1/S phase cell cycle alterations by upregulating cyclin-dependent kinase inhibitors (p21 and p27) and downregulating CDK-cyclin complexes, consistent with a stress-induced delay in cell cycle progression. In C. elegans, DPhP exposure impairs growth and locomotor behavior. Molecular analyses reveal that these adverse outcomes are associated with the dysregulation of key signaling pathways, including IIS, PI3K/AKT, and MAPK. Notably, DPhP disrupts the expression of neurodevelopmental genes, particularly those governing dopaminergic and cholinergic neurotransmission. Consistent with this finding, DPhP-exposed nematodes exhibit deficits in chemotaxis and learning, accompanied by reduced dopamine and GABA levels, and a loss of dopaminergic neurons, indicating substantial neurotoxicity. Collectively, this study provides comprehensive evidence that DPhP disrupts cellular growth, development, and neural function across models, highlighting its underappreciated health risks and offering crucial insights for environmental safety assessment