Search Results (1,545)

P-glycoprotein (P-gp), an efflux transporter highly expressed in renal tubules, plays a crucial role in the detoxification and protection of barrier/excretory tissues from harmful xenobiotics. Xanthones and thioxanthones (TXs) are known for their antimicrobial and antitumor activities and for their ability to modulate membrane transporters such as P-gp. Previous studies have reported that (thio)xanthonic derivatives enhance P-gp expression and/or activity in intestinal cells, reducing the intracellular accumulation of toxic substrates; however, their capacity to modulate P-gp in renal cells remains poorly explored. This study aimed to predict, in silico, TXs’ binding sites within P-gp and to evaluate, in vitro, in human kidney (HK)-2 cells, the effects of selected TXs (TX1–5) on P-gp activity and expression, and protection against cisplatin-induced cytotoxicity. Computational studies identified preferential TX1–5 binding to the drug-binding pocket, particularly the rhodamine 123 (R) or modulator (M) sites, and to nucleotide-binding domain 1. In vitro, rhodamine 123 accumulation assays revealed increased P-gp transport activity after 120 min or 24 h exposure to TX1–5, except TX4. TX2 elicited the strongest effect (141% increase, p < 0.0001), upregulated P-gp expression (24 h, p < 0.0001), and significantly protected HK-2 cells from cisplatin-induced cytotoxicity (increased IC₅₀, p < 0.0001). Altogether, these findings position thioxanthones as promising scaffolds for the development of P-gp-targeted strategies to mitigate drug-induced nephrotoxicity. Full article

Seasonal environmental conditions can modulate the chemical composition and biological activity of essential oils from medicinal plants. This study investigated the phytochemical profile, antioxidant potential, cytotoxic activity, and cytoprotective effects of Lippia alba essential oils collected during dry and rainy seasons. Gas chromatography analysis revealed that all samples preserved a citral chemotype. Principal Component Analysis (PCA) confirmed citral as the primary discriminant metabolite, while quantitative seasonal variations were mainly associated with minor oxygenated monoterpenes, particularly geraniol, carvone, and nerolidol. The essential oil obtained during the rainy season (A5T–RS) exhibited significantly higher antioxidant activity, as determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, total antioxidant capacity, and hydrogen peroxide scavenging assays. Intracellular reactive oxygen species (ROS) evaluation using the 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) method demonstrated that both oils reduced oxidative stress in murine fibroblasts—L929, with enhanced cytoprotective effects observed for A5T–RS. Cytotoxicity assays against non-tumor (murine fibroblast-NIH/3T3, L929, Chinese hamster ovary—CHO-K1) and tumor (human cervical carcinoma—HeLa, and human hepatocellular carcinoma—HepG2) cell lines revealed selective antiproliferative activity, with tumor cells displaying greater sensitivity, particularly to the rainy-season oil. These results demonstrate that seasonal metabolomic modulation enhances the biological performance of L. alba essential oil without altering its chemotypic identity, highlighting the importance of environmental factors in the development of bioactive plant-derived products. Full article

Purpose: Osteotoxicity is a well-recognized adverse effect of Methotrexate (MTX) therapy, primarily driven by oxidative stress and impaired bone remodeling. This study aimed to investigate the protective effects of Tempol, a membrane-permeable nitroxide antioxidant, against MTX-induced osteotoxicity, and to assess how these effects are influenced by ML210, a glutathione peroxidase 4 (GPX4) inhibitor. Methods: Murine osteocyte-like MLO-Y4 cells were treated with MTX alone, Tempol alone, or a combination of MTX with Tempol and ML210. Apoptotic markers (caspase-3, Bax, Bcl-2), MAPK signaling proteins (p-JNK, p-ERK), and oxidative stress parameters (TAS, TOS, SOD, GPx) were measured via ELISA to evaluate the redox and apoptotic responses. Results: MTX significantly induced apoptosis, as evidenced by increased caspase-3 activity and Bax expression, along with decreased Bcl-2 levels. MTX also activated the MAPK pathway by upregulating p-JNK and p-ERK. Furthermore, MTX decreased TAS, SOD, and GPx levels, while increasing TOS. Tempol treatment successfully reversed these effects, restoring apoptotic balance, inhibiting MAPK activation, and enhancing antioxidant capacity. However, co-treatment with ML210 markedly attenuated Tempol’s protective effects, resulting in sustained oxidative stress, elevated apoptotic markers, and persistent MAPK pathway activation. This suggests that Tempol’s cytoprotective actions are dependent on functional GPX4 activity. Conclusion: Tempol exhibits strong potential as an adjunctive antioxidant therapy to counteract MTX-induced osteotoxicity. Nevertheless, its efficacy is significantly influenced by the status of the endogenous antioxidant enzyme GPX4. These findings underscore the need for further investigation into Tempol’s mechanism of action in redox-dependent pathways and its suitability in clinical settings, especially where GPX4 function may be compromised. Full article

Background/Objectives: Alzheimer’s disease (AD) involves amyloid and tau pathology with neuroimmune dysregulation, and Yixin Yangshen Granules (YXYS) shows neuroprotective promise, though mechanisms remain unclear. This study aimed to elucidate the multi-target mechanisms of YXYS in AD. Methods: The study began by analyzing a public human AD hippocampal snRNA-seq dataset to identify cell-type-specific pathological pathways and profiled YXYS constituents by UPLC-QTOF-MS. In vitro, YXYS cytoprotection against mitochondrial dysfunction and oxidative stress was tested in Aβ_25–35-challenged HT22 cells; in vivo efficacy was assessed in Aβ_1–42-induced mice via behavioral and histopathological analyses. Integrated transcriptomic and proteomic profiling of brain tissue, with ELISA, qRT-PCR, and Western blot validation, confirmed pathway targets. Using the intersection of transcriptomic and proteomic targets as biological input, the DTIAM deep learning framework was employed to prioritize active YXYS constituents. Finally, molecular docking and 100-ns dynamics simulations demonstrated direct binding of Ganosporelactone A to HIF−1α. Results: AD snRNA-seq analysis highlighted HIF−1 and AGE-RAGE signaling as prominent pathways in the AD hippocampus, particularly enriched in brain microvascular endothelial cells, implicating neurovascular hypoxic and inflammatory stress. In Aβ-induced mice, YXYS improved cognition, reduced Aβ pathology, suppressed neuroinflammation, and promoted neuronal survival, consistent with in vitro evidence of restored mitochondrial function. Multi-omics confirmed convergence on HIF−1 and AGE-RAGE pathways, with YXYS rebalancing the neuroimmune microenvironment by reducing pro-inflammatory M0 macrophages. Screening against these consensus signaling hubs, deep learning analysis prioritized Ganosporelactone A as the top-ranked modulator, and molecular further demonstrated the stable binding of Ganosporelactone A to HIF−1α, linking YXYS to mitigation of hypoxic stress. Conclusions: Guided by multi-omics and deep learning, our findings suggest that YXYS may alleviate AD-related phenotypes through multi-target modulation of the HIF−1 and AGE-RAGE pathways, with associated improvements in neuro-immune homeostasis and reductions in oxidative stress, neuroinflammation, and hypoxia. Full article

Heat stress (HS), induced by global climate warming, is one of the major limiting factors in edible fungi production. HS suppresses mycelial growth and fruiting body formation by causing excessive accumulation of intracellular reactive oxygen species (ROS), disrupting the integrity of cell membranes and cell walls, and impairing cellular metabolism. Increasing evidence suggests that the application of exogenous substances (ESs) effectively mitigates HS in edible fungi. Based on the recent literature, this review categorizes ESs into three groups—core signaling molecules, plant growth regulators, and cytoprotective agents—and summarizes their beneficial effects against HS in edible fungi. The underlying mechanisms of ES-mediated alleviation of heat-induced damage primarily involve four pathways: (1) regulation of antioxidant systems; (2) preservation of cell wall and membrane structural integrity; (3) modulation of defense-related gene expression; and (4) regulation of carbon metabolic flux. Current challenges and corresponding strategies are discussed to provide a reference for elucidating the mechanisms by which ESs alleviate HS and to promote their practical application in edible fungi production. Full article

The nuclear factor erythroid 2–related factor 2 (NRF2) is a master transcription factor that orchestrates cellular defense against oxidative and electrophilic stress. Dysregulation of the KEAP1–NRF2–ARE pathway has been implicated in several dermatological disorders, including vitiligo, psoriasis, atopic dermatitis, photoaging, and radiation dermatitis. This review summarizes recent advances in the understanding of NRF2 activation mechanisms and highlights pharmacological and natural compounds with potential dermatological applications. A comprehensive analysis of natural, semisynthetic, and synthetic NRF2 modulators is provided, describing their chemical structures, synthetic approaches, mechanisms of action, preclinical and clinical evidence, and therapeutic relevance for skin disorders. Multiple classes of NRF2 activators, including isothiocyanates such as sulforaphane, triterpenoids such as omaveloxolone, flavonoids including baicalein and apigenin, alkaloids such as berberine, glycosides like afzelin and paeoniflorin, stilbenoids such as tapinarof, and α,β-unsaturated fumaric acid esters such as dimethyl fumarate, have demonstrated antioxidant, anti-inflammatory, and cytoprotective effects in keratinocytes and melanocytes. Some of these agents, particularly dimethyl fumarate and tapinarof, have advanced to clinical development or commercialization, whereas others remain at the preclinical stage but show encouraging results in animal models and cell culture systems. Overall, pharmacological activation of NRF2 represents a promising therapeutic strategy to counteract oxidative stress–driven skin damage and inflammation; however, continued translational and clinical research is required to optimize formulations, dosing regimens, and safety profiles for integration into dermatological practice. Full article

Background: Fibromyalgia (FM) and eating disorders (ED) represent distinct clinical entities traditionally managed within separate medical specialties, yet emerging evidence suggests significant comorbidity and potential shared pathophysiological mechanisms. Both conditions disproportionately affect women, involve complex multifactorial etiologies and substantially impair quality of life. Despite documented clinical overlaps, the mechanistic connections linking these conditions remain poorly characterized, and integrated treatment approaches are lacking. Objective: This narrative review examines the role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway dysfunction as a unifying molecular mechanism connecting fibromyalgia and eating disorders, with emphasis on implications for integrated rehabilitation strategies. Methods: We synthesized current evidence on oxidative stress pathophysiology in fibromyalgia and eating disorders, focusing on Nrf2-Keap1 pathway function, clinical comorbidity patterns and rehabilitation interventions targeting antioxidant defense mechanisms. In PubMed, representative search strings included “(fibromyalgia [MeSH] OR fibromyalgia [Title/Abstract]) AND (“eating disorders” [MeSH] OR “anorexia nervosa” [MeSH] OR “bulimia nervosa” [MeSH])” and “fibromyalgia AND (“oxidative stress” OR Nrf2 OR “redox”)”. Articles in English published through December 2025 were considered, with additional records identified by manually screening reference lists. Results: Fibromyalgia patients exhibit elevated oxidative stress markers, impaired antioxidant enzyme function and compromised Nrf2 activity correlating with disease severity, with studies reporting approximately 30–50% reductions in coenzyme Q10 levels compared with healthy controls. Similarly, eating disorders demonstrate mitochondrial dysfunction and oxidative stress dysregulation, though patterns differ across eating disorder phenotypes. Nrf2 serves as the master regulator of cellular antioxidant defense, coordinating expression of over 500 genes involved in detoxification, cytoprotection, inflammation modulation and metabolic regulation. Evidence suggests Nrf2 activity is regulated by energy balance, potentially linking nutritional status with cellular stress responses. Rehabilitation interventions, including graduated exercise and nutritional optimization with Nrf2-activating foods (cruciferous vegetables, polyphenols, omega-3 fatty acids), offer mechanism-based therapeutic approaches through hormetic Nrf2 activation and direct Keap1 modification. Conclusions: Multidisciplinary rehabilitation programs integrating physical therapy, exercise prescription and nutritional strategies targeting Nrf2 activation offer evidence-based, mechanism-driven approaches to address shared oxidative stress pathophysiology. Nrf2 pathway dysfunction represents a promising and biologically plausible molecular target that may help to unify our understanding of fibromyalgia and eating disorders pending confirmation from prospective clinical studies in comorbid populations. Future research should prioritize prospective clinical trials testing Nrf2-targeted interventions in comorbid populations and collaborative patient-centered care models. Full article

The roots of Panax ginseng are well known for their bioactive properties, while its berries have recently attracted attention for their pharmacological potential. This study investigated whether fermentation with Lactiplantibacillus plantarum enhances the antioxidant properties of ginseng roots and berries and their protective effects against oxidative stress in vitro. Fermentation significantly increased total polyphenol, flavonoid, and saponin contents and promoted the conversion of major ginsenosides (ginsenoside Rg1, ginsenoside Rb1, and ginsenoside Rb2), which are relatively less bioavailable, into minor ginsenosides (ginsenoside Rh1, ginsenoside Rg2, and ginsenoside Rg3) with enhanced biological activity and bioavailability. Fermented extracts exhibited higher radical-scavenging activities in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays than non-fermented extracts. In tert-butyl hydroperoxide (t-BHP)-stimulated Chang liver cells, fermented extracts reduced intracellular reactive oxygen species (ROS) generation, inhibited lipid peroxidation, restored the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio, and enhanced antioxidant enzyme activities, including superoxide dismutase (SOD) and catalase (CAT). These results demonstrate that L. plantarum-mediated fermentation effectively enhances the antioxidant and cytoprotective potential of ginseng roots and berries, supporting their application as functional food ingredients. Full article

This review presents an innovative and timely exploration of how cytoprotection can serve as a cohesive therapeutic approach by which to address the hemorrhage–thrombosis paradox. Presenting counteraction of both hemorrhage and thrombosis as phase-dependent outcomes of vascular dysregulation, the manuscript synthesizes conceptual, experimental, and clinical evidence into a unified systems-level model focused on the stable gastric pentadecapeptide BPC 157, which acts as a cytoprotective mediator. In rodents, BPC 157 can simultaneously counteract hemorrhage and thrombosis without directly affecting the coagulation cascade (aggregometry, thromboelastometry). This cytoprotective framework (decreased hemorrhage, decreased thrombosis) stands with presentation of both hemorrhage and thrombosis in the wound, arrhythmias, and Virchow triad, and resolution of these disturbances. As proof of the concept (full cytoprotective effect), a vasoprotective cytoprotective mediator capable of bidirectional regulation, BPC 157, is effective for wound healing, arrhythmia control, and normalization of Virchow’s triad (i.e., following major injuries, occlusion/occlusion-like syndromes). As a comparison from a cytoprotective (partial vs. full) standpoint, conventional agents—anticoagulants, antiplatelet drugs, and fibrinolytics—provide only partial protection by targeting isolated components of hemostasis. Beta blockers, calcium channel blockers, prostaglandins, NO modulators, ACE inhibitors, and statins each exert broader cytoprotective effects; however, these actions remain incomplete and context-dependent, typically unidirectional, dose-limited, or are achieved at the expense of opposing pathological risks. Contrarily, for BPC 157, decreased hemorrhage (including both anticoagulants and antiplatelet agents), decreased thrombosis, effective wound healing, arrhythmia control, and normalization of Virchow’s triad involve preservation of endothelial integrity, normalization of microcirculation, modulation of the NO system, stabilization of hemostatic balance, and recruitment of adaptive collateral pathways. Nevertheless, reliance on preclinical models necessitates further clinical validation. Full article

Postprandial hyperglycemia represents a critical therapeutic target in type 2 diabetes mellitus (T2DM), requiring interventions that simultaneously address glycemic dysregulation and oxidative stress. This study evaluated the anti-hyperglycemic and antioxidant properties of Sclerocarya birrea leaf crude extract (CE) and biosynthesized silver nanoparticles (AgNPs). Phytochemical screening, nanoparticle characterization (UV–Vis, XRD, TEM, SEM, DLS, FTIR), enzyme inhibition assays (α-amylase, α-glucosidase, DPP-IV), glucose dynamics in Caco-2 cells, and antioxidant assays (DPPH, total antioxidant capacity, H₂O₂ cytoprotection) were performed. Phytochemical analysis identified flavonoids, tannins, alkaloids, and terpenoids as major constituents of Sclerocarya birrea leaf extract. AgNPs exhibited spherical morphology (36.8 ± 8.6 nm, n = 100 particles analyzed), face-centered cubic crystallinity (crystallite size: 32.1 nm), and characteristic surface plasmon resonance at 451 nm. Both formulations inhibited α-amylase (CE IC₅₀: 14 µg/mL; AgNPs IC₅₀: 14.07 µg/mL, n = 3) and α-glucosidase (CE IC₅₀: 15.96 µg/mL; AgNPs IC₅₀: 15.82 µg/mL, n = 3), showing substantial inhibition, though less potent than acarbose. Uniquely, AgNPs demonstrated selective DPP-IV inhibition (IC₅₀: 220.5 µg/mL, n = 3, p < 0.001 vs. CE), completely absent in CE. In antioxidant assays, DPPH scavenging potency was comparable between formulations (CE IC₅₀: 23.45 µg/mL; AgNPs IC₅₀: 22.26 µg/mL, n = 3), while CE achieved higher maximal scavenging at the tested concentrations. Conversely, AgNPs provided superior intracellular cytoprotection against H₂O₂-induced oxidative stress in kidney cells (80.2 ± 2.1% viability at 76 µg/mL vs. CE 69.8 ± 3.4% at 190 µg/mL, n = 3, p < 0.001), representing a 2.5-fold dose advantage. Neither formulation significantly altered glucose uptake or SGLT1 expression in intestinal epithelial cells (p > 0.05, two-way ANOVA, n = 3). These findings establish S. birrea-based formulations, particularly AgNPs, as promising multifunctional candidates for managing postprandial hyperglycemia and oxidative complications in T2DM. They also highlight nanotechnology-enhanced phytomedicine as an innovative therapeutic strategy. Full article

Boron compounds, classified as prohibited food additives due to their high toxicity, persist in pesticides and fertilisers, industrial processes, food supply chains, and consumer goods, perpetuating multisource exposure risks. Chronic ingestion may induce fatal hepatorenal injury; however, mechanistic insights and epidemiological surveillance remain critically lacking amidst sector-wide regulatory gaps. This study employed integrated cellular and organismal models to elucidate the relationship between boron-induced hepatotoxicity and ferroptosis. We demonstrate that dietary boron accumulation in chicken livers is associated with histopathological damage, mitochondrial cristae dissolution and atrophy (a hallmark of ferroptosis), and elevated serum biomarkers AST and ALT. Boron exacerbates oxidative damage in hepatocytes by elevating malondialdehyde (MDA) production while modulating the Nrf2/ARE antioxidant signaling pathway—specifically downregulating key genes (Nrf2, HO-1, GCLM, CAT). Concurrently, it inhibits critical antioxidant enzymes (SOD, T-AOC), thereby depleting cellular antioxidant defenses. Crucially, boron disrupts iron homeostasis and induces ferroptosis by dysregulating the SLC7A11-GPX4 pathway: upregulating pro-ferroptotic genes (ACSL4, TF, TFR) and downregulating cytoprotective genes (SLC7A11, GPX4, FTH1). Co-treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1) attenuated boron-induced oxidative damage, whereas the ferroptosis inducer Erastin potentiated toxicity. Collectively, we pioneer the dual-pathogenic mechanism of boron hepatotoxicity—oxidative stress and ferroptotic cell death—establishing the SLC7A11/GPX4 axis as a novel therapeutic target against boron toxicity. Full article

Artocarpin, a prenylated flavonoid isolated from Artocarpus altilis heartwood, has emerged as a promising multi-targeted bioactive compound for combating UV-induced skin aging. This review provides a comprehensive overview of the molecular mechanisms and photoprotective efficacy of artocarpin across in vitro, in vivo and clinical study, based on the peer-reviewed literature published between 2012 and 2025, retrieved from PubMed, Scopus, and Web of Science. Delivery strategies designed to overcome the inherent physicochemical limitations of artocarpin on skin penetration are also discussed. Artocarpin demonstrates antioxidant effects through both direct free radical scavenging and activation of the Nrf2-ARE pathway, providing sustained cellular defense. Its anti-inflammatory properties target multiple signaling cascades, including the NF-κB and MAPK pathways, effectively mitigating UV-induced inflammatory response. The compound maintains dermal matrix homeostasis by inhibiting matrix metalloproteinase-1 (MMP-1) expression while preserving collagen synthesis and fibroblast mechanical function. Additionally, artocarpin exhibits selective apoptosis modulation, being cytoprotective in normal keratinocytes while acting as pro-apoptotic in damaged or abnormal cells, thereby supporting tissue homeostasis. It also inhibits melanogenesis through anti-inflammatory mechanisms rather than direct tyrosinase inhibition. Furthermore, artocarpin has been shown to induce autophagic cell death in certain cell lines; however, its role in UV-induced skin damages remains to be clarified. Despite these promising biological activities, the poor water solubility (<0.1 mg/mL) and high lipophilicity (log P ≈ 5) of artocarpin significantly limit its skin penetration. Lipid-based delivery systems, including liposomes, transfersomes, ethosomes, and nanostructured lipid carriers (NLCs), are presented as effective strategies to enhance transepidermal delivery, with each system offering distinct mechanistic advantages. Further investigations should prioritize the safety of artocarpin within each delivery system, as well as the synergistic co-encapsulation with complementary natural antioxidants to simultaneously target multiple mechanisms involved in UV-induced skin damage, thereby broadening its application in the cosmeceutical industry. Full article

Taxifolin, a natural flavonoid, consistently exerts cytoprotective effects against various oxidative stresses. In this study, we systematically evaluated its photoprotective efficacy and underlying mechanisms against ultraviolet B (UVB)-induced injury in human immortalized keratinocytes (HaCaT). Cell viability and apoptosis were assessed by MTT, fluorescence staining, and flow cytometry, while integrative transcriptomic and proteomic analyses were employed to identify core pathways and key mediators. Taxifolin exhibited antioxidant capacity comparable to that of ascorbic acid under identical in vitro radical-scavenging assays. Moreover, it displayed a strong absorption peak at 289 nm that overlaps the UVB spectrum (280–320 nm), enabling it to act as a chemical sunscreen. In UVB-challenged HaCaT cells, taxifolin markedly reduced intracellular reactive oxygen species (ROS) and attenuated JNK/p38 MAPK activation, as evidenced by Western blot, thereby breaking the ROS-MAPK vicious cycle. Multi-omics revealed that taxifolin was associated with attenuation of UVB-imposed G1/S arrest concomitant with restored Cyclin expression, while up-regulating MYC, FOXQ1, HMOX1 and AP-1 components c-Jun/c-Fos and thereby switching on a pro-survival transcriptional program. Consequently, apoptosis was suppressed and survival was significantly improved. Collectively, taxifolin integrated chemical filtration, ROS scavenging and signaling modulation to support a multi-target photoprotective network, which provides mechanistic insight into taxifolin-mediated cytoprotection and identifies candidate molecular nodes for further validation. Full article

Background/Objectives: Hepatic encephalopathy (HE) is characterized by hyperammonemia, neuroinflammation, oxidative stress, and blood–brain barrier (BBB) dysfunction, with brain endothelial cells being highly vulnerable to ammonia-induced damage. Adiponectin is a cytoprotective adipokine that may enhance endothelial resilience; however, its specific role under hyperammonemic conditions remains unclear. This study aims to investigate the protective effects of adiponectin on brain endothelial function and BBB integrity. Methods: In vivo, male C57BL/6J mice underwent bile duct ligation (BDL) surgery and received daily intraperitoneal adiponectin injections (10 μg/kg/day) for 6 days, starting 5 days post-surgery. On day 11, brain tissues and serum were collected for molecular and cytokine analyses. In vitro, mouse brain endothelial cells (bEnd.3) were pretreated with adiponectin before exposure to ammonia. Assays for tight junction preservation, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and total RNA sequencing were performed. Results: In BDL mice, adiponectin increased the expression of the tight junction protein claudin-5 and synaptic marker PSD95 across the cortex, hippocampus, and striatum, while reducing pro-oxidant (Cyp2e1, Cyp4a1) and apoptotic (Caspase-9) markers. In vitro, adiponectin pretreatment maintained tight junction proteins, suppressed inflammatory markers, restored mitochondrial membrane potential, and decreased ROS generation in ammonia-exposed bEnd.3 cells. Transcriptomic profiling revealed that adiponectin modulates stress-related gene expression under hyperammonemic conditions. Conclusions: Adiponectin enhances cellular stress resistance and maintains BBB structural integrity under ammonia-induced toxicity. These findings suggest that adiponectin serves as a promising therapeutic target for mitigating neurovascular unit dysfunction in hepatic encephalopathy. Full article

Mycotoxins are the most frequently occurring natural contaminant in food and feed products. Through the deployment of diverse agricultural strategies or biological, chemical, or physical treatments of crop products, mycotoxin contamination remains a persistent issue for the agricultural sector and food/feed industry. We previously suggested that halophytes, thanks to their high antioxidant activity, could protect animal cell lines from mycotoxin contamination. Here, a hydroalcoholic extract of Calystegia soldanella L. leaves was evaluated for in vitro total antioxidant capacity (TAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-quenching bioassays, as well as anti-inflammatory (ELISA measurement of IL-8 secretion), ROS-inhibiting production (CellROX Green assay), and calcium influx restoration (fluorescent probe Fura2-QBT assay) activities in two animal cells upon mycotoxin intoxication. C. soldanella extract displayed high antioxidant activities (DPPH IC₅₀ < 80 μg·mL⁻¹ and TAC of 90 mg AAE·g⁻¹ DW. Moreover, it exhibited a significant protective action on renal (MDBK) and intestinal (IPEC-J2) cells against zearalenone (ZEA) or T2-toxin contamination, restoring about 75% of cell viability (MTS bioassay) at 1 μg·mL⁻¹. This effect was accompanied by strong anti-inflammatory, ROS-inhibition, and membrane integrity restoration activities. A bio-guided study revealed that the fraction of C. soldanella extract eluted from C18-bound silica with 60% methanol was the most active one. Upon HPLC and 1D- and 2D-NMR analyses, major compounds identified in this fraction were flavonol-type flavonoids, including quercetin-3-O-glucose (X1), quercetin-3-O-rutinoside (X2), and quercetin-3-O-glucose-6″-acetate (X3). Enriched sub-fractions containing these compounds largely contributed to the cytoprotective effects of C. soldanella, supporting its potential use as a food/feed ingredient. Full article