Search Results (89)

Prostate adenocarcinoma (PRAD) poses a significant challenge due to therapy resistance and an immunosuppressive tumor microenvironment (TME). Ferroptosis has emerged as a therapeutic vulnerability, yet its immunomodulatory role in PRAD remains elusive. Here, we employed a multi-omics approach—integrating bulk RNA-seq (498 tumors), single-cell RNA-seq (68,322 cells), and spatial transcriptomics (19,483 spots)—to decode the ferroptosis-immune landscape. We derived a robust 16-gene ferroptosis signature that predicted biochemical recurrence (C-index = 0.76) and validated it in two independent cohorts. Crucially, high-risk tumors exhibited a “cold” immunosuppressive TME enriched in regulatory T cells and M2 macrophages, alongside elevated immune checkpoints (HAVCR2, CTLA4, PDCD1). Single-cell and virtual knockout analyses revealed that cancer epithelial cells evade ferroptosis via NFE2L2-associated antioxidant defenses, which strongly correlates with immune exclusion. Spatial transcriptomics further demonstrated spatially organized vulnerabilities, with ferroptosis-resistant tumor cores and immune-infiltrated invasive margins. To identify therapeutic interventions, we utilized drug response modeling and molecular docking, prioritizing RSL3, Atovaquone (targeting NOX4 (NADPH oxidase 4)/DHODH), and Sorafenib (targeting TrxR1 (thioredoxin reductase 1, encoded by TXNRD1)) as potent agents with potential ferroptosis-modulatory activity. Collectively, our findings demonstrate that NFE2L2-associated ferroptosis resistance shapes immune evasion in PRAD. Targeting ferroptosis regulators provides a compelling therapeutic rationale to remodel the TME and synergize with immune checkpoint blockade. Full article

Background/Objectives: Phillygenin (PHI), a natural lignan derived from Forsythia suspensa, has garnered attention for its potential to alleviate chronic diseases, including chronic colitis, pulmonary fibrosis, and diabetes. Chronic kidney disease (CKD) poses a global health challenge, characterized by high morbidity and mortality rates and associated with a spectrum of secondary complications. In this study, we aim to investigate the therapeutic effectiveness of PHI on CKD and also identify molecular signals by using a unilateral ureteral obstruction (UUO) mouse model and in vitro experiments. Methods: C57BL/6 mice were administered PHI at 50 mg/kg/day to assess its therapeutic effectiveness. In vitro, lipopolysaccharide (LPS) and adenosine triphosphate (ATP) were used to induce pyroptosis, also known as pyroptosis, in renal proximal tubular cells (NRK52E). Results: After PHI treatment for 14 consecutive days, the collagen deposition and extracellular matrix (ECM) accumulation, the expression of oxidative stress response proteins (catalase, superoxide dismutase 2, NADPH oxidase 4, and thioredoxin reductase 1), pro-inflammatory markers (TNF-α and Cyclooxygenase-2(COX-2), and infiltration of neutrophils and macrophages were significantly ameliorated in the UUO mice. Interestingly, the pyroptosis-related proteins (NLRP3/Caspase-1/GSDMD/IL-1β) and cell apoptotic death were also conspicuously relieved after treatment with PHI. Furthermore, PHI administration significantly attenuated the ATP/LPS-induced NF-κB/NLRP3/Caspase-1/GSDMD pyroptosis signal pathway in NRK52E cells. Conclusions: These results demonstrate, for the first time, that PHI treatment ameliorates inflammation and the related pyroptosis via inhibitory regulation of the NF-κB/NLRP3/Caspase-1/GSDMD axis, leading to attenuated renal fibrosis and progressive CKD in UUO mice and in vitro. Our findings suggest that PHI could be a nutraceutical candidate for attenuating CKD progression. Full article

Oxidative stress represents a critical threat to aquatic animal health and aquaculture productivity. Allicin, a natural plant extract, has not been systematically investigated for its antioxidant mechanisms in aquatic crustaceans. This study established in vitro and in vivo models of tert-butyl hydroperoxide (T-BHP)-induced oxidative stress in Chinese mitten crabs (Eriocheir sinensis) to evaluate the hepatoprotective effects of allicin. Integrating biochemical, transcriptomic, and ultrastructural analyses, we found that allicin significantly alleviated T-BHP-induced cytotoxicity and oxidative damage in vitro. Mechanistically, allicin up-regulated antioxidant genes including glutathione peroxidase (gpx) and thioredoxin reductase 1 (trxr1), and down-regulated pro-inflammatory cytokines such as interleukin-1 beta (il-1β), suggesting the concomitant activation of the Nrf2 signaling pathway and inhibition of the p38-MAPK/NF-κB pathway. Transcriptomics further indicated its role in restoring proteostasis and mitochondrial function. A 35-day feeding trial validated these findings in vivo; dietary supplementation with 300 mg·kg⁻¹ allicin effectively reversed T-BHP-induced disturbances in antioxidant enzyme activities and immune-related gene expression. These consistent findings demonstrate that allicin alleviates hepatopancreatic oxidative damage through multi-pathway synergism, supporting its potential as a green and effective antioxidant feed additive in aquaculture. Full article

Chlorobaculum tepidum ferredoxin: ${\mathrm{NADP}}^{+}$ oxidoreductase (CtFNR) is a dimeric thioredoxin reductase (TrxR)-type FNR, whose mechanism and redox properties are poorly characterized. In this work, we focused on the reoxidation mechanisms of its flavin adenine dinucleotide (FAD) cofactor using quinones (Q), nitroaromatics (${\mathrm{ArNO}}_2$), and other nonphysiological oxidants with different single-electron reduction midpoint potentials ($E_7^1$) and electrostatic charge. Like in other FNRs, the rate-limiting step of the reaction is the reoxidation of FAD semiquinone (${\mathrm{FADH}}^{•}$). However, only one FAD per dimer functions in CtFNR due to some nonequivalence of the NADP(H) binding domains in separate subunits. The reactivity of Q increases with increasing $E_7^1$, while ${\mathrm{ArNO}}_2$ form another analogous series of lower reactivity. The compounds are reduced in a dominant single-electron way. These data are consistent with an “outer sphere” electron transfer mechanism. On the basis of reactions with 3-acetylpyridine adenine dinucleotide phosphate, the two-electron reduction midpoint potential of FAD at pH 7.0 is −0.282 V. In CtFNR, 11% ${\mathrm{FADH}}^{•}$ was stabilized at equilibrium. Calculated electron transfer distances in reactions with Q and ${\mathrm{ArNO}}_2$ were in the range of 2.6–3.4 Å. Taken together with previous studies of Rhodopseudomonas palustris and Bacillus subtilis FNRs, this work allows us to generalize the information on the catalytic ant thermodynamic properties of TrxR-type FNRs. In addition, our data may be valuable from an applied perspective, e.g., the use of redox mediators in photobioelectrochemical systems or microbial cells based on anoxygenic phototrophic bacteria. Full article

Auranofin, an FDA-approved antirheumatic drug and thioredoxin reductase 1 (TXNRD1) inhibitor, has demonstrated anti-tumoral properties, but its immunological effects are not well characterized. Here, we report that auranofin unexpectedly promotes regulatory T cell (Treg) expansion. In a B16F10 melanoma model, auranofin treatment increased lung tumor coverage, IL-10 serum levels, and FOXP3⁺CD44⁺CD4⁺ T cell frequencies. It also altered the proportion of antigen-presenting cells (APCs), increasing B cells and reducing dendritic cells. To test whether Treg expansion occurs independently of tumor antigens, we stimulated T cells ex vivo in lymph node cultures from naïve mice using anti-CD3/CD28, with or without auranofin. Auranofin increased Treg frequency in these cultures, as well as in treated human PBMCs. Similar effects were observed with the TXNRD1 inhibitor TRi-1, suggesting a ROS-dependent mechanism. Using mice with conditional expression of neutrophil cytosolic factor 1 (NCF1), we found that both TXNRD1 inhibition and APC-specific NCF1-NOX2-ROS expression enhanced tumor burden and Treg expansion. Alternatively, sorted T cells from mice harboring conditional TXNRD1 knockouts showed reduced FOXP3 and GITR expression in the naïve state and reduced tumor burden when challenged with B16F10. These data suggest TXNRD1 inhibitors likely drive Treg expansion by elevating ROS levels in APCs during T cell priming and less by intrinsic Treg TXNRD1 blockade. Our findings reveal a paradoxical immunosuppressive effect of TXNRD1 inhibitors that may contribute to their limited efficacy in immunocompetent cancer models. This work provides mechanistic insight and underscores the need to consider Treg-mediated immune suppression when designing TXNRD1-targeted therapies. Full article

The antibacterial properties of Ag(I) coordination compounds are well documented; however, their effectiveness is highly dependent on the choice of appropriate ligands, and it is frequently hindered by their low water solubility and limited bioavailability. Herein, six new Ag(I) complexes incorporating the quinazolinone thioamide mqztH (=2-mercapto-4(3H)-quinazolinone) and phosphine co-ligands were synthesized and investigated for their antibacterial activity. In vitro activity assays against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) bacterial strains revealed that all complexes selectively inhibited S. aureus bacterial growth. Structure–activity relationship analysis showed that monodentate PPh₃ co-ligands play a key role in enhancing the antibacterial efficacy of their complexes. Notably, complex [AgCl(mqztH)(PPh₃)₂] (1) exhibited broad-spectrum activity, with IC₅₀ values of 4.2 ± 1.4 μg mL⁻¹ (4.9 μΜ) for S. aureus and 63 ± 1.9 μg mL⁻¹ (75 μΜ) for E. coli bacteria. To improve solubility and antibacterial activity, complex 1 was encapsulated in barium alginate (BaAlg) matrices to form hydrogel-based drug delivery formulations [1]@BaAlg. The synthesized formulations retained the bactericidal effect of the complex, achieving comparable activity at concentrations lower by an order of magnitude compared to complex 1 in free form. Combined with the demonstrated high biocompatibility of complex 1 toward L929 normal eukaryotic cells, as well as the biocompatible nature of the alginate matrix, these findings underscore the strong potential of the complex 1-loaded hydrogel formulations for further investigation and development as effective antibacterial drug platforms. Mechanistic studies confirmed the redox-active nature of complex 1 and its potential to inhibit the function of glutathione reductase (GR) and thioredoxin reductase (TrxR) at low concentrations, suggesting the interference with bacterial redox homeostasis as a relevant mechanism of bioactivity. Full article

Background/Objectives: Selenoproteins play indispensable roles in embryonic development, with their dysregulation linked to various metabolic and neurological disorders. This study aims to systematically quantify the mRNA expression levels of all 24 selenoprotein genes in murine heart, brain, liver, and kidney tissues across embryonic (E8.5, E12.5, E18.5) and postnatal (P7, P30, P90) developmental stages, in order to elucidate the regulatory landscape of selenium metabolism during development. Methods: We collected tissues from mice at six developmental stages and performed RNA extraction followed by quantitative real-time PCR (qPCR) to measure the expression of all 24 selenoprotein genes. Data were normalized using the geometric mean of ActB and Gapdh, and statistical analyses were conducted using one-way ANOVA with Duncan’s post hoc test. Results: Our analysis reveals three principal findings: (1) Distinct expression patterns emerge among selenoprotein families—deiodinases (Dio1-3) and thioredoxin reductases (Txnrd1-3) exhibit limited embryonic expression (<20-fold changes), while glutathione peroxidases (Gpx1, Gpx3, Gpx4) and biosynthesis-related genes (Selenop, Msrb1) show substantial postnatal upregulation (up to 600-fold increases); (2) Selenoproteins essential for embryonic survival (Gpx4, Txnrd1, Txnrd2, Selenoi, Selenot) display expression profiles concordant with their essential developmental functions; (3) Selenop and Msrb1, involved in selenium transport and redox regulation, demonstrate early embryonic upregulation with further increases during postnatal development. Conclusions: These spatiotemporal expression patterns elucidate the regulatory landscape of selenium metabolism during development and provide mechanistic insights into the phenotypes associated with selenium deficiency. The findings offer valuable implications for human nutritional interventions and developmental health. Full article

Selenoprotein thioredoxin reductase 1 (TXNRD1) is frequently upregulated in various cancer cells to sustain cellular redox homeostasis, and its inhibition has emerged as a promising anti-cancer strategy. In this study, we identified PK11007, a thiol-modifying compound previously characterized as a p53 reactivator, as a potent inhibitor of TXNRD1. PK11007 irreversibly inhibited recombinant TXNRD1 in a time- and dose-dependent manner. Using differential scanning fluorimetry (DSF) and LC–MS/MS analysis, we confirmed that PK11007 covalently modifies the C-terminal redox motif (Cys⁴⁹⁷-Sec⁴⁹⁸) of TXNRD1. In non-small cell lung cancer (NSCLC) H1299 cells, PK11007-induced TXNRD1 inhibition disrupted cellular redox balance, leading to impaired autophagy flux and cell death. Similar autophagy suppression was observed in TXNRD1-knockdown cells, as well as pharmacological inhibition of TXNRD1 by Auranofin (AF) and TXNRD1 inhibitor 1 (TRi-1). Taken together, these findings highlight that oxidative stress contributes to the cytotoxic effects of PK11007 and uncover autophagy disorder as a downstream consequence of TXNRD1 inhibition. Full article

CD38, a nicotinamide adenine dinucleotide (NAD⁺) glycohydrolase, increases in old murine macrophages after infection compared to young controls. We aimed to determine whether the increase in CD38 in old murine macrophages after infection is directly associated with enhanced inflammation induced by the oral pathogens Aggregatibacter actinomycetemcomitans (Aa) or Porphyromonas gingivalis (Pg) when compared to young controls. Additionally, we determined the effects of a specific CD38 inhibitor (78c) on CD38, NAD⁺, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α expressions, and anti-oxidative responses in old murine macrophages induced by oral pathogens. Old and young murine macrophages were either uninfected or infected with the oral pathogens Aa or Pg for 1 to 24 h. Protein levels of CD38 and protein kinases, including nuclear factor kappa-B (NF-κB), phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinases (MAPKs), NAD⁺, and inflammatory cytokine (IL-1β, IL-6, TNF-α) levels were evaluated. Additionally, old murine macrophages were treated with a vehicle or a CD38 inhibitor (78c) and cells were either uninfected or infected with Aa or Pg. CD38, NAD⁺, cytokine (IL-1β, IL-6, TNF-α) levels, reactive oxygen species (ROS), NAPDH oxidase 1 (Nox1), and anti-oxidative enzymes, including superoxide dismutase1 (Sod1), glutathione peroxidase 4 (Gpx4), Peroxiredoxin 1 (Prdx1), thioredoxin reductase 1 (Txnrd1), and catalase (Cat), were evaluated. The results showed that old murine macrophages significantly enhanced CD38 and reduced NAD⁺ levels 24 h after Aa or Pg infection compared to young controls. This enhanced CD38 in old murine macrophages was not directly correlated with the activation of protein kinases (NF-κB, PI3K, and MAPKs), nor the (IL-1β, IL-6, TNF-α) levels in macrophages. The inhibition of CD38 by 78c reduced CD38, enhanced NAD⁺ levels, attenuated IL-1β, IL-6 and TNF-α pro-inflammatory cytokine levels, reduced ROS and Nox1 expressions, and enhanced expressions of Sod1, Gpx4, Prdx1, Txnrd1, and Cat in old murine macrophages infected with Aa or Pg. These results suggest that the inhibition of CD38 by 78c is a promising therapeutic strategy to treat aging-associated periodontitis. Full article

Mitoregulin (MTLN) is a 56-amino-acid mitochondrial microprotein known to modulate mitochondrial energetics. MTLN gene expression is elevated broadly across most cancers and has been proposed as a prognostic biomarker for non-small cell lung cancer (NSCLC). In addition, lower MTLN expression in lung adenocarcinoma (LUAD) correlates with significantly improved patient survival. In our studies, we have found that MTLN silencing in A549 NSCLC cells slowed proliferation and, in accordance with this, we observed the following: (1) increased proportion of cells in the G1 phase of cell cycle; (2) protein changes consistent with G1 arrest (e.g., reduced levels and/or reduced phosphorylation of ERK, MYC, CDK2, and RB, and elevated p27^Kip1); (3) reduction in clonogenic cell survival and; (4) lower steady-state cytosolic and mitochondrial H₂O₂ levels as indicated by use of the roGFP2-Orp1 redox sensor. Conflicting with G1 arrest, we observed a boost in cyclin D1 abundance. We also tested MTLN silencing in combination with buthionine sulfoximine (BSO) and auranofin (AF), drugs that inhibit GSH synthesis and thioredoxin reductase, respectively, to elevate the reactive oxygen species (ROS) amount to a toxic range. Interestingly, clonogenic survival after drug treatment was greater for MTLN-silenced cultures versus the control cultures. Lower H₂O₂ output and reduced vulnerability to ROS damage due to G1 status may have jointly contributed to the partial BSO + AF resistance. Overall, our results provide evidence that MTLN fosters H₂O₂ signaling to propel G1/S transition and suggest MTLN silencing as a therapeutic strategy to limit NSCLC growth. Full article

(1) Context: Cancer is still a major problem worldwide, and traditional therapies like radiation and chemotherapy often fail to alleviate symptoms because of side effects, systemic toxicity, and mechanisms of resistance. Beneficial anticancer effects that spare healthy tissues are made possible by the distinctive redox characteristics of noble metal complexes, especially those containing palladium, gold, silver, and platinum. (2) Methods: The redox processes, molecular targets, and therapeutic uses of noble metal complexes in cancer have been the subject of much study over the last 20 years; novel approaches to ligand design, functionalization of nanoparticles, and tumor-specific drug delivery systems are highlighted. (3) Results: Recent developments include Pt(IV) prodrugs and terpyridine-modified Pt complexes for enhanced selectivity and decreased toxicity; platinum complexes, like cisplatin, trigger reactive oxygen species (ROS) production and DNA damage. Functionalized gold nanoparticles (AuNPs) improve targeted delivery and theranostic capabilities, while gold complexes, particularly Au(I) and Au(III), inhibit redox-sensitive processes such as thioredoxin reductase (TrxR). (4) Conclusions: Ag(I)-based compounds and nanoparticles (AgNPs) induce DNA damage and mitochondrial dysfunction by taking advantage of oxidative stress. As redox-based anticancer medicines, noble metal complexes have the ability to transform by taking advantage of certain biochemical features to treat cancer more effectively and selectively. Full article

Background: Selenium and zinc are essential trace elements known to regulate cellular processes including redox homeostasis. During inflammation, circulating selenium and zinc concentrations are reduced in parallel, but underlying mechanisms are unknown. Accordingly, we modulated the zinc and selenium supply of HepG2 cells to study their relationship. Methods: HepG2 cells were supplied with selenite in combination with a short- or long-term zinc treatment to investigate intracellular concentrations of selenium and zinc together with biomarkers describing their status. In addition, the activation of the redox-sensitive transcription factor NRF2 was analyzed. Results: Zinc not only increased the nuclear translocation of NRF2 after 2 to 6 h but also enhanced the intracellular selenium content after 72 h, when the cells were exposed to both trace elements. In parallel, the activity and expression of the selenoprotein thioredoxin reductase 1 (TXNRD1) increased, while the gene expression of other selenoproteins remained unaffected or was even downregulated. The zinc effects on the selenium concentration and TXNRD activity were reduced in cells with stable NRF2 knockdown in comparison to control cells. Conclusions: This indicates a functional role of NRF2 in mediating the zinc/selenium crosstalk and provides an explanation for the observed unidirectional behavior of selenium and zinc. Full article

Glioblastoma (GBM) is an incurable primary brain cancer characterized by increased reactive oxygen species (ROS) production. The redox-sensitive tumor suppressor gene TP53, wild-type (wt) for 70% of patients, regulates redox homeostasis. Glioblastoma stem cells (GSCs) increase thioredoxin (Trx) and glutathione (GSH) antioxidant systems as survival redox-adaptive mechanisms to maintain ROS below the cytotoxic threshold. Auranofin, an FDA-approved anti-rheumatoid drug, inhibits thioredoxin reductase 1 (TrxR1). L-buthionine sulfoximine (L-BSO) and the natural product piperlongumine (PPL) inhibit the GSH system. We evaluated the cytotoxic effects of Auranofin alone and in combination with L-BSO or PPL in GBM cell lines and GSCs with a known TP53 status. The Cancer Genome Atlas/GBM analysis revealed a significant positive correlation between wtp53 and TrxR1 expression in GBM. Auranofin induced ROS-dependent cytotoxicity within a micromolar range in GSCs. Auranofin decreased TrxR1 expression, AKT (Ser-473) phosphorylation, and increased p53, p21, and PARP-1 apoptotic cleavage in wtp53-GSCs, while mutant-p53 was decreased in a mutant-p53 GSC line. Additionally, p53-knockdown in a wtp53-GSC line decreased TrxR1 expression and significantly increased sensitivity to Auranofin, suggesting the role of wtp53 as a negative redox-sensitive mechanism in response to Auranofin in GSCs. The combination of Auranofin and L-BSO synergistically increased ROS, decreased IC50s, and induced long-term cytotoxicity irrespective of p53 in GBM cell lines and GSCs. Intriguingly, Auranofin increased the expression of glutathione S-transferase pi-1 (GSTP-1), a target of PPL. Combining Auranofin with PPL synergistically decreased IC50s to a nanomolar range in GSCs, supporting the potential to repurpose Auranofin and PPL in GBM. Full article

Chinese cabbage (Brassica rapa L. ssp. pekinensis) is an important food crop. However, its growth and development are commonly impacted by black spot disease. To examine the response mechanisms of Chinese cabbage to black spot disease, transcriptome and metabolome sequencing were performed on the leaves of Chinese cabbage genotypes J405 (resistant) and B214 (susceptible), 48 h post-infection (hpi) with Alternaria brassicicola. Expression of essential genes in the jasmonic acid, cytokinin, and auxin signaling pathways of both Chinese cabbage genotypes was inhibited. The expression of the pathogenesis-related protein 1 (PR1) gene mediated by the salicylic acid pathway is inhibited in the Chinese cabbage genotype B214. The basic endochitase B (CHIB) gene in the ethylene pathway of both Chinese cabbage genotypes was upregulated. The accumulation of reactive oxygen species in the disease spots of Chinese cabbage genotype J405 was greater than in genotype B214. The respiratory burst oxidase (RBOH) gene in the reactive oxygen species metabolic pathway was significantly upregulated in genotype J405, while no change was observed in genotype B214. We found that oxidation-reduction-related genes such as type-2 peroxiredoxin genes, NADPH-dependent thioredoxin reductase genes, glutathione peroxidase genes, and glutathione S-transfer genes were differentially expressed across both Chinese cabbage genotypes at 48 hpi. Metabolomics demonstrated that delta-tocopherol and S-hexyl glutathione were all downregulated in genotype J405, while they were upregulated in genotype B214. This approach also identified differential expression of genes in the carotenoid biosynthesis pathway, the glycinebetaine biosynthesis pathway, as well as in the specific sulfur glycoside metabolism pathway. These findings indicate that ethylene signaling is important in the hormone signaling regulatory network-mediated disease resistance and defense in Chinese cabbage. When facing pathogen infection, hormone transduction pathways associated with growth and development in Chinese cabbage are inhibited. The accumulation of reactive oxygen species and the outbreak of various secondary metabolites may endow the Chinese cabbage genotype J405 with increased resistance to black spot disease. Full article

Oxidative stress and inflammation are significant causes of aging. At the same time, citrus flavanones, naringenin (NAR), and hesperetin (HES) are bioactives with proven antioxidant and anti-inflammatory properties. Nevertheless, there are still no data about flavanone’s influence and its potential effects on the healthy aging process and improving pituitary functioning. Thus, using qPCR, immunoblot, histological techniques, and biochemical assays, our study aimed to elucidate how citrus flavanones (15 mg/kg b.m. per os) affect antioxidant defense, inflammation, and stress hormone output in the old rat model. Our results showed that HES restores the redox environment in the pituitary by down-regulating the nuclear factor erythroid 2-related factor 2 (Nrf2) protein while increasing kelch-like ECH-associated protein 1 (Keap1), thioredoxin reductase (TrxR1), and superoxide dismutase 2 (SOD2) protein expression. Immunofluorescent analysis confirmed Nrf2 and Keap1 down- and up-regulation, respectively. Supplementation with NAR increased Keap1, Trxr1, glutathione peroxidase (Gpx), and glutathione reductase (Gr) mRNA expression. Decreased oxidative stress aligned with NLRP3 decrement after both flavanones and glycogen synthase kinase-3 (GSK3) only after HES. The signal intensity of adrenocorticotropic hormone (ACTH) cells did not change, while corticosterone levels in serum decreased after both flavanones. HES showed higher potential than NAR in affecting a redox environment without increasing the inflammatory response, while a decrease in corticosterone level has a solid link to longevity. Our findings suggest that HES could improve and facilitate redox and inflammatory dysregulation in the rat’s old pituitary. Full article