Search Results (1,133)

Cisplatin remains a cornerstone chemotherapeutic agent; however, its off-target gonadotoxicity poses a significant risk for premature ovarian failure (POF) and infertility in young women. Strategies to preserve ovarian function during chemotherapy are critically needed. To investigate the protective effects of krill oil supplementation against cisplatin-induced ovarian damage in a rat model, with a focus on oxidative stress, inflammation, follicular dynamics, and stromal fibrosis. Twenty-one adult female Wistar albino rats were randomized into three groups: control, cisplatin-treated, and cisplatin + krill oil-treated. Ovarian toxicity was induced via intraperitoneal injection of cisplatin (2.5 mg/kg, twice weekly for four weeks). Krill oil (4 mL/kg/day) was administered orally during the same period. Ovarian histopathology, follicle counts (primordial, primary, secondary, tertiary), stromal fibrosis, and biochemical markers, including plasma anti-Müllerian hormone (AMH), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and ovarian levels of nuclear factor erythroid 2-related factor 2 (Nrf2), Toll-like receptor 4 (TLR4), TNF-α, NOD-like receptor family pyrin domain containing 3 (NLRP3), and IL-1β were evaluated. Cisplatin significantly reduced primordial, primary, secondary, and tertiary follicle counts while increasing stromal fibrosis (p < 0.001). Krill oil co-treatment notably ameliorated follicular depletion—improving follicle counts by 38.16%, 54.74%, 62.5%, 40.43%, respectively—and reduced fibrosis (p = 0.017). Biochemically, cisplatin decreased AMH levels and Nrf2 expression while elevating MDA, TNF-α, TLR4, NLRP3, and IL-1β levels (p < 0.001). Krill oil supplementation restored AMH (p = 0.002) and Nrf2 (p = 0.003) levels, while reducing MDA (p = 0.009), NLRP3 (p < 0.001), ovarian IL-1β (p = 0.005), plasma IL-1β (p < 0.001), TLR4 (p = 0.001), plasma TNF-α (p = 0.001), and ovarian TNF-α (p < 0.001), compared to the cisplatin group. Krill oil exerts significant antioxidant and anti-inflammatory effects, offering a promising strategy to mitigate cisplatin-induced ovarian damage and preserve fertility in young cancer patients. Full article

Curcumin, the principal active component of turmeric, is a polyphenol that has been used in various countries for the treatment of numerous conditions due to its wide range of health benefits. Curcumin exhibits bifunctional antioxidant properties: the first is attributed to its chemical structure, which enables it to directly neutralize reactive oxygen species (ROS); the second is related to its ability to induce the expression of antioxidant enzymes via the transcription factor nuclear factor erythroid 2–related factor 2 (Nrf2). Both ROS and Nrf2 are closely associated with mitochondrial function and metabolism, and their dysregulation may lead to mitochondrial dysfunction, potentially contributing to the development of various pathological conditions. Therefore, curcumin treatment appears highly promising and is strongly associated with the preservation of mitochondrial function. The aim of this review is to summarize the current literature on the impact of curcumin’s antioxidant properties on mitochondrial function. Specifically, studies conducted in different biological models are included, with emphasis on aspects such as mitochondrial respiration, antioxidant enzyme activity, interactions with mitochondrial membranes, and the role of curcumin in the regulation of intrinsic apoptosis. Full article

Redox balance is essential for maintenance of the hematopoietic stem cell (HSC) pool, which ensures the lifelong hematopoiesis. However, oxidative attack induced by various physiopathological stresses always compromises HSC maintenance, while there remains lack of safe and effective antioxidative measures combating these conditions. Here, we show that ferulic acid (FA), a natural antioxidant abundantly present in Angelica sinensis which is a traditional Chinese herb commonly used for promotion of blood production, distinctively and directly promotes HSC maintenance and thereby boosts hematopoiesis at homeostasis, whether supplemented over the long term in vivo or in HSC culture ex vivo. Using a mouse model of acute myelosuppressive injury induced by ionizing radiation, we further reveal that FA supplementation effectively safeguards HSC maintenance and accelerates hematopoietic regeneration after acute myelosuppressive injury. Mechanistically, FA diminishes ferroptosis susceptibility of HSCs through limiting the labile iron pool (LIP), thus favoring HSC maintenance. In addition, the LIP limitation and anti-ferroptosis activity of FA is independent of nuclear-factor erythroid 2-related factor 2 (NRF2), probably relying on its iron-chelating ability. These findings not only uncover a novel pharmacological action and mechanism of FA in promoting HSC maintenance, but also provides a therapeutic rationale for using FA or FA-rich herbs to treat iron overload- and ferroptosis-associated pathologies such as acute myelosuppressive injury. Full article

Oxidative stress is the key contributor to the onset of numerous diseases. Herein, we develop tea polyphenol–zinc (Tp-Zn) using a metal–polyphenol coordination strategy through a simple hybrid approach. The product is characterized by methods such as dynamic light scattering (DLS), ultraviolet–visible spectroscopy (UV–vis) and transmission electron microscopy (TEM) to evaluate the particle size and potential of Tp-Zn. Oxidative stress was induced in mice by administering diquat (25 mg/kg body weight) followed by pre-treatment with 210 mg/kg body weight tea polyphenols (TPs), 280 mg/kg body weight Tp-Zn, and 70 mg/kg body weight ZnSO₄ for 7 days. Results showed that Tp-Zn treatment significantly improved intestinal barrier function by preventing the diquat-induced down-regulation of tight junction proteins Zonula Occludens protein 1 (ZO-1) and occludin. It also mitigated liver inflammation and damage, as evidenced by reduced serum levels of Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and Alkaline phosphatase (AKP). Furthermore, Tp-Zn enhanced the antioxidant response in both the intestine and liver by up-regulating the mRNA expression of antioxidant enzymes and reducing the levels of Malondialdehyde (MDA) and reactive oxygen species (ROS) compared to the diquat group (DIQ group). Also, the detection of ROS in the small intestine confirmed Tp-Zn markedly increased intestinal Nuclear factor erythroid 2-related factor 2 (Nrf2) expression compared to the control group. This study aims to clarify that metal–polyphenol coordination with multifaceted regulation of the inflammatory microenvironment could be a novel approach for preventing or treating oxidative stress-related diseases. Full article

Nuclear factor erythroid 2-related factor 2 (NRF2) serves as a master transcriptional regulator of cellular antioxidant responses through orchestration of cytoprotective gene expression, establishing its significance as a therapeutic target in cerebral pathophysiology. Classical electrophilic NRF2 activators, despite potent activation potential, exhibit paradoxically reduced therapeutic efficacy relative to single antioxidants, attributable to concurrent oxidative stress generation, glutathione depletion, mitochondrial impairment, and systemic toxicity. Although emerging non-electrophilic pharmacological activators offer therapeutic potential, their utility remains limited by bioavailability and suboptimal potency, underscoring the imperative for innovative therapeutic strategies to harness this cytoprotective pathway. Non-pharmacological interventions, including neuromodulation, physical exercise, and lifestyle modifications, activate NRF2 through non-canonical, non-electrophilic pathways involving protein–protein interaction inhibition, KEAP1 degradation, post-translational and transcriptional modulation, and protein stabilization, though mechanistic characterization remains incomplete. Such interventions utilize multi-mechanistic approaches that synergistically integrate multiple non-electrophilic NRF2 pathways or judiciously combine electrophilic and non-electrophilic mechanisms while mitigating electrophile-induced toxicity. This strategy confers neuroprotective effects without the contraindications characteristic of classical electrophilic activators. This review comprehensively examines the mechanistic underpinnings of non-pharmacological NRF2 modulation, highlighting non-electrophilic activation pathways that bypass the limitations inherent to electrophilic activators. The evidence presented herein positions non-pharmacological interventions as viable therapeutic approaches for achieving non-electrophilic NRF2 activation in the treatment of cerebrovascular and neurodegenerative pathologies. Full article

This review aims to provide a comprehensive overview of how oxidative stress drives inflammation, structural remodeling, and clinical expression of childhood asthma, while critically appraising emerging redox-sensitive biomarkers and antioxidant-focused preventive and therapeutic strategies. Oxidative stress arises when reactive oxygen species (ROS) and reactive nitrogen species (RNS) outpace airway defenses. This surplus provokes airway inflammation: ROS/RNS activate nuclear factor kappa-B (NF-κB) and activator protein-1 (AP-1), recruit eosinophils and neutrophils, and amplify type-2 cytokines. Normally, an antioxidant network—glutathione (GSH), enzymes such as catalase (CAT) and superoxide dismutase (SOD), and nuclear factor erythroid 2-related factor 2 (Nrf2)—maintains redox balance. Prenatal and early exposure to fine particulate matter <2.5 micrometers (µm) (PM_2.5), aeroallergens, and tobacco smoke, together with polymorphisms in glutathione S-transferase P1 (GSTP1) and CAT, overwhelm these defenses, driving epithelial damage, airway remodeling, and corticosteroid resistance—the core of childhood asthma pathogenesis. Clinically, biomarkers such as exhaled 8-isoprostane, hydrogen peroxide (H₂O₂), and fractional exhaled nitric oxide (FeNO) surge during exacerbations and predict relapses. Therapeutic avenues include Mediterranean-style diet, regular aerobic exercise, pharmacological Nrf2 activators, GSH precursors, and mitochondria-targeted antioxidants; early trials report improved lung function and fewer attacks. Ongoing translational research remains imperative to substantiate these approaches and to enable the personalization of therapy through individual redox status and genetic susceptibility, ultimately transforming the care and prognosis of pediatric asthma. Full article

This study investigated the hepatoprotective effects of cinnamic acid (CA) against liver injury and fat accumulation induced by a high-fat diet (HFD), focusing on the role of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Male Wistar rats were divided into six groups: a control group receiving carboxymethylcellulose; a CA control group (40 mg/kg); an HFD group; two HFD groups treated with CA (20 mg/kg or 40 mg/kg); and a HFD group co-treated with CA (40 mg/kg) and brusatol (2 mg/kg, i.p.), a selective Nrf2 inhibitor. CA was administered orally, and brusatol intraperitoneally, both twice per week for twelve weeks. CA had no effect on serum glucose or insulin but improved serum and hepatic profiles in HFD rats. It also attenuated liver vacuolization and normalized serum levels of ALT, AST, and γ-GT. CA also reduced hepatic apoptosis by increasing Bcl2 and reducing Bax and caspase-3 levels. CA mitigated oxidative stress by reducing MDA and enhancing SOD and GSH levels. It suppressed inflammatory mediators, including TNF-α, IL-6, and NF-κB. CA also downregulated SREBP1, FAS, ACC-1, and Keap1 while increasing mRNA and nuclear translocation of Nrf2. All these effects were dose-dependent. Similar molecular effects of CA were also seen in control rats while CA protection in HFD rats was abolished with brusatol indicating Nrf2-dependency. Such findings highlight CA as a promising nutraceutical candidate for preventing HFD-induced liver injury. Further studies are warranted to explore its clinical applicability in metabolic liver diseases. Full article

Chlorpyrifos (CPF), an organophosphate pesticide, is known to induce pulmonary toxicity through oxidative stress, mitochondrial dysfunction, and inflammation. Astaxanthin (ASX), a xanthophyll carotenoid derived primarily from marine microalgae (Haematococcus pluvialis), possesses strong antioxidant properties and has demonstrated cellular protective effects in numerous oxidative stress studies. However, its efficacy against CPF-induced lung cell damage remains uncharacterized. This study revealed the protective role of ASX, as a pretreatment and co-treatment, against CPF-induced cytotoxicity in human A549 lung adenocarcinoma cells by assessing cell viability, intracellular reactive oxygen species (IROS), total oxidative status (TOS), total antioxidant capacity (TAC), mitochondrial membrane potential (MMP), intracellular calcium ions (Ca²⁺), lactate dehydrogenase (LDH) release, malondialdehyde (MDA) levels, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, DNA fragmentation, and apoptosis/inflammation-associated gene expression. CPF treatment significantly decreased cell viability and TAC, while elevating IROS, TOS, MMP, intracellular Ca²⁺, and LDH release. CPF also increased MDA levels and suppressed GPx and SOD activities. DNA fragmentation and quantitative polymerase chain reaction (qPCR) analysis revealed upregulation of pro-apoptotic and inflammatory markers such as BCL2-associated X protein (BAX), caspase-3 (CASP3), tumor protein p53 (TP53), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor kappa B (NFκB), and voltage-dependent anion-selective channel protein 1 (VDAC1) and suppression of anti-apoptotic B-cell lymphoma 2 (BCL2) and antioxidant defense genes nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). ASX treatment, particularly when administered as a pretreatment, significantly reversed CPF-induced oxidative and inflammatory responses by restoring SOD, GPx, and TAC levels, reducing IROS, TOS, MDA, and LDH release, and downregulating apoptotic and inflammatory gene expressions. ASX pretreatment notably decreased MMP and intracellular Ca²⁺ levels, indicating protection against mitochondrial dysfunction and calcium dysregulation. ASX upregulated Nrf2 and HO-1 expression and restored the BCL2/BAX balance, suggesting inhibition of mitochondrial-mediated apoptosis. Additionally, ASX significantly attenuated CPF-induced anti-angiogenic effects in the in ovo Hen’s Egg Test Chorioallantoic Membrane (HET-CAM) assay. These findings demonstrate, for the first time, that ASX exerts a broad spectrum of protective effects against CPF-induced cytotoxicity in lung cells, mainly through the stabilization of mitochondrial redox status and modulation of apoptosis- and inflammation-related gene pathways, highlighting ASX as a promising candidate for further therapeutic development. Furthermore, the pronounced efficacy observed in the pretreatment regimen suggests that ASX can be evaluated as a potential nutritional preventive strategy in high-risk populations with occupational or environmental CPF exposure. Full article

Geographic atrophy or late-stage dry age-related macular degeneration (AMD) is characterized by drusen deposition and progressive retinal pigment epithelium (RPE) degeneration, leading to irreversible vision loss. The formation of drusen leads to dyshomeostasis, oxidative stress, and irreversible damage to the RPE. In this study, we used an in vitro model of oxidized low-density lipoprotein (ox-LDL)-induced human RPE damage/death to investigate the mechanism through which a sterically hindered phenol antioxidant compound, PMC (2,2,5,7,8-pentamethyl-6-chromanol), protects the RPE against ox-LDL-induced damage. We show that PMC exerts its protective effect by preventing the upregulation of stress-responsive heme oxygenase-1 (HMOX1/HO-1) and NAD(P)H: quinone oxidoreductase (NQO1) at the mRNA and protein levels. This effect was due to PMC’s blockade of ROS generation, which in turn blocked nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, ultimately preventing the upregulation of antioxidant response elements (AREs), including HMOX1 and NQO1. The key role of HO-1 was demonstrated when the protective effect of PMC was inhibited by the knockdown of HMOX1. Additionally, PMC treatment under different experimental conditions and at different time points revealed that the continuous presence of PMC is required for the optimal protection against ox-LDL-induced cytotoxicity, defining the cellular pharmacokinetics of this molecule. Our data demonstrate the involvement of a key antioxidant pathway through which PMC mitigates the oxidative stress induced by ox-LDL and provides a potential therapeutic strategy for suppressing RPE degeneration/damage during AMD progression. Full article

Ferroptosis is an iron-dependent form of regulated cell death marked by lipid peroxidation in polyunsaturated phospholipids. In head and neck cancer (HNC), where resistance to chemotherapy and immunotherapy is common, ferroptosis offers a mechanistically distinct strategy to overcome therapeutic failure. However, cancer cells often evade ferroptosis via activation of nuclear factor erythroid 2-related factor 2 (Nrf2), a key regulator of antioxidant and iron-regulatory genes. HNC remains therapeutically challenging due to therapy resistance driven by redox adaptation. This review highlights the ferroptosis pathway—a form of regulated necrosis driven by iron and lipid peroxidation—and its regulation by Nrf2, a master antioxidant transcription factor. We detail how Nrf2 contributes to ferroptosis evasion in HNC and summarize emerging preclinical studies targeting this axis. The review aims to synthesize molecular insights and propose therapeutic perspectives for overcoming resistance in HNC by modulating Nrf2–ferroptosis signaling. We conducted a structured narrative review of the literature using PubMed databases. Relevant studies from 2015 to 2025 focusing on ferroptosis, Nrf2 signaling, and head and neck cancer were selected based on their experimental design, novelty, and relevance to clinical resistance mechanisms. In HNC, Nrf2 mediates resistance through transcriptional upregulation of GPX4 and SLC7A11, epigenetic stabilization by PRMT4 and ALKBH5, and activation by FGF5 and platelet-derived extracellular vesicles. Epstein–Barr virus (EBV) infection also enhances Nrf2 signaling in nasopharyngeal carcinoma. More recently, loss-of-function KEAP1 mutations have been linked to persistent Nrf2 activation and upregulation of NQO1, which confer resistance to both ferroptosis and immune checkpoint therapy. Targeting NQO1 in KEAP1-deficient models restores ferroptosis and reactivates antitumor immunity. Additionally, the natural alkaloid trigonelline has shown promise in reversing Nrf2-mediated ferroptosis resistance in cisplatin-refractory tumors. Pharmacologic agents such as auranofin, fucoxanthin, carnosic acid, and disulfiram/copper complexes have demonstrated efficacy in sensitizing HNC to ferroptosis by disrupting the Nrf2 axis. This review summarizes emerging mechanisms of ferroptosis evasion and highlights therapeutic strategies targeting the Nrf2–ferroptosis network. Integrating ferroptosis inducers with immune and chemotherapeutic approaches may provide new opportunities for overcoming resistance in head and neck malignancies. Full article

Although chemotherapy is the preferred treatment for gastric cancer, the therapeutic drugs currently available have limited efficacy and severe side effects. Cancer stem cells within tumor masses have the distinctive properties of self-renewal, maintenance, and resistance to chemotherapy. Hence, agents capable of targeting stemness in gastric tumors with minimal side effects are urgently required. Enzymes that generate reactive oxygen species contribute to the high oxidation levels observed in tumors. Additionally, nuclear factor erythroid 2-related factor 2 (Nrf2), an antioxidant transcription factor, regulates cancer stemness. Increasing evidence highlights the potential of nutritional supplementation to treat cancer stemness. ω-3 polyunsaturated fatty acids support human health and offer benefits for cancer treatment. Linolenic acid (LA), an ω-3 polyunsaturated fatty acid, inhibits the expression of proteins associated with stemness and promotes apoptosis in gastric cancer cells. Our findings indicated that LA treatment substantially inhibited key characteristics of gastric cancer stemness and induced oxidative stress and caspase-3-mediated apoptosis by downregulating Nrf2-mediated expression. These results suggest that LA is a promising nutritional supplement for targeting cancer stemness in the treatment of gastric cancer. Full article

Ionizing radiation (IR) as a stress inducer has a significant impact on various normal stem cells differentiation through activation of various signaling pathways. Low levels of oxidative stress of IR may preserve or even enhance cell differentiation. In response to IR, reactive oxygen species (ROS) can activate various signaling pathways that promote cell differentiation, notably through the involvement of nuclear factor erythroid 2–related factor 2 (NRF2). NRF2 interacts with multiple pathways, including Wnt/β-catenin (osteogenesis), PPARγ (adipogenesis), and BDNF/TrkB (neurogenesis). This response is dose-dependent: low doses of IR activate NRF2 and support differentiation, while high doses can overwhelm the antioxidant system, resulting in cell death. However, the quality of various types of IR, such as proton and carbon ion radiation, may have a varied impact on stem cells (SCs) differentiation compared to X-rays. Hence, activation of the NRF2 signaling pathway in SCs and cell differentiation depends on the level of stress and the quality and quantity of IR. This review is an update to explore how IR modulates SCs fate toward osteogenic, adipogenic, and neurogenic lineages through the NRF2 signaling pathway. We highlight mechanistic insights, dose-dependent effects, and therapeutic implications, bridging gaps between experimental models and clinical translation. Full article

Doxorubicin (Dox) is a potent anthracycline antitumor drug whose clinical utility is significantly restricted by its dose-dependent, cumulative cardiotoxicity, driven by increased oxidative stress, impaired antioxidant defenses, and apoptosis-mediated cardiomyocyte loss. Methylene blue (MB), a phenothiazine derivative with well-documented redox-modulating properties, is being explored as a viable cardioprotective agent due to its antioxidant and anti-apoptotic effects. This study evaluated the protective role of MB against Dox-induced cardiotoxicity in rats by examining its impact on oxidative stress markers (Kelch-like ECH-associated protein 1; KEAP1, nuclear factor erythroid 2-related factor 2; NRF2, Glutathione peroxidase 4; GPX-4, 8-hydroxy-2′-deoxyguanosine; 8-OHdG), neurohormonal indicators (noradrenaline), cardiac injury biomarkers (troponin I), and apoptotic mediators (p53, Caspase-3). Forty male albino rats were divided equally into four groups: control, Dox (15 mg/kg, i.p.), MB alone (4 mg/kg/day, p.o. for 7 days), and Dox plus MB. Dox administration significantly increased serum troponin I and noradrenaline levels, elevated cardiac KEAP1 and 8-OHdG, and reduced NFE2L2, NRF2, and GPX-4 expression. It also upregulated p53 and Caspase-3 and caused marked myocardial degeneration, necrosis, and inflammatory infiltration. MB co-treatment significantly reduced troponin I and noradrenaline levels, restored KEAP1/NFE2L2 (NRF2)/GPX-4 pathway balance, decreased oxidative DNA damage, and attenuated p53 and Caspase-3 activation, preserving myocardial architecture with minimal inflammatory changes. These findings demonstrate that MB confers potent cardioprotection against Dox-induced cardiac injury by enhancing antioxidant defenses, limiting oxidative DNA damage, suppressing apoptosis, and normalizing neurohormonal imbalance, suggesting its promise as an adjunctive strategy to mitigate anthracycline-associated cardiotoxicity. Full article

Urolithin (Uro)-B, a gut microbiota metabolite of ellagic acid, has recently gained considerable attention due to its beneficial bioactivities. This study investigated the potential hepatoprotective effect of Uro-B against alpha-naphthyl isothiocyanate (ANIT)-induced cholestatic liver injury (CLI) in mice and explored the possible involved mechanisms. Mice were treated with Uro-B (50 and 100 mg/kg) for four days and received ANIT (75 mg/kg) once on the second day. Our data revealed that Uro-B reduced elevated serum transaminases, alkaline phosphatase, lactate dehydrogenase, and total bilirubin levels associated with ANIT injection. Histopathologically, Uro-B effectively ameliorated ANIT-induced disruption of the hepatic architecture as represented by repressed necro-inflammation and bile duct proliferation. Uro-B also maintained oxidant/antioxidant status that was dysregulated by ANIT. Mechanistically, Uro-B markedly activated Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling with subsequent upregulation of hepatic heme oxygenase-1 expression. On the other hand, Uro-B suppressed the ANIT-induced expression of nuclear factor kappa-B (NF-κB), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Interestingly, Uro-B repressed peroxisome proliferator-activated receptor alpha (PPARα) expression in the liver. These findings indicate a promising hepatoprotective effect of Uro-B against ANIT-induced CLI in mice. Uro-B modulated the interplay between Keap1/Nrf2, NF-κB/TNF-α, and PPARα signaling pathways, resulting in powerful antioxidant and anti-inflammatory effects. Full article

Heat stress (HS) is known to cause liver injury through mechanisms involving oxidative stress and inflammation, thereby highlighting the need for effective therapeutic interventions. This study evaluated the efficacy of sprouted black quinoa extract (SBQE) in mitigating HS-induced liver injury in a rat model. SBQE was obtained through an ultrasonication-assisted ethanol–water extraction process from black quinoa germinated for 48 h. Sprague Dawley rats (male) were administered via oral gavage SBQE at doses of 200, 400, or 800 mg/kg prior to each HS exposure (40 °C for 2 h per day over a period of 8 days). Pretreatment with SBQE resulted in a dose-dependent reduction in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, with the high dose (800 mg/kg) reducing these enzyme levels (p < 0.001 vs. HS group) and alleviating histopathological damage, including a significant decrease in hepatocyte vacuolization and inflammatory cell infiltration (histopathological scores were reduced by p < 0.001 in the 800 mg/kg SBQE group vs. HS group). SBQE also dose-dependently inhibited the accumulation of mitochondrial reactive oxygen species (mean fluorescence intensity decreased by p < 0.001 at 800 mg/kg) and the formation of malondialdehyde while restoring the activities of antioxidant enzymes such as superoxide dismutase (p < 0.01 at 800 mg/kg), catalase (p < 0.05 at 800 mg/kg), and glutathione peroxidase (p < 0.001 at 800 mg/kg), as well as replenishing glutathione levels (p < 0.001 at 800 mg/kg). Furthermore, the levels of proinflammatory cytokines (tumor necrosis factor-alpha, interleukin-6, interleukin-1β, and interleukin-18) in liver tissue were significantly reduced (with the high dose leading to p < 0.001 vs. HS group), which was associated with enhanced nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2; p < 0.05 at 800 mg/kg) and decreased phosphorylation of nuclear factor-κB p65 (NF-κB; p < 0.001 at 800 mg/kg). Additionally, the protein expression of NOD-like receptor pyrin domain-containing 3 (NLRP3) inflammasome components and markers of apoptosis were diminished. The results demonstrated that SBQE alleviated HS-induced liver injury by concurrently activating the Nrf2 antioxidant pathway and suppressing NF-κB/NLRP3 inflammasome signaling, suggesting its potential as a nutraceutical intervention for HS-related hepatotoxicity. Full article