β-Glucan from Saccharomyces cerevisiae has been described to be effective antioxidants, but the specific antioxidation mechanism of β-glucan is unclear. The objectives of this research were to determine whether the β-glucan from Saccharomyces cerevisiae could regulate oxidative stress through the Dectin-1/Nrf2/HO-1 signaling pathway in lipopolysaccharides (LPS)-stimulated RAW264.7 cells. In this study, we examined the effects of β-glucan on the enzyme activity or production of oxidative stress indicators in LPS-stimulated RAW264.7 cells by biochemical analysis and the protein expression of key factors of Dectin-1/Nrf2/HO-1 signaling pathway by immunofluorescence and western blot. The biochemical analysis results showed that β-glucan increased the LPS-induced downregulation of enzyme activity of intracellular heme oxygenase (HO), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) while decreasing the production of reactive oxygen species (ROS) and malondialdehyde (MDA). Furthermore, immunofluorescence results showed that β-glucan can activate the nuclear factor erythroid 2-related factor 2 (Nrf2). The antioxidant mechanism study indicated that β-glucan activated dendritic-cell-associated C-type lectin 1 (Dectin-1) receptors mediated Nrf2/HO-1 signaling pathway, thereby downregulating the production of ROS and thus produced the antioxidant effects in LPS-stimulated RAW 264.7 cells. In conclusion, these results indicate that β-glucan potently alleviated oxidative stress via Dectin-1/Nrf2/HO-1 in LPS-stimulated RAW 264.7 cells.

Liver damage is the most severe complication of heat stress (HS). Hydrolyzed camel whey protein (CWP) possesses bioactive peptides with obviously antioxidant and anti-inflammatory activities. The current study aims to investigate whether CWP that is hydrolyzed by a simulated gastrointestinal digestion process, named S-CWP, protects BRL-3A hepatocytes from HS-induced damage via antioxidant and anti-inflammatory mechanisms. BRL-3A cells were pretreated with S-CWP before being treated at 43 °C for 1 h, and the levels of the cellular oxidative stress, inflammation, apoptosis, biomarkers for liver function, the activities of several antioxidant enzymes, and the cell viability were analyzed. The expression level of pivotal proteins in correlative signaling pathways was evaluated by western blotting. We confirmed that S-CWP alleviated HS-induced hepatocytes oxidative stress by decreased reactive oxygen species (ROS), nitric oxide (NO), 8-Hydroxy-2′-deoxyguanosine (8-OHdG), lipid peroxidation (LPO), protein carbonylation (PCO), and the activities of NADPH oxidase while enhanced superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), heme oxygenase-1 (HO-1) activities, and GSH content. S-CWP suppressed HS-induced inflammatory response by reducing the phosphorylation of NF-κB p65, the expression of NLRP3, and caspase-1 and finally alleviated caspase-3-mediated apoptosis. S-CWP also alleviated HS-induced hepatocyte injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and restoring Heat Shock Protein 70 (HSP70) expression. Furthermore, S-CWP treatment significantly enhanced the expression of NF-E2-related nuclear factor erythroid-2 (Nrf2) and HO-1. The antioxidant and anti-inflammatory effects of S-CWP were weakened by ML385, a specific Nrf2 inhibitor. Additionally, zinc protoporphyrin (ZnPP), a specific HO-1 inhibitor, significantly reversed S-CWP-induced reduction in the phosphorylation of NF-κB p65. Thus, our results revealed that S-CWP protected against HS-induced hepatocytes damage via activating the Nrf2/HO-1 signaling pathway and inhibiting NF-κB/NLRP3 axis.

This study aimed to investigate the mechanism by which camel whey protein (CWP) inhibits the release of high-mobility group box 1 (HMGB1) in heat stress (HS)-stimulated rat liver. Administration of CWP by gavage prior to HS inhibited the cytoplasmic translocation of HMGB1 and consequently reduced the inflammatory response in the rat liver, and downregulated the levels of the NLR pyrin domain containing 3 (NLRP3) inflammasome, interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. The use of N-acetyl-L-cysteine (NAC), an inhibitor of reactive oxygen species (ROS) production, indicated that this downregulation effect may be attributed to the antioxidant activity of CWP. We observed that CWP enhanced nuclear factor erythroid 2-related factor (Nrf)2 and heme-oxygenase (HO)-1 expression, which inhibited ROS production, nicotinamide adenine dinucleotide phosphate oxidase (NOX) activity, and malondialdehyde (MDA) levels, and increased superoxide dismutase 1 (SOD1) activity and reduced glutathione (GSH) content in the HS-treated liver, ultimately increasing the total antioxidant capacity (TAC) in the liver. Administration of Nrf2 or HO-1 inhibitors before HS abolished the protective effects of CWP against oxidative damage in the liver of HS-treated rats, accompanied by increased levels of HMGB1 in the cytoplasm and IL-1β and TNF-α in the serum. In conclusion, our study demonstrated that CWP enhanced the TAC of the rat liver after HS by activating Nrf2/HO-1 signaling, which in turn reduced HMGB1 release from hepatocytes and the subsequent inflammatory response and damage. Furthermore, the combination of CWP and NAC abolished the adverse effects of HS in the rat liver. Therefore, dietary CWP could be an effective adjuvant treatment for HS-induced liver damage.

Camel whey protein (CWP) is a potent natural antioxidant, noted for its abundance of antioxidant amino acids. Despite its promising properties, the precise mechanisms underlying its effects remain inadequately explored. This study aims to investigate the impact of CWP on kidney damage induced by acute heat stress in rats, as well as to elucidate its mechanism of action. We assessed CWP’s influence on cytochrome P450 2J (CYP2J) activity during heat stress, measured oxidative stress levels, and evaluated renal injury using CYP2J knockout rats. Our findings indicate that acute heat stress reduces CYP2J expression, while CWP administration restores CYP2J activity and enhances PI3K/Akt signaling. However, CWP did not mitigate oxidative stress-induced kidney damage in CYP2J^−/− rats, suggesting the necessity of CYP2J for its protective effects.

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.