Abstract Introduction: Type 2 diabetes mellitus (T2DM) is a major global health concern characterized by insulin resistance, hyperglycemia, and chronic inflammation. Interest in natural adjunctive therapies has increased, particularly in mangosteen (Garcinia mangostana), which contains xanthone compounds in the peel with potential antidiabetic properties. Methods: This systematic review followed PRISMA 2020 guidelines. Literature searches were conducted using PubMed, Google Scholar, and ClinicalKey up to December 2022 for studies assessing mangosteen peel extract (MPE) or α-mangostin in diabetic human subjects. Eligible studies included randomized controlled and quasi-experimental trials reporting glycemic or metabolic outcomes. Risk of bias was evaluated using the Cochrane RoB tool. The primary result of this study is to evaluate the effects of mangosteen peel extract supplementation on key glycemic outcomes in patients with T2DM, specifically fasting blood glucose (FBG), HOMA-IR, and HbA1c. Results: A total of two studies (n=2) met the inclusion criteria. A randomized controlled pilot trial reported significant improvement in insulin sensitivity (HOMA-IR −53.2% vs −15.2%; p = 0.004) after 26 weeks of standardized mangosteen extract. A small quasi-experimental study reported a significant reduction in FBG following 7 days of mangosteen peel decoction. Discussion: Limited clinical evidence indicates that mangosteen peel extract may improve insulin sensitivity and lower fasting glucose in T2DM. However, the conclusions are limited by the small number of available studies, the short follow-up duration in one trial, and variability in extract preparation. Conclusion: Mangosteen peel extract demonstrates promising glycemic benefits, including improved insulin sensitivity and reduced fasting glucose. However, the available evidence remains limited by small sample sizes, short follow-up periods, and heterogeneity in extract formulations. Larger randomized controlled trials using standardized preparations are required before clinical recommendations can be made.
Garcinia mangostana ; mangosteen peel extract ; &alpha ; -mangostin ; type 2 diabetes mellitus ; insulin resistance ; oxidative stress

Citrus, which has been consumed internationally for a long time, is widely used as a health food. Citrus and its active components exert significant effects on oxidative stress and lipid metabolism, which are closely associated with female reproductive health. Studies suggest that citrus-derived compounds may alleviate oxidative stress by activating signaling pathways such as nuclear factor erythroid 2-related factor 2 (Nrf2) and Sirtuin 1 (SIRT1), and improve lipid metabolism through the activation of pathways such as peroxisome proliferator-activated receptor α (PPARα). This review focuses on the effects of Citrus on oxidative stress and lipid metabolism, aiming to provide new insights for promoting female reproductive health; however, further work is needed to elucidate the mechanisms involved and validate the therapeutic potential of Citrus's bioactive components in clinical settings.
Citrus/chemistry* ; Oxidative Stress/drug effects* ; Female ; Humans ; Lipid Metabolism/drug effects* ; Reproductive Health ; Animals ; Sirtuin 1/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Signal Transduction/drug effects* ; PPAR alpha/metabolism*

BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

In recent years，with the increase in environmental pollution，organisms are exposed to more internal and external oxidative stress factors than ever before.Nuclear factor erythroid 2-related factor 2（nuclear factor erythroid 2-related factor 2，NRF2），as a core transcription factor in response to oxidative stress，maintains cellular redox homeostasis by inducing the expression of various antioxidant factors.The nasal cavity，as the "gateway" of the respiratory tract，is often accompanied by oxidative stress（oxidative stress，OS）damage，leading to the occurrence of allergic rhinitis（allergic rhinitis，AR）.Recent studies have revealed some associations between the NRF2 signaling pathway and the mechanism of AR development.Activation of NRF2 provides a potential protective effect against AR，and some natural NRF2 activators have shown therapeutic potential in clinical experiments.Therefore，this article briefly reviews the relationship between NRF2 and AR，aiming to provide a new therapeutic target and perspective for the treatment of AR.
NF-E2-Related Factor 2/metabolism* ; Humans ; Rhinitis, Allergic/metabolism* ; Signal Transduction ; Oxidative Stress

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an intracellular transcription factor that helps protect against oxidative stress in different types of cells under pathological conditions. Mitochondria are vital organelles that function in diverse metabolic processes in the body, including redox reactions, lipid metabolism, and cell death. Mitophagy, a specific form of autophagy for damaged mitochondria, plays a critical role in the pathophysiology of liver diseases. In this review, we explain in detail the roles of the Nrf2 signaling pathway and mitophagy, and the relationship between them, in various hepatic diseases (nonalcoholic fatty liver disease, viral hepatitis, alcoholic liver disease, drug-induced liver injury, autoimmune hepatitis, hepatic ischemia‒reperfusion injury, and liver cancer). We also offer some potential insights and treatments relevant to clinical applications.
Humans ; NF-E2-Related Factor 2/metabolism* ; Mitophagy/physiology* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Signal Transduction ; Liver Diseases/etiology* ; Animals ; Oxidative Stress ; Mitochondria/metabolism* ; Non-alcoholic Fatty Liver Disease ; Liver Neoplasms

OBJECTIVES: To explore the effect of quercetin for mitigating HIV-1 gp120-induced astrocyte neurotoxicity and its underlying mechanism. METHODS: Primary rat astrocytes were isolated and treated with quercetin, HIV-1 gp120, or gradient concentrations of quercetin combined with HIV-1 gp120. The formation of stress granules (SGs) in the treated cells was observed with immunofluorescence assay, and the levels of oxidative stress markers and protein expressions were measured using specific assay kits and Western blotting. HIV-1 gp120 transgenic mice were treated with quercetin (50 mg/kg) by gavage for 4 weeks, and the changes in cognitive functions and oxidative stress levels were examined by behavioral assessments, oxidative stress index analysis in serum, and immunohistochemical and Western blotting of the brain tissue. RESULTS: In primary rat astrocytes, treatment with quercetin significantly reduced HIV-1 gp120-induced SG formation, increased the levels of antioxidant indexes, decreased the levels of oxidative substances, and up-regulated protein level associated with SG depolymerization. In the transgenic mouse models, quercetin obviously improved the cognitive function of the rats, reduced oxidative stress levels, and promoted the expression of proteins associate with SG depolymerization in the brain tissues. CONCLUSIONS Quercetin mitigates HIV-1 gp120-induced astrocyte neurotoxicity and cognitive function impairment by inhibiting oxidative stress, enhancing expressions of SG depolymerization-related proteins, and promoting SG disassembly, suggesting the value of quercetin as a potential therapeutic agent for neuroprotection in HIV-associated neurocognitive disorders.
Animals ; Quercetin/pharmacology* ; Astrocytes/metabolism* ; HIV Envelope Protein gp120 ; Oxidative Stress/drug effects* ; Rats ; Stress Granules/drug effects* ; Mice ; Mice, Transgenic ; Rats, Sprague-Dawley ; Cells, Cultured

OBJECTIVES: To investigate the protective effects of dexmedetomidine (DEX) against heat stress (HS)-induced oncosis in human skeletal muscle cells (HSKMCs) and its underlying mechanisms. METHODS: A HSKMC model of HS-induced oncosis were established by 43 ℃ water bath for 4 h, and the effects of treatments with 30 μmol/L DEX, ML385 (a Nrf2 inhibitor) +DEX, si-Nrf2+HS, and si-Nrf2+DEX prior to modeling on cell viability was assessed using CCK-8 assay. Oncosis characteristics were evaluated using transmission electron microscopy and Annexin V-FITC/PI flow cytometry. The oxidative stress markers (GSH, GSH-Px, MDA, SOD and ROS), mitochondrial membrane potential, energy metabolism, and inflammatory cytokines (TNF-α, IL-6 and IL-1β) in the cells were quantified using standard kits, and the expressions of porimin, caspase-3 and Nrf2 pathway proteins were analyzed using Western blotting and qRT-PCR. RESULTS: HS induced typical oncotic features in HSKMCs including organelle swelling and cytoplasmic vacuolization. DEX pretreatment significantly attenuated these changes, reduced Annexin V⁺/PI⁺ cell ratio and cellular porimin expression, and lowered the levels of ROS and MDA while restoring GSH and SOD levels. DEX pretreatment also significantly increased the mitochondrial membrane potential and ATP level, upregulated the expressions of Nrf2, p-Nrf2, HO-1 and NQO1, and suppressed the expressions of TNF-α, IL-6 and IL-1β. The protective effects of DEX were obviously attenuated by interventions with ML385 or si-Nrf2. CONCLUSIONS DEX mitigates HS-induced HSKMC oncosis by activating the Nrf2/HO-1 pathway to relieve oxidative stress, mitochondrial dysfunction, and inflammatory responses.
Humans ; Dexmedetomidine/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Heat-Shock Response/drug effects* ; Signal Transduction/drug effects* ; Membrane Potential, Mitochondrial ; Muscle, Skeletal/cytology* ; Heme Oxygenase-1/metabolism* ; Apoptosis/drug effects*

OBJECTIVES: To explore the role of oxidative stress and immune infiltration in rheumatoid arthritis (RA). METHODS: RA datasets GSE55235 (10 RA vs 10 normal samples) and GSE55457 (13 RA vs 10 normal samples) from the GEO database were merged as the test set to identify the differentially expressed genes (DEGs) in RA using R. The DEGs were intersected with oxidative stress-related genes to obtain oxidative stress-associated DEGs. KEGG and GO enrichment analyses of the DEGs were performed, and the RA-related pathways and biological processes were analyzed using GSEA. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape, and the top 10 key genes were obtained using the Degree algorithm. The validation dataset GSE1919 from GEO database was used for ROC analysis of the key genes to obtain the core genes, and their correlations with infiltrating immune cells were analyzed using CIBERSORT. The results were verified by RT-qPCR for detecting expression levels of the core genes in RA and normal joint samples. RESULTS: We identified 89 oxidative stress-associated DEGs. Enrichment analysis suggested that these DEGs were involved in the biological processes including oxidative stress, chemical stress response, reactive oxygen species response, and lipopolysaccharide response. ROC analysis showed that the 5 core genes (STAT1, MMP9, MYC, CCL5, and JUN) all had AUC values >0.7, indicating their high diagnostic sensitivity and specificity for RA. These genes were closely correlated with immune cells, particularly T cells. RT-qPCR confirmed significant differential expressions of the core genes between RA and normal samples. CONCLUSIONS Oxidative stress and diverse immune responses are features of RA, and the immune responses contribute to activation of oxidative stress. The identified core genes can potential serve as new diagnostic markers for RA.
Arthritis, Rheumatoid/genetics* ; Oxidative Stress/genetics* ; Humans ; Computational Biology ; Protein Interaction Maps ; Gene Expression Profiling ; Gene Regulatory Networks

OBJECTIVES: To explore whether the antioxidant axis Nrf2/HO-1 is involved in the regulation of hippocampus injury induced by cypermethrin and its underlying mechanism. METHODS: Ten-week-old C57BL/6 mice were randomly divided into control group and cypermethrin exposure groups with low, medium, and high exposure levels. After 21 days of oral gavage of corn oil (control) or cypermethrin, the levels of MDA, T-SOD, GSH-Px and CAT in the hippocampus of the mice were examined to evaluate the oxidative stress levels. HE staining was used to observe morphological changes of the hippocampal neurons. Western blotting, immunofluorescence staining and RT-qPCR were employed to detect the protein expressions and mRNA expression of Nrf2 and HO-1 and HO-1. RESULTS: Subacute oral exposure to cypermethrin significantly increased MDA level, decreased the activities of antioxidant enzymes T-SOD, GSH-Px and CAT, and induced neuronal damage in the CA1 and CA3 regions in the hippocampus of C57BL/6 mice. Cypermethrin exposure also caused Nrf2 protein translocation from the cytoplasm to the nucleus, accompanied by upregulated expression levels of the key antioxidant factor Nrf2 and its downstream target kinase HO-1. CONCLUSIONS Cypermethrin exposure dose-dependently causes oxidative damage in the hippocampus of C57BL/6 mice, which is regulated by the Nrf2/HO-1 antioxidant pathway.
Animals ; Pyrethrins/toxicity* ; NF-E2-Related Factor 2/metabolism* ; Hippocampus/cytology* ; Mice, Inbred C57BL ; Mice ; Oxidative Stress/drug effects* ; Neurons/pathology* ; Heme Oxygenase-1/metabolism* ; Signal Transduction ; Membrane Proteins

OBJECTIVES: To investigate the neuroprotective effects of electroacupuncture (EA) preconditioning against cerebral ischemia-reperfusion injury (CIRI) mediated by gut microbiota modulation, Nrf2/HO-1 pathway activation, and ferroptosis suppression. METHODS: Adult male SD rats were divided into sham operation group, CIRI model group, and EA preconditioning group. In the latter two groups, rat models of CIRI were established by middle cerebral artery occlusion (MCAO), and in EA preconditioning group, EA was applied at Baihui (DU20) and Zusanli (ST36) for 3 days before modeling. Neurological deficits, cerebral infarction, and hippocampal pathology of the rats were evaluated using behavioral tests, TTC staining, and Nissl and HE staining, and the oxidative stress markers (MDA, ROS, and SOD), apoptosis/ferroptosis-related proteins (Bax, Bcl-2, GPX4, and SLC7A11), and changes in gut microbiota were analyzed. RESULTS: EA preconditioning significantly reduced neurological deficits, decreased infarct volume, promoted hippocampal neuronal survival, and improved structural integrity of the hippocampal neurons in MCAO rats. EA preconditioning also significantly lowered MDA and ROS and increased SOD levels, upregulated Bcl-2, GPX4, and SLC7A11 expressions, and downregulated Bax expression in the hippocampal tissue of the rats, causing also activation of Nrf2/HO-1 signaling and improvement of gut microbiota composition. CONCLUSIONS EA preconditioning alleviates CIRI in rats by suppressing ferroptosis and apoptosis, enhancing antioxidant defenses via activating Nrf2/HO-1 signaling, and regulating the gut-brain axis.
Animals ; Electroacupuncture ; NF-E2-Related Factor 2/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Reperfusion Injury/therapy* ; Ferroptosis ; Male ; Rats ; Brain Ischemia ; Gastrointestinal Microbiome ; Heme Oxygenase (Decyclizing)/metabolism* ; Brain/metabolism* ; Oxidative Stress ; Heme Oxygenase-1/metabolism* ; Apoptosis