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Search Results (1,498)

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Keywords = Nrf2 antioxidative pathway

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26 pages, 1030 KiB  
Review
Natural Flavonoids for the Prevention of Sarcopenia: Therapeutic Potential and Mechanisms
by Ye Eun Yoon, Seong Hun Ju, Yebean Kim and Sung-Joon Lee
Int. J. Mol. Sci. 2025, 26(15), 7458; https://doi.org/10.3390/ijms26157458 (registering DOI) - 1 Aug 2025
Abstract
Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for [...] Read more.
Sarcopenia, characterized by progressive skeletal muscle loss and functional decline, represents a major public heath challenge in aging populations. Despite increasing awareness, current management strategies—primarily resistance exercise and nutritional support—remain limited by accessibility, adherence, and inconsistent outcomes. This underscores the urgent need for novel, effective, and scalable therapeutics. Flavonoids, a diverse class of plant-derived polyphenolic compounds, have attracted attention for their muti-targeted biological activities, including anti-inflammatory, antioxidant, metabolic, and myogenic effects. This review aims to evaluate the anti-sarcopenic potential of selected flavonoids—quercetin, rutin, kaempferol glycosides, baicalin, genkwanin, isoschaftoside, naringin, eriocitrin, and puerarin—based on recent preclinical findings and mechanistic insights. These compounds modulate key pathways involved in muscle homeostasis, such as NF-κB and Nrf2 signaling, AMPK and PI3K/Akt activation, mitochondrial biogenesis, proteosomal degradation, and satellite cell function. Importantly, since muscle wasting also features prominently in cancer cachexia—a distinct but overlapping syndrome—understanding flavonoid action may offer broader therapeutic relevance. By targeting shared molecular axes, flavonoids may provide a promising, biologically grounded approach to mitigating sarcopenia and the related muscle-wasting conditions. Further translational studies and clinical trials are warranted to assess their efficacy and safety in human populations. Full article
(This article belongs to the Special Issue Role of Natural Products in Human Health and Disease)
32 pages, 2108 KiB  
Review
Phytochemical Composition and Multifunctional Applications of Ricinus communis L.: Insights into Therapeutic, Pharmacological, and Industrial Potential
by Tokologo Prudence Ramothloa, Nqobile Monate Mkolo, Mmei Cheryl Motshudi, Mukhethwa Michael Mphephu, Mmamudi Anna Makhafola and Clarissa Marcelle Naidoo
Molecules 2025, 30(15), 3214; https://doi.org/10.3390/molecules30153214 (registering DOI) - 31 Jul 2025
Abstract
Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its [...] Read more.
Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its terminal panicle-like inflorescences bear monoecious flowers, and its seeds are enclosed in prickly capsules. Throughout its various parts, R. communis harbours a diverse array of bioactive compounds. Leaves contain tannins, which exhibit astringent and antimicrobial properties, and alkaloids like ricinine, known for anti-inflammatory properties, as well as flavonoids like rutin, offering antioxidant and antibacterial properties. Roots contain ellagitannins, lupeol, and indole-3-acetic acid, known for anti-inflammatory and liver-protective effects. Seeds are renowned for ricin, ricinine, and phenolic compounds crucial for industrial applications such as biodegradable polymers. Pharmacologically, it demonstrates antioxidant effects from flavonoids and tannins, confirmed through minimum inhibitory concentration (MIC) assays for antibacterial activity. It shows potential in managing diabetes via insulin signalling pathways and exhibits anti-inflammatory properties by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, it has anti-fertility effects and potential anticancer activity against cancer stem cells. This review aims to summarize Ricinus communis’s botanical properties, therapeutic uses, chemical composition, pharmacological effects, and industrial applications. Integrating the current knowledge offers insights into future research directions, emphasizing the plant’s diverse roles in agriculture, medicine, and industry. Full article
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17 pages, 1485 KiB  
Article
Selective Inhibition of Vascular Smooth Muscle Cell Function by COVID-19 Antiviral Drugs: Impact of Heme Oxygenase-1
by Kelly J. Peyton, Giovanna L. Durante and William Durante
Antioxidants 2025, 14(8), 945; https://doi.org/10.3390/antiox14080945 (registering DOI) - 31 Jul 2025
Abstract
Coronavirus disease 2019 (COVID-19) causes cardiovascular complications, which contributes to the high mortality rate of the disease. Emerging evidence indicates that aberrant vascular smooth muscle cell (SMC) function is a key driver of vascular disease in COVID-19. While antivirals alleviate the symptoms of [...] Read more.
Coronavirus disease 2019 (COVID-19) causes cardiovascular complications, which contributes to the high mortality rate of the disease. Emerging evidence indicates that aberrant vascular smooth muscle cell (SMC) function is a key driver of vascular disease in COVID-19. While antivirals alleviate the symptoms of COVID-19, it is not known whether these drugs directly affect SMCs. Accordingly, the present study investigated the ability of three approved COVID-19 antiviral drugs to influence SMC function. Treatment of SMCs with remdesivir (RDV), but not molnupiravir or nirmatrelvir, inhibited cell proliferation, DNA synthesis, and migration without affecting cell viability. RDV also stimulated an increase in heme oxygenase-1 (HO-1) expression that was not observed with molnupiravir or nirmatrelvir. The induction of HO-1 by RDV was abolished by mutating the antioxidant responsive element of the promoter, overexpressing dominant-negative NF-E2-related factor-2 (Nrf2), or treating cells with an antioxidant. Finally, silencing HO-1 partly rescued the proliferative and migratory response of RDV-treated SMCs, and this was reversed by carbon monoxide and bilirubin. In conclusion, the induction of HO-1 via the oxidant-sensitive Nrf2 signaling pathway contributes to the antiproliferative and antimigratory actions of RDV by generating carbon monoxide and bilirubin. These pleiotropic actions of RDV may prevent occlusive vascular disease in COVID-19. Full article
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17 pages, 1160 KiB  
Article
Enhanced Antioxidant and Antiproliferative Activities of Apple and Korean Green Chili Pepper Extracts Cultivated with Mineral Supplementation
by Ji-Sun Lim, Mi-Hee Yu, Dong Kyu Choi, Hae Won Kim, Seung-Hwan Park, Sin-Il Sin and Jong-Sang Kim
Foods 2025, 14(15), 2685; https://doi.org/10.3390/foods14152685 - 30 Jul 2025
Abstract
Apples and Korean green chili peppers are rich in phytochemicals and recognized for their diverse bioactive properties. Given the potential to enhance these beneficial compounds, this study investigated the effects of mineral supplementation during cultivation on the antioxidant and antiproliferative activities of extracts [...] Read more.
Apples and Korean green chili peppers are rich in phytochemicals and recognized for their diverse bioactive properties. Given the potential to enhance these beneficial compounds, this study investigated the effects of mineral supplementation during cultivation on the antioxidant and antiproliferative activities of extracts from both crops. Mineral-enriched cultivation significantly increased the total phenolic and flavonoid contents in both crops, which was accompanied by enhanced DPPH and ABTS radical scavenging activities. Moreover, the mineral-supplemented extracts of Korean green chili pepper activated the Nrf2 signaling pathway and upregulated downstream antioxidant enzymes, including heme oxygenase-1 (HO-1), γ-glutamylcysteine ligase (GCL), and glutathione peroxidase (GPx). Notably, the mineral-supplemented Korean green chili pepper extract significantly suppressed the proliferation of human colorectal cancer cells. These findings suggest that mineral supplementation during cultivation may improve the functional quality of apples and Korean green chili peppers, supporting their potential application in cancer prevention and complementary therapeutic strategies. Full article
(This article belongs to the Special Issue Bioactive Phenolic Compounds from Agri-Food and Its Wastes)
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26 pages, 4256 KiB  
Review
Progress in Pharmacokinetics, Pharmacological Effects, and Molecular Mechanisms of Swertiamarin: A Comprehensive Review
by Hao-Xin Yang, Ying-Yue Hu, Rui Liang, Hong Zheng and Xuan Zhang
Cells 2025, 14(15), 1173; https://doi.org/10.3390/cells14151173 - 30 Jul 2025
Viewed by 155
Abstract
Swertiamarin (SW), a natural iridoid glycoside primarily isolated from the genus Swertia, Gentianaceae family, has been extensively utilized in traditional medicine systems, including Ayurveda, Traditional Chinese Medicine, and Tibetan medicine, for treating fever, diabetes, liver disorders, and inflammatory conditions. Pharmacokinetic studies reveal [...] Read more.
Swertiamarin (SW), a natural iridoid glycoside primarily isolated from the genus Swertia, Gentianaceae family, has been extensively utilized in traditional medicine systems, including Ayurveda, Traditional Chinese Medicine, and Tibetan medicine, for treating fever, diabetes, liver disorders, and inflammatory conditions. Pharmacokinetic studies reveal that SW exhibits rapid absorption but demonstrates low oral bioavailability due to the first-pass effect. Pharmacological studies have demonstrated that SW possesses a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-tumor, anti-diabetic, and neuroprotective activities. Our analysis demonstrates that SW exerts remarkable therapeutic potential across multiple pathological conditions through coordinated modulation of key signaling cascades, including Nrf2/HO-1, NF-κB, MAPK, PI3K/Akt, and PPAR pathways. This comprehensive review systematically consolidates current knowledge on SW’s pharmacokinetic characteristics, toxicity, diverse biological activities, and underlying molecular mechanisms based on extensive preclinical evidence, establishing a scientific foundation for future drug development strategies and potential clinical applications of the potential natural lead compound. Full article
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30 pages, 3414 KiB  
Article
In Vitro Neuroprotective Effects of a Mixed Extract of Bilberry, Centella asiatica, Hericium erinaceus, and Palmitoylethanolamide
by Rebecca Galla, Sara Ferrari, Ivana Miletto, Simone Mulè and Francesca Uberti
Foods 2025, 14(15), 2678; https://doi.org/10.3390/foods14152678 - 30 Jul 2025
Viewed by 49
Abstract
Oxidative stress, driven by impaired antioxidant defence systems, is a major contributor to cognitive decline and neurodegenerative processes in brain ageing. This study investigates the neuroprotective effects of a natural compound mixture—composed of Hericium erinaceus, Palmitoylethanolamide, Bilberry extract, and Centella asiatica—using [...] Read more.
Oxidative stress, driven by impaired antioxidant defence systems, is a major contributor to cognitive decline and neurodegenerative processes in brain ageing. This study investigates the neuroprotective effects of a natural compound mixture—composed of Hericium erinaceus, Palmitoylethanolamide, Bilberry extract, and Centella asiatica—using a multi-step in vitro strategy. An initial evaluation in a 3D intestinal epithelial model demonstrated that the formulation preserves barrier integrity and may be bioaccessible, as evidenced by transepithelial electrical resistance (TEER) and the expression of tight junctions. Subsequent analysis in an integrated gut–brain axis model under oxidative stress conditions revealed that the formulation significantly reduces inflammatory markers (NF-κB, TNF-α, IL-1β, and IL-6; about 1.5-fold vs. H2O2), reactive oxygen species (about 2-fold vs. H2O2), and nitric oxide levels (about 1.2-fold vs. H2O2). Additionally, it enhances mitochondrial activity while also improving antioxidant responses. In a co-culture of neuronal and astrocytic cells, the combination upregulates neurotrophic factors such as BDNF and NGF (about 2.3-fold and 1.9-fold vs. H2O2). Crucially, the formulation also modulates key biomarkers associated with cognitive decline, reducing APP and phosphorylated tau levels (about 98% and 1.6-fold vs. H2O2) while increasing Sirtuin 1 and Nrf2 expression (about 3.6-fold and 3-fold vs. H2O2). These findings suggest that this nutraceutical combination may support the cellular pathways involved in neuronal resilience and healthy brain ageing, offering potential as a functional food ingredient or dietary supplement. Full article
(This article belongs to the Section Food Nutrition)
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21 pages, 2807 KiB  
Article
Phage Therapy Enhances Survival, Immune Response, and Metabolic Resilience in Pacific White Shrimp (Litopenaeus vannamei) Challenged with Vibrio parahaemolyticus
by Chao Zeng, Long Qi, Chao-Li Guan, Yu-Lin Chang, Yu-Yun He, Hong-Zheng Zhao, Chang Wang, Yi-Ran Zhao, Yi-Chen Dong and Guo-Fang Zhong
Fishes 2025, 10(8), 366; https://doi.org/10.3390/fishes10080366 - 30 Jul 2025
Viewed by 169
Abstract
Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at [...] Read more.
Acute hepatopancreatic necrosis disease (AHPND), caused by the bacterium Vibrio parahaemolyticus, is a major threat to global shrimp aquaculture. In this study, we evaluated the therapeutic effects of phage therapy in Litopenaeus vannamei challenged with AHPND-causing Vibrio parahaemolyticus. Phage application at various concentrations significantly improved shrimp survival, with the 1 ppm group demonstrating the highest survival rate. Enzymatic assays revealed that phage-treated shrimp exhibited enhanced immune enzyme activities, including acid phosphatase (ACP), alkaline phosphatase (AKP), and lysozyme (LZM). In addition, antioxidant defenses such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and total antioxidant capacity (T-AOC) significantly improved, accompanied by reduced malondialdehyde (MDA) levels. Serum biochemical analyses demonstrated marked improvements in lipid metabolism, particularly reductions in triglyceride (TG), total cholesterol (TC), and low-density lipoprotein (LDL), alongside higher levels of beneficial high-density lipoprotein (HDL). Transcriptomic analysis identified 2274 differentially expressed genes (DEGs), notably enriched in pathways involving fatty acid metabolism, peroxisome functions, lysosomes, and Toll-like receptor (TLR) signaling. Specifically, phage treatment upregulated immune and metabolic regulatory genes, including Toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MYD88), interleukin-1β (IL-1β), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor (PPAR), indicating activation of innate immunity and antioxidant defense pathways. These findings suggest that phage therapy induces protective immunometabolic adaptations beyond its direct antibacterial effects, thereby providing an ecologically sustainable alternative to antibiotics for managing bacterial diseases in shrimp aquaculture. Full article
(This article belongs to the Special Issue Healthy Aquaculture and Disease Control)
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21 pages, 848 KiB  
Review
Food-Derived Phytochemicals: Multicultural Approaches to Oxidative Stress and Immune Response
by Eiger Gliozheni, Yusuf Salem, Eric Cho, Samuel Wahlstrom, Dane Olbrich, Brandon Shams, Michael Alexander and Hirohito Ichii
Int. J. Mol. Sci. 2025, 26(15), 7316; https://doi.org/10.3390/ijms26157316 - 29 Jul 2025
Viewed by 132
Abstract
This review will focus on how ethnic consumption of foods such as shiitake, ginseng, turmeric, black seeds, berries, rosemary, moringa and holy basil can help act as antioxidants and immune modulators in fighting many diseases. We will investigate how these foods act on [...] Read more.
This review will focus on how ethnic consumption of foods such as shiitake, ginseng, turmeric, black seeds, berries, rosemary, moringa and holy basil can help act as antioxidants and immune modulators in fighting many diseases. We will investigate how these foods act on pathways like Nrf2/Keap1 to increase endogenous antioxidant capacity and help in reducing ROS production, based on publications found in PubMed between 1994 and 2024. In addition, we will show how these plants can cause immune system shifts by changing the makeup of the ratio of Th1/Th2 cells, reduce inflammation, and have antiangiogenic effects on cancer. This review will also show how plants can alter the gut microbiota and lead to a further decrease in oxidative stress. Overall, it will show how plants and their metabolites can potentially create a path forward for creating novel therapeutic approaches and help lead to an improved redox balance, support immune function, and enhance long-term health outcomes. Full article
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16 pages, 2374 KiB  
Article
Soy Isoflavone Supplementation in Sow Diet Enhances Antioxidant Status and Promotes Intestinal Health of Newborn Piglets
by Le Liu, Lizhu Niu, Mengmeng Xu, Qing Yu, Lixin Chen, Hongyu Deng, Wen Chen and Long Che
Animals 2025, 15(15), 2223; https://doi.org/10.3390/ani15152223 - 28 Jul 2025
Viewed by 223
Abstract
This study aimed to explore the effects of dietary supplementation with soy isoflavones (SI) in the later stages of pregnancy on the antioxidant capacity of sows and intestinal health of newborn piglets. Forty sows with similar body weights and parity (average of 1–2 [...] Read more.
This study aimed to explore the effects of dietary supplementation with soy isoflavones (SI) in the later stages of pregnancy on the antioxidant capacity of sows and intestinal health of newborn piglets. Forty sows with similar body weights and parity (average of 1–2 parity) were randomly divided into two groups (n = 20): the control group and SI group (dose: 100 mg/kg of feed). Feeding was started on day 85 of gestation and continued until farrowing. SI supplementation significantly increased the antioxidant levels in the serum of the sows and newborn piglets, placental tissue, and the intestinal tract of the piglets. This observation was indicated by a decreased activity of the oxidative stress marker malondialdehyde (MDA); increased activity of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase; and enhanced total antioxidant capacity. The organ indices of the intestine and liver and the villus height/crypt depth of the jejunum of newborn piglets significantly increased. SI supplementation activated the Nrf2 signaling pathway in the jejunum of neonatal piglets and the expression of placental antioxidant proteins, and it downregulated the expression of the Bax and Caspase 3 apoptotic proteins in the placenta and neonatal piglets. Intestinal and placental barrier integrity was strengthened. For example, ZO-1, Occludin, and Claudin 1 exhibited elevated expression. In conclusion, dietary supplementation with SI enhanced the antioxidant capacity of sows and piglets and improved the health of the placenta and intestinal tract of newborn piglets. Full article
(This article belongs to the Section Pigs)
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24 pages, 1564 KiB  
Review
Anthocyanin-Rich Purple Plant Foods: Bioavailability, Antioxidant Mechanisms, and Functional Roles in Redox Regulation and Exercise Recovery
by Jarosław Nuszkiewicz, Joanna Wróblewska, Marcin Wróblewski and Alina Woźniak
Nutrients 2025, 17(15), 2453; https://doi.org/10.3390/nu17152453 - 28 Jul 2025
Viewed by 385
Abstract
Anthocyanin-rich purple fruits and vegetables—such as blackcurrants, blueberries, purple sweet potatoes, and red cabbage—are increasingly recognized for their health-promoting properties. These natural pigments exert antioxidant and anti-inflammatory effects, making them relevant to both chronic disease prevention and exercise recovery. This review critically examines [...] Read more.
Anthocyanin-rich purple fruits and vegetables—such as blackcurrants, blueberries, purple sweet potatoes, and red cabbage—are increasingly recognized for their health-promoting properties. These natural pigments exert antioxidant and anti-inflammatory effects, making them relevant to both chronic disease prevention and exercise recovery. This review critically examines current evidence on the redox-modulating mechanisms of anthocyanins, including their interactions with key signaling pathways such as Nrf2 and NF-κB, and their effects on oxidative stress, mitochondrial function, vascular homeostasis, and post-exercise adaptation. Particular attention is given to their bioavailability and the challenges associated with their chemical stability, metabolism, and food matrix interactions. In light of these factors, dietary strategies and technological innovations to improve anthocyanin absorption are also discussed. The synthesis of preclinical and clinical findings supports the potential of anthocyanin-rich foods as functional components in health optimization, athletic performance, and recovery strategies. Full article
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23 pages, 2594 KiB  
Article
A Natural Polyphenol, Chlorogenic Acid, Attenuates Obesity-Related Metabolic Disorders in Male Rats via miR-146a-IRAK1-TRAF6 and NRF2-Mediated Antioxidant Pathways
by Rashid Fahed Alenezi, Adel Abdelkhalek, Gehad El-Sayed, Ioan Pet, Mirela Ahmadi, El Said El Sherbini, Daniela Pușcașiu and Ahmed Hamed Arisha
Biomolecules 2025, 15(8), 1086; https://doi.org/10.3390/biom15081086 - 27 Jul 2025
Viewed by 193
Abstract
Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, [...] Read more.
Chronic high-fat diet (HFD) feeding in male rats causes significant metabolic as well as inflammatory disturbances, including obesity, insulin resistance, dyslipidemia, liver and kidney dysfunction, oxidative stress, and hypothalamic dysregulation. This study assessed the therapeutic effects of chlorogenic acid (CGA), a natural polyphenol, administered at 10 mg and 100 mg/kg/day for the last 4 weeks of a 12-week HFD protocol. Both CGA doses reduced body weight gain, abdominal circumference, and visceral fat accumulation, with the higher dose showing greater efficacy. CGA improved metabolic parameters by lowering fasting glucose and insulin and enhancing lipid profiles. CGA suppressed orexigenic genes (Agrp, NPY) and upregulated anorexigenic genes (POMC, CARTPT), suggesting appetite regulation in the hypothalamus. In abdominal white adipose tissue (WAT), CGA boosted antioxidant defenses (SOD, CAT, GPx, HO-1), reduced lipid peroxidation (MDA), and suppressed pro-inflammatory cytokines including TNF-α, IFN-γ, and IL-1β, while increasing the anti-inflammatory cytokine IL-10. CGA modulated inflammatory signaling via upregulation of miR-146a and inhibition of IRAK1, TRAF6, and NF-κB. It also reduced apoptosis by downregulating p53, Bax, and Caspase-3, and restoring Bcl-2. These findings demonstrate that short-term CGA administration effectively reverses multiple HFD-induced impairments, highlighting its potential as an effective therapeutic for obesity-related metabolic disorders. Full article
(This article belongs to the Special Issue Antioxidant and Anti-Inflammatory Activities of Phytochemicals)
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16 pages, 3840 KiB  
Article
Parishin C Attenuates Oxidative Stress and Inflammation in HT22 Hippocampal Neurons and BV2 Microglia Through Nrf2 Signaling Pathway
by Yichen Wang, Wenze Wu, Xinyan Wu, Basit Ali Shah, Mauro Lombardo and Gang Ye
Int. J. Mol. Sci. 2025, 26(15), 7263; https://doi.org/10.3390/ijms26157263 - 27 Jul 2025
Viewed by 347
Abstract
Parishin C (PaC) is an active ingredient in Gastrodia elata Bl. that has neuroprotective effects. However, research on its role in oxidative stress and neuroinflammation is still limited. This study used LPS–stimulated HT22 cells to investigate the antioxidant properties of PaC. Through the [...] Read more.
Parishin C (PaC) is an active ingredient in Gastrodia elata Bl. that has neuroprotective effects. However, research on its role in oxidative stress and neuroinflammation is still limited. This study used LPS–stimulated HT22 cells to investigate the antioxidant properties of PaC. Through the co–culture system of HT22 and BV2 cells, the effect of PaC on neuroinflammation was explored. The current results indicated that PaC can inhibit the levels of reactive oxygen species and peroxides in LPS–stimulated HT22 cells and increase the levels of antioxidant factors. Meanwhile, PaC can also inhibit neuronal ferroptosis and the levels of pro–inflammatory cytokines in BV2 cells. Importantly, the antioxidant and anti–inflammatory effects of PaC are achieved by activating the Nrf2 signaling pathway. The WB and IF results indicated that PaC can promote nuclear translocation of Nrf2, activate downstream antioxidant factors, and thereby regulate inflammatory responses. Inhibition of Nrf2 can significantly inhibit the regulation of PaC on the Nrf2 signaling pathway. These results indicated that PaC can activate the Nrf2 signaling pathway to inhibit oxidative stress and inflammation. Full article
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26 pages, 5270 KiB  
Article
Gallic Acid and Taurine Attenuate Thiamethoxam-Induced Hepatotoxicity in Rats by Modulating SIRT-1/PGC-1α, NF-κB/iNOS, and p53/Bax/Caspase-3 Pathways
by Sara T. Elazab, Fatmah A. Safhi, Rasha K. Al-Akeel, Raghda H. Deraz, Souvarish Sarkar and Rania Essam Ali Gamal Eldin
Pharmaceuticals 2025, 18(8), 1112; https://doi.org/10.3390/ph18081112 - 25 Jul 2025
Viewed by 353
Abstract
Background/Objectives: Thiamethoxam (TMX) is one of the most extensively utilized insecticides of the neonicotinoid family; however, its application is associated with notable toxic effects on multiple organs of mammals. Our purpose was to explore the potential hepatoprotective effect of taurine (TAU) and/or [...] Read more.
Background/Objectives: Thiamethoxam (TMX) is one of the most extensively utilized insecticides of the neonicotinoid family; however, its application is associated with notable toxic effects on multiple organs of mammals. Our purpose was to explore the potential hepatoprotective effect of taurine (TAU) and/or gallic acid (GA) against TMX-induced liver damage, with an emphasis on their role in regulating SIRT-1/PGC-1α, NF-κB/iNOS, and p53/Bax/caspase-3 pathways. Methods: Rats were assigned to seven groups (n = 6) and gavaged daily for 28 days with saline (control group), TAU at 50 mg/kg, GA at 20 mg/kg, TMX at 78.15 mg/kg, TMX + TAU, TMX + GA, and TMX + TAU + GA. Results: The findings revealed that TAU and/or GA attenuated TMX-induced liver injury, as demonstrated by the restoration of hepatic performance hallmarks and histological structure. TAU and GA mitigated TMX-mediated oxidative stress and boosted the antioxidant defense mechanism by upregulating the transcription levels of SIRT-1, PGC-1α, Nrf2, and HO-1. Moreover, TAU and GA suppressed TMX-associated inflammatory response by increasing IL-10 concentration and lowering the levels of NF-κB, IL-1β, and iNOS; the mRNA levels of NLRP3; and TNF-α immunoexpression. Both compounds, individually or concurrently, exerted an anti-apoptotic effect in TMX-treated rats, evidenced by increased Bcl-2 expression and reduced p53 mRNA level, Bax expression, and caspase-3 concentration. Conclusions: TAU and/or GA may be regarded as promising remedies that can alleviate TMX-induced hepatotoxicity by activating SIRT-1/PGC-1α signaling and abolishing inflammation and apoptosis. Full article
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18 pages, 2943 KiB  
Article
Cadmium Inhibits Proliferation of Human Bronchial Epithelial BEAS-2B Cells Through Inducing Ferroptosis via Targeted Regulation of the Nrf2/SLC7A11/GPX4 Pathway
by Huan Li, Zixin Qiu, Long Chen, Tianbao Zhang, Diandian Wei, Xue Chen and Yun Wang
Int. J. Mol. Sci. 2025, 26(15), 7204; https://doi.org/10.3390/ijms26157204 - 25 Jul 2025
Viewed by 178
Abstract
Cadmium (Cd)-induced pulmonary toxicity is closely associated with ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation (LPO). Luteolin (Lut) is a natural flavonoid compound that exists in many plants. In this study, we used human bronchial epithelial BEAS-2B cells [...] Read more.
Cadmium (Cd)-induced pulmonary toxicity is closely associated with ferroptosis, a regulated form of cell death characterized by iron-dependent lipid peroxidation (LPO). Luteolin (Lut) is a natural flavonoid compound that exists in many plants. In this study, we used human bronchial epithelial BEAS-2B cells to explore the impact of ferroptosis in the inhibition of Cd-induced BEAS-2B cells proliferation. BEAS-2B cells were exposed to Cd (5 μM) with/without Lut (10 μM), ferroptosis modulators (Ferrostatin-1 (Fer-1)/Erastin), or nuclear factor erythroid 2-related factor 2 (Nrf2) regulators (tert-butylhydroquinone (TBHQ)/ML385). Viability, iron content, reactive oxygen species (ROS), LPO, mitochondrial membrane potential (MMP), and glutathione peroxidase (GSH-PX) activity were assessed. Exposure to Cd significantly decreased cell viability, increased intracellular iron levels, ROS production, and LPO activity, while simultaneously reducing MMP and GSH-PX activity. Fer-1 mitigated Cd-induced cytotoxicity, but Erastin intensified these effects. Mechanistically, Cd exposure suppressed the Nrf2/Solute Carrier Family 7 Member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway, which plays a crucial role in maintaining redox homeostasis. Activation of Nrf2 using TBHQ mitigated oxidative stress and upregulated the expression of key proteins within this pathway, while inhibition of Nrf2 with ML385 exacerbated cellular damage. Notably, Lut treatment could significantly alleviate Cd-induced cytotoxicity, oxidative stress, and downregulation of Nrf2/SLC7A11/GPX4 proteins. These findings demonstrate that ferroptosis is a critical mechanism underlying Cd-mediated lung epithelial injury and identify Lut as a promising therapeutic candidate via its activation of Nrf2-driven antioxidant defense mechanisms. This study provides novel insights into molecular targets for the prevention and treatment of Cd-associated pulmonary disorders. Full article
(This article belongs to the Section Biochemistry)
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18 pages, 2205 KiB  
Article
Lupeol Attenuates Oxysterol-Induced Dendritic Cell Activation Through NRF2-Mediated Antioxidant and Anti-Inflammatory Effects
by Sarmistha Saha, Antonella Capozzi, Elisabetta Profumo, Cristiano Alessandri, Maurizio Sorice, Luciano Saso and Brigitta Buttari
Int. J. Mol. Sci. 2025, 26(15), 7179; https://doi.org/10.3390/ijms26157179 - 25 Jul 2025
Viewed by 153
Abstract
Oxysterols such as 7-ketocholesterol (7KCh) contribute to the pathogenesis of autoimmune and chronic inflammatory diseases by inducing oxidative stress and promoting pro-inflammatory immune cell activation. Dendritic cells (DCs) play a central role in maintaining immune tolerance, and their dysregulation is a key driver [...] Read more.
Oxysterols such as 7-ketocholesterol (7KCh) contribute to the pathogenesis of autoimmune and chronic inflammatory diseases by inducing oxidative stress and promoting pro-inflammatory immune cell activation. Dendritic cells (DCs) play a central role in maintaining immune tolerance, and their dysregulation is a key driver of autoimmunity. Targeting DCs by using natural compounds offers a promising strategy to restore redox balance and suppress aberrant immune responses. This study investigated the immunomodulatory and antioxidant properties of Lupeol, a natural triterpenoid, in human monocyte-derived DCs exposed to 7KCh. Flow cytometry and cytokine profiling demonstrated that Lupeol preserved the immature, tolerogenic phenotype of DCs by promoting a dose-dependent increase in the anti-inflammatory cytokine IL-10. Lupeol also inhibited the 7KCh-induced upregulation of maturation markers (CD83, CD86) and suppressed the release of pro-inflammatory cytokines IL-1β and IL-12p70. Functionally, Lupeol-treated DCs directed T cell polarization toward an anti-inflammatory and regulatory profile while dampening the inflammatory responses triggered by 7KCh. This immunoregulatory effect was further supported by the decreased secretion of the pro-inflammatory cytokines IL-1β and IL-12p70 in DC culture supernatants. Mechanistic analyses using immunofluorescence showed that Lupeol alone significantly increased nuclear NRF2 levels and upregulated HO-1 expression. Western blot analysis further confirmed Lupeol’s ability to activate the KEAP1-NRF2 signaling pathway, as evidenced by increased expression of NRF2 and its downstream target, NQO1. The use of ML385, a selective NRF2 inhibitor, in ROS and cytokine assays supported the involvement of NRF2 in mediating the Lupeol antioxidant and anti-inflammatory effects in DCs. Notably, the oxidative burden induced by 7KCh limited the full activation of NRF2 signaling triggered by Lupeol. Furthermore, docking and MM/PBSA analyses revealed the specific interactions of Lupeol with the kelch domain of KEAP1. These findings suggest that Lupeol may serve as a promising orally available immunomodulatory agent capable of promoting tolerogenic DCs, offering potential applications in autoimmune and other chronic inflammatory diseases. Full article
(This article belongs to the Special Issue Updates on Synthetic and Natural Antioxidants)
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