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MOLECULAR AND CELLULAR ENDOCRINOLOGY · 2022 · IF 4.369

Inhibition of Nicotinamide adenine dinucleotide phosphate oxidase 4 attenuates cell apoptosis and oxidative stress in a rat model of polycystic ovary syndrome through the activation of Nrf-2/HO-1 signaling pathway

Yan Li,Jia Xu,Lingxia Li,Lu Bai,Yunping Wang,Jianfang Zhang,Haixu Wang

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in reproductive-aged women. In this study, a rat model of PCOS was established by subcutaneous injection of dehydroepiandrosterone (DHEA). NOX4 was highly expressed in PCOS rat ovaries, while its specific role in PCOS remains unclear. Lentivirus-mediated shRNA targeting NOX4 inhibited oxidative stress by reducing ROS, 4-HNE and MDA levels, and increasing SOD and GPX activities in rat ovaries. NOX4 deficiency increased Bcl-2 levels and decreased Bax, cleaved caspase-3 and cleaved caspase-9 levels and DHEA-induced cell apoptosis in rat ovaries. Similar to the in vivo results, NOX4 silencing inhibited oxidative stress and cell apoptosis in DHEA-treated rat granulosa cells . Moreover, NOX4 silencing promoted Nrf-2 translocation, and the expression of Nrf-2 and HO-1 both in vivo and in vitro . Thus, NOX4 deficiency may ameliorate PCOS in rats by reducing oxidative stress and cell apoptosis via activating the Nrf-2/HO-1 signal pathway .

CAS / MDL: 53-43-0
研究领域: 生殖内分泌学 · 分子生物学 · 细胞生物学 · 氧化应激 · 细胞凋亡
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AMB Express · 2024 ·Vol. 14 ·期 1 ·1-16 · IF 3.5

Seabuckthorn polysaccharides mitigate hepatic steatosis by modulating the Nrf-2/HO-1 pathway and gut microbiota

Yan Yan,Yuan Haisheng,Yang Fan,Na Heiya,Yu Xiuling,Liu Jingran,Wang Yuzhen

Non-alcoholic fatty liver disease (NAFLD) is becoming a significant global public health threat. Seabuckthorn ( Hippophae rhamnoides L.) has been used in traditional Chinese medicine (TCM). The hypolipidemic effects of Seabuckthorn polysaccharides (SP) against high-fat diets (HFD)-induced NAFLD were systematically explored and compared with that of Bifidobacterium lactis V9 ( B. Lactis V9). Results showed that HFD-induced alanine transaminase (ALT) and aspartate aminotransferase (AST) levels decreased by 2.8-fold and 4.5-fold, respectively, after SP supplementation. Moreover, the alleviating effect on hepatic lipid accumulation is better than that of B. Lactis V9. The ACC and FASN mRNA levels were significantly reduced by 1.8 fold ( P  < 0.05) and 2.3 folds ( P  < 0.05), respectively, while the CPT1α and PPARα mRNA levels was significantly increased by 2.3 fold ( P  < 0.05) and 1.6 fold ( P  < 0.05), respectively, after SP administration. SP activated phosphorylated-AMPK and inhibited PPARγ protein expression, improved serum oxidative stress and inflammation ( P  < 0.05). SP supplementation leads to increased hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) and Superoxide dismutase-2 (SOD-2). Furthermore, SP treatment improved HFD-induced intestinal dysbiosis. Lentisphaerae , Firmicutes , Tenericutes and Peptococcus sp., RC9_gut_group sp., and Parabacteroides sp. of the gut microbiota were significantly associated with hepatic steatosis and indicators related to oxidative stress and inflammation. Therefore, SP can mitigate hepatic lipid accumulation by regulating Nrf-2/HO-1 signaling pathways and gut microbiota. This study offers new evidence supporting the use of SP as a prebiotic treatment for NAFLD.

CAS / MDL: 633-65-8
研究领域: 药理学 · 肝病学 · 营养学 · 微生物学 · 分子生物学
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Frontiers in Pharmacology · 2024 · IF 4.4

Hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles inhibit neuronal death after spinal cord injury by regulating the SIRT1/Nrf2/HO-1 pathway

Rao Jian,Xie Haishu,Liang Zeyan,Yang Zhelun,Chen Pingping,Zhou Maochao,Xu Xiongjie,Lin Yike,Lin Fabin,Wang Rui,Wang Chunhua,Chen Chunmei

Background: Oxidative stress and apoptosis of neurons significantly contribute to the pathophysiological cascade of spinal cord injury (SCI). However, the role of hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles (H-sEVs) in promoting SCI repair remains unclear. Hence, the present study aims to investigate the regulatory effects of H-sEVs on neuronal oxidative stress and apoptotic responses following SCI.Methods: The administration of H-sEVs of SCI rats was assessed using behavioral evaluations such as Basso-Beattie-Bresnahan (BBB) scores, neuroelectrophysiological monitoring, and Catwalk gait analysis. Indices of oxidative stress (including superoxide dismutase [SOD], total antioxidant capacity [T-AOC], and malondialdehyde [MDA]) were measured. Neuronal survival was evaluated through Nissl staining, while the expression level of sirtuin 1 (SIRT1) was examined using immunohistochemical staining. Additionally, histological evaluation of lesion size was performed using hematoxylin-eosin (HE) staining. Tunel cell apoptosis staining and analysis of apoptosis-associated proteins (B-cell lymphoma-2 [Bcl2] and BCL2-Associated X [Bax]) were conducted through immunofluorescence staining and western blot, respectively. Furthermore, the model of oxidative stress was established using PC12 cells, and apoptosis levels were assessed via flow cytometry and western blot analysis. Importantly, to ascertain the critical role of SIRT1, we performed SIRT1 knockout experiments in PC12 cells using lentivirus transfection, followed by western blot.Results: Using those behavioral evaluations, we observed significant functional improvement after H-sEVs treatment. Nissl staining revealed that H-sEVs treatment promoted neuronal survival. Moreover, we found that H-sEVs effectively reduced oxidative stress levels after SCI. HE staining demonstrated that H-sEVs could reduce lesion area. Immunohistochemical analysis revealed that H-sEVs enhanced SIRT1 expression. Furthermore, Tunel cell apoptosis staining and western blot analysis of apoptosis-related proteins confirmed the anti-apoptotic effects of H-sEVs. The PC12 cells were used to further substantiate the neuroprotective properties of H-sEVs by significantly inhibiting neuronal death and attenuating oxidative stress. Remarkably, SIRT1 knockout in PC12 cells reversed the antioxidant stress effects induced by H-sEVs treatment. Additionally, we elucidated the involvement of the downstream Nrf2/HO-1 signaling pathway.Conclusion: Our study provides valuable insights into the effects of H-sEVs on neuronal oxidative stress and apoptosis after SCI. These findings underscore the potential clinical significance of H-sEVs-based therapies for SCI.

CAS / MDL: 7722-84-1
研究领域: 神经科学 · 干细胞生物学 · 分子生物学 · 细胞生物学 · 再生医学
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Oxidative Medicine and Cellular Longevity · 2021 · IF 6.543

HO-1/CO Maintains Intestinal Barrier Integrity through NF-κB/MLCK Pathway in Intestinal HO-1-/- Mice

Zhenling Zhang,Lijing Zhang,Qiuping Zhang,Bojia Liu,Fang Li,Yi Xin,Zhijun Duan

Background. Intestinal barrier injury is an important contributor to many diseases. We previously found that heme oxygenase-1 (HO-1) and carbon monoxide (CO) protect the intestinal barrier. This study is aimed at elucidating the molecular mechanisms of HO-1/CO in barrier loss. Materials and Methods. We induced gut leakiness by injecting carbon tetrachloride (CCl4) to wildtype or intestinal HO-1-deficient mice. In addition, we administrated tumor necrosis factor-α (TNF-α) to cells with gain- or loss-of-HO-1 function. The effects of HO-1/CO maintaining intestinal barrier integrity were investigated in vivo and in vitro. Results. Cobalt protoporphyrin and CO-releasing molecule-2 alleviated colonic mucosal injury and TNF-α levels; upregulated tight junction (TJ) expression; and inhibited epithelial IκB-α degradation and phosphorylation, NF-κB p65 phosphorylation, long MLCK expression, and MLC-2 phosphorylation after administration of CCl4. Zinc protoporphyrin completely reversed these effects. These findings were further confirmed in vitro, using Caco-2 cells with gain- or loss-of-HO-1-function after TNF-α. Pretreated with JSH-23 (NF-κB inhibitor) or ML-7 (long MLCK inhibitor), HO-1 overexpression prevented TNF-α-induced TJ disruption, while HO-1 shRNA promoted TJ damage even in the presence of JSH-23 or ML-7, thus suggesting that HO-1 dependently protected intestinal barrier via the NF-κB p65/MLCK/p-MLC-2 pathway. Intestinal HO-1-deficient mice further demonstrated the effects of HO-1 in maintaining intestinal barrier integrity and its relative mechanisms. Alleviated hepatic fibrogenesis and serum ALT levels finally confirmed the clinical significance of HO-1/CO repairing barrier loss in liver injury. Conclusion. HO-1/CO maintains intestinal barrier integrity through the NF-κB/MLCK pathway. Therefore, the intestinal HO-1/CO-NF-κB/MLCK system is a potential therapeutic target for diseases with a leaky gut.

CAS / MDL: 56-23-5
研究领域: 胃肠病学 · 免疫学 · 药理学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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NEUROCHEMICAL RESEARCH · 2022 ·Vol. 48 ·期 5 ·1305-1319 · IF 4.414

Gelsemine Exerts Neuroprotective Effects on Neonatal Mice with Hypoxic-Ischemic Brain Injury by Suppressing Inflammation and Oxidative Stress via Nrf2/HO-1 Pathway

Cheng Shen,Chen Chen,Wang Liling

Given that the role of Gelsemine in neuroinflammation has been demonstrated, this research aimed to investigate the effect of Gelsemine on neonatal hypoxic-ischemic (HI) brain injury. An in vivo HI brain injury neonatal mouse model and an in vitro oxygen–glucose deprivation (OGD) cell model were established and pretreated with Gelsemine. The brain infarct volume, neuronal loss and apoptosis, as well as spatial learning and memory were examined by TTC staining, Nissl’s staining, TUNEL staining and Morris water maze test. Immunohistochemical staining was applied to detect the microglia cells and astrocytes in the mouse brain tissue. The cell viability was analyzed by CCK-8 assay. The levels of malondialdehyde (MDA), superoxide dismutase (SOD), TNF-α, IL-1β, and IL-6 were determined via ELISA. The lactate dehydrogenase (LDH) release and reactive oxygen species (ROS) level in OGD-treated cells were detected by colorimetry and DCFH-DA staining. Nrf2, HO-1, and inflammation-related factors were analyzed by immunofluorescence, qRT-PCR, or western blot. Gelsemine reduced the infarct volume and neuronal loss and apoptosis, yet improved spatial learning and memory impairment of HI-injured mice. Gelsemine inhibited the elevated MDA, TNF-α, IL-1β, IL-6, LDH and ROS levels, promoted the reduced SOD level and viability, and strengthened the up-regulation of HO-1 and Nrf2 in brain tissues and OGD-treated cells. However, Nrf2 silencing reversed the effects of Gelsemine on the Nrf2/HO-1 pathway, inflammation, and oxidative stress in OGD-treated cells. Gelsemine produces neuroprotective effects on neonatal mice with HI brain injury by suppressing inflammation and oxidative stress via Nrf2/HO-1 pathway.

CAS / MDL: 64-17-5
研究领域: 神经科学 · 药理学 · 分子生物学 · 细胞生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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EXPERIMENTAL CELL RESEARCH · 2023 · IF 3.7

Punicalagin attenuates TNF-α-induced oxidative damage and promotes osteogenic differentiation of bone mesenchymal stem cells by activating the Nrf2/HO-1 pathway

Lei Huang,Shunyi Lu,Mengxuan Bian,Jiayi Wang,Jieqin Yu,Jun Ge,Jian Zhang,Qintong Xu

Oxidative stress is one of the most important factors in changing bone homeostasis. Redox homeostasis plays a key role in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) for bone regeneration. Currently, this study assessed the effects of punicalagin (PUN) on BMSCs and HUVECs. Cell viability was determined by CCK-8 assay. A flow cytometry analysis was adopted to detect macrophage polarization. The production of reactive oxygen stress (ROS), glutathione (GSH), malonaldehyde (MDA) and superoxide dismutase (SOD) activities were evaluated by using commercially-available kits. Osteogenic capacity of BMSCs was evaluated by ALP activity, ALP staining and ARS staining. The expression of osteogenic-related proteins (OCN, Runx-2, OPN) and Nrf/HO-1 levles were evaluated by Western blotting. Osteogenic-related genes (Osterix, COL-1, BMP-4, ALP) were evaluated by RT-PCR. Migration ability and invasion ability of HUVECs were evaluated by wound healing assay and Transwell assay. Angiogenic ability was detected by tube formation assay and the expression of angiogenic-related genes (VEGF, vWF, CD31) were evaluated by RT-PCR. Results showed that PUN alleviated oxidative stress by TNF-α, enhanced osteogenic differentiation in BMSCs and angiogenesis in HUVECs. Moreover, PUN regulate immune microenvironment by promoting the polarization of M2 macrophages and reduce the oxidative stress related products by activating Nrf2/HO-1 pathway. Altogether, these results suggested that PUN can promote osteogenic capacity of BMSCs, angiogenesis of HUVECs, alleviate oxidative stress via Nrf2/HO-1 pathway, offering PUN as a novel antioxidant agent for treating bone loss diseases.

CAS / MDL: 30525-89-4
研究领域: 药理学 · 细胞生物学 · 分子生物学 · 干细胞研究 · 骨再生
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RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY · 2025 ·Vol. 51 ·期 5 ·2152-2169 · IF 1.7

Synthesis of Formononetin Derivatives and Their Protective Effects Against Oxidative Stress

Luo Zeping,Pan Liwei

Objective: With the molecular formula C 16 H 12 O 4 , formononetin (FMN) is an appealing synthon exhibiting a wide range of biological activities, including antioxidant, anti-infective, and anti-apoptotic effects. Due to increasing interest in the mechanisms of action of antioxidants, our group aimed to identify the cellular target sites of these compounds. Methods: Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM), TdT-mediated dUTP nick end labeling (TUNEL) staining, real-time quantitative polymerase chain reaction (RT-qPCR), and Western blot were used to analyze the effects of oxidative stress on PC12 cell survival, antioxidant enzyme activity, mitochondrial morphology, apoptosis, key intracellular proteins, and signaling pathways. The potential roles of candidate targets were further investigated using proteomics, molecular docking, kinetic simulation, and cellular thermal shift assay (CETSA). Results and Discussion: One of the compounds, ( VI ) (5-(8-(((1-(benzyloxy)-3-hydroxy-1-oxopropan-2-yl)amino)methyl)-7-hydroxy-4-oxo-4 H -chromen-3-yl)-2-methoxybenzenesulfonic acid), was highly active. It enhanced PC12 cell proliferation, reduced lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, and increased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities, effectively inhibiting apoptosis and ameliorating mitochondrial damage. Meanwhile, ( VI ) upregulated the expression of PI3K/Akt and Nrf2/HO-1 proteins. The study also demonstrated that ( VI ) binds significantly to the oxidative stress-related protein HO-1. Conclusions: Compound ( VI ) effectively protects PC12 cells against H 2 O 2 -induced oxidative damage. Its protective mechanism may involve activation of the PI3K/Akt and Nrf2/HO-1 signaling pathways, with HO-1 serving as a potential key target of its action.

CAS / MDL: 9087-70-1
研究领域: 药理学 · 分子生物学 · 神经科学 · 药物化学 · 细胞生物学 · 抗氧化研究 · 信号转导
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CHEMICAL ENGINEERING JOURNAL · 2015 · IF 4.321

Mechanism of PCE oxidation by percarbonate in a chelated Fe(II)-based catalyzed system

Zhouwei Miao,Xiaogang Gu,Shuguang Lu,Dionysios D. Dionysiou,Souhail R. Al-Abed,Xueke Zang,Xiaoliang Wu,Zhaofu Qiu,Qian Sui,Muhammad Danish

The performance of chelated Fe(II)-based catalyzed sodium percarbonate (SPC) stimulating the degradation of perchloroethylene (PCE) in aqueous solution was investigated using six different chelating agents (CA), namely, citric acid monohydrate (CIT), oxalic acid (OA), l -ascorbic acid (ASC), ethylenediaminetetraacetic acid (EDTA), trisodium citrate 2-hydrate (CIT-Na 3 ), and EDTA-Na 2 , at CA/Fe(II)/SPC/PCE molar ratios of 2/4/4/1, 4/4/4/1 and 8/4/4/1. The results indicated that the addition of CIT and OA significantly enhanced the PCE degradation. In addition, investigations using free radical probe compounds and radical scavengers revealed that PCE was primarily degraded by HO radical oxidation in Fe(II)/SPC, CIT/Fe(II)/SPC, and OA/Fe(II)/SPC systems and O 2 − also participated in the degradation of PCE in CIT/Fe(II)/SPC and OA/Fe(II)/SPC systems. The intensity of HO detected by electron paramagnetic resonance (EPR) in CIT/Fe(II)/SPC and OA/Fe(II)/SPC systems indicated that the addition of CIT or OA indeed enhanced the continuous production of HO and enabled the intensity of HO to be more stable. The results demonstrated that CIT and OA significantly improved the PCE degradation efficiency by increasing the concentration of Fe(II) and maintaining the concentration of HO radicals in solution. In conclusion, chelated Fe(II)-based catalyzed SPC oxidation process shows enormous practical prospects for the remediation of PCE-contaminated groundwater because of the effectiveness without pre-adjusting the solution pH and complete mineralization in Fe(II)/SPC, CIT/Fe(II)/SPC and OA/Fe(II)/SPC systems.

研究领域: 环境科学 · 化学
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE · 2025 · IF 3.5

Purification, characterization and protective effects on UVB-induced photoaging in zebrafish of Pleurotus citrinopileatus polysaccharide PCP-2

Yan-Xia Li,He Ma,Le Shi,Zhong-Fei Zhang,Yu-Meng Wu,Chao Yan,Yan Chen,Yong-Ming Lu

BACKGROUND Polysaccharides from Pleurotus citrinopileatus exhibit diverse bioactivities, yet their efficacy against ultraviolet B (UVB)-induced photoaging remains unexplored. This study aimed to purify and characterize a specific PCP and assess its protective effects using a UVB-induced zebrafish model. RESULTS A polysaccharide, designated as PCP-2, was isolated from P. citrinopileatus through hot-water extraction, ultrafiltration and chromatography. PCP-2 is a galactoglucan with a molecular weight of 1.52 × 10 6 Da, predominantly composed of 1,4-linked glucopyranosyl and 1,4,6-linked galactopyranosyl residues. In UVB-exposed zebrafish, PCP-2 administration resulted in a significant reduction of reactive oxygen species and malondialdehyde levels, alongside enhanced activities of antioxidant enzymes, including superoxide dismutase, catalase and glutathione peroxidase. Additionally, PCP-2 inhibited apoptosis by upregulating Bcl-2 expression and downregulating caspase-3. It also attenuated cellular senescence, as indicated by decreased β -galactosidase activity and increased telomerase activity. Moreover, PCP-2 promoted the synthesis of type I and III collagen by suppressing matrix metalloproteinases MMP-1 and MMP-3 and reduced melanin production through the downregulation of tyrosinase expression. Mechanistic studies suggested that these protective effects are mediated via activation of the Nrf2/HO-1 signaling pathway. CONCLUSION PCP-2 from P. citrinopileatus effectively mitigates UVB-induced photoaging, primarily by activating the Nrf2/HO-1 pathway. These findings suggest PCP-2's potential as an anti-photoaging agent in both food and pharmaceutical industries. © 2025 Society of Chemical Industry.

CAS / MDL: 9002-10-2
研究领域: 生物化学 · 药理学 · 食品科学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CRYOGENICS · 2022 · IF 2.134

Magnetocaloric effect in LiLn6O5(BO3)3 (Ln = Gd, Tb, Dy, and Ho)

Yuwei Chen,Wang Liu,Jingcheng Feng,Ruixin Guo,Feidi Fan,Jun Shen,Guochun Zhang,Heng Tu

A series of lanthanide-rich oxyborates LiLn 6 O 5 (BO 3 ) 3 (LLnOB, Ln = Gd, Tb, Dy, and Ho) have been synthesized using high temperature solid state method. Their magnetic and magnetocaloric properties were investigated upon magnetic susceptibility ( χ ), magnetization ( M ), and isothermal magnetic entropy change ( −ΔS m ) measurements. The maximum  − ΔS m, max of LiGd 6 O 5 (BO 3 ) 3 is 44.7 J kg −1 K −1 at 4 K and Δμ 0 H  = 9 T, which is higher than the one of commercial Gd 3 Ga 5 O 12 (GGG, −ΔS m, max  = 41.8 J kg −1 K −1 at 2 K for Δμ 0 H  = 9 T). For LiHo 6 O 5 (BO 3 ) 3 , −ΔS m, max is 14.12 J kg −1  K −1 at 3 K and Δμ 0 H  = 2 T, which is also larger than that of Ho 3 Ga 5 O 12 (HoGG, − ΔS m, max  = 4.38 J kg −1 K −1 at 2 K for Δμ 0 H  = 2 T) and Dy 3 Ga 5 O 12 (DGG, − ΔS m, max  = 11.0 J kg −1 K −1 at 2 K for Δμ 0 H  = 2 T). These results indicate that LiGd 6 O 5 (BO 3 ) 3 and LiHo 6 O 5 (BO 3 ) 3 may be competitive candidates for applications as magnetic refrigerants. Moreover, thermal stability, infrared spectrum (IR), and ultraviolet–visible-near-infrared diffuse reflectance spectrum (UV–Vis-NIR) were carried out to characterize the title compounds.

研究领域: 材料科学 · 物理学 · 化学
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Scientific Reports · 2025 ·Vol. 15 ·期 1 ·1-12 · IF 3.9

Cordycepin combined with antioxidant effects improves fatigue caused by excessive exercise

Cheng Chunfang,Zhang Shasha,Chen Chong,Gong Yanchun,Ding Kaizhi,Li Guoyin,Jiang Wei,Zhang Zhenyu,He Bin,Hu Zhihong,Li Yuhua,Yao Lihua

Excessive exercise can lead to physical fatigue and disruption of the antioxidant system, resulting in neurological damage and cognitive decline. Cordycepin, the main component of Cordyceps militaris , has anti-inflammatory, antioxidant and neuroprotective effects. In this study, the anti-fatigue effect and potential mechanism of action of cordycepin were investigated using a forced exercise mouse model. The results showed that oral administration of cordycepin enhanced exercise endurance, increased liver and muscle glycogen content, and simultaneously decreased serum levels of lactic acid, lactate dehydrogenase, creatine kinase, and blood urea nitrogen ( p  < 0.05). In addition, cordycepin had antioxidant effects, increasing superoxide dismutase activity and decreasing serum malondialdehyde (MDA) levels ( p  < 0.01). In vitro experiments further demonstrated the antioxidant and anti-fatigue effects of cordycepin. Behavioral tests showed that the learning and memory ability of mice in the excessive exercise model group decreased to 40% compared with the control group. Cordycepin alleviated the learning and memory deficits in the over-exercised mice, significantly reduced the levels of fatigue metabolites and oxidative stress in vivo ( p  < 0.05), and altered the levels of neurotransmitters levels ( p  < 0.05). Furthermore, cordycepin modulated Keap1/Nrf2/HO-1-mediated oxidative stress and enhanced BDNF levels ( p  < 0.05). These findings suggest that cordycepin can alleviate excessive exercise-induced fatigue by modulating the Keap1/Nrf2/HO-1 signaling pathway and BDNF expression, providing strong supporting evidence for the development of cordycepin-functional foods or anti-fatigue drugs.

研究领域: 运动生理学 · 药理学 · 神经科学
✓ 已验证 DOI PubMed 高影响因子
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Antioxidants · 2023 ·Vol. 12 ·期 2 ·370 · IF 7

Nootkatone Supplementation Attenuates Carbon Tetrachloride Exposure-Induced Nephrotoxicity in Mice

Chongshan Dai,Mingchao Liu,Qinzhi Zhang,Subhajit Das Gupta,Shusheng Tang,Jianzhong Shen

Nootkatone (NKT), a major ingredient of Alpinia oxyphylla, exhibited potential nephroprotective effects; however, the precise molecular mechanisms remain poorly understood. This study aimed to study the nephroprotective effects of NKT and the underlying mechanisms in a mouse model. Our results showed that NKT pretreatment at the doses of 5, 10, and 20 mg/kg per day for 7 days significantly attenuates carbon tetrachloride (CCl4)-induced increases of serum BUN and CRE and kidney pathology injury. NKT pretreatment also markedly inhibited oxidative stress, inflammatory response, and the activation of caspases-9 and -3 in kidneys of mice exposed to CCl4. Meanwhile, NKT pretreatment downregulated the expression of NOX4, IL-1β, IL-6, and TNF-α proteins and NO levels in the kidney tissues. Moreover, NKT pretreatment upregulated the expression of Nrf2 and HO-1 mRNAs, and downregulated the expression of NF-κB, IL-1β, IL-6, TNF-α, and iNOS mRNAs in the kidneys of mice, compared to those in the CCl4alone treatment group. In conclusion, our results reveal that NKT supplementation could protect against CCl4exposure-induced oxidative stress and inflammatory response in the kidneys by inhibiting NOX4 and NF-κB pathways and activating the Nrf2/HO-1 pathway. Our current study highlights the therapeutic application of NKT for kidney diseases.Keywords:nootkatone;oxidative stress;nephrotoxicity;Nrf2/HO-1 pathway;NF-κB pathway

研究领域: 药理学 · 毒理学 · 分子生物学
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