FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Xiaowen Liu,Huamei Cai,Liang Peng,Hongli Ma,Yun Yan,Weixia Li,Jing Zhao
Remifentanil-induced hyperalgesia (RIH) represents a significant clinical challenge due to the widespread use of opioids in pain management. However, the molecular and cellular mechanisms underlying RIH remain elusive. This study aimed to unravel the role of spinal cord microglia, focusing on the Nrf2/HO-1 signaling pathway and TRPV4 channels in the development of RIH. We used both in vivo and in vitro models to investigate the activation state of spinal cord microglia, the expression of TRPV4 channels, and the modulation of the Nrf2/HO-1 pathway under remifentanil exposure. In addition, we evaluated the potential therapeutic effects of dexmedetomidine, a perioperative α2-adrenergic agonist, on RIH and its related molecular pathways. Our results revealed a prominent role of spinal cord microglia in RIH, demonstrating an apparent microglial M1 polarization and increased TRPV4 channel expression. A notable observation was the downregulation of the Nrf2/HO-1 pathway, which was associated with increased neuroinflammation and mechanical allodynia. By upregulating or overexpressing Nrf2, we confirmed its ability to inhibit TRPV4 and thereby attenuate RIH-associated mechanical allodynia, M1 polarization, and neuroinflammation. Encouragingly, dexmedetomidine demonstrated therapeutic potential by positively modulating the Nrf2-TRPV4 nexus, attenuating mechanical allodynia, and reducing microglial inflammation. Our research highlights the critical role of spinal cord microglia in RIH mediated by the Nrf2-TRPV4 axis. The ability of dexmedetomidine to modulate this axis suggests its potential as an adjunctive therapy to remifentanil in mitigating RIH. Further studies are imperative to explore the broader implications and practical applicability of our findings.
研究领域:
疼痛管理
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神经科学
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药理学
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炎症生物学
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DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS APPLICATIONS
·
2023
·
IF 2.9
Mengyu Zhu,Yang Zhang,Chi Zhang,Lei Chen,Ying Kuang
Oxidative damage of neurons is one of the key pathological markers of Alzheimer’s disease (AD), which eventually leads to neuronal apoptosis and loss. Nuclear factor E2-related factor 2 (Nrf2) is a key regulator of antioxidant response and is considered to be an important therapeutic target for neurodegenerative diseases. In this study, the selenated derivative of antioxidant rutin (Se-Rutin) was synthesized with sodium selenate (Na2SeO3) as raw material by a simple electrostatic-compound in situ selenium reduction method. The effects of Se-Rutin on H2O2 induced oxidative damage in Pheochromocytoma PC12 cells were evaluated by cell viability, apoptosis, reactive oxygen species level and the expression of antioxidant response element (Nrf2). The results showed that H2O2 treatment significantly increased the level of apoptosis and reactive oxygen species, while the level of Nrf2 and HO-1 decreased. However, Se-Rutin significantly reduced H2O2 induced apoptosis and cytotoxicity, and increased the expression of Nrf2 and HO-1, both of which were better than that of pure rutin. Therefore, the activation of Nrf2/HO-1 signaling pathway may be the basis of Se-Rutin’s anti-oxidative damage to AD.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Aging-US
·
2024
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IF 3.9
Xiao-Xiao Jiang,Ri Zhang,Hui-Shan Wang
Background: Atrial fibrillation (AF) is often associated with atrial fibrosis and oxidative stress. Neferine, a bisbenzylisoquinoline alkaloid, has been reported to exert an antiarrhythmic effect. However, its impact on Angiotensin II (Ang II) infusion-induced AF and the underlying mechanism remains unclear. This study aimed to investigate whether neferine alleviates Ang II-induced AF and explore the underlying mechanisms. Methods: Mice subjected to Ang II infusion to induce AF were concurrently treated with neferine or saline. AF incidence, myocardial cell size, fibrosis, and oxidative stress were then examined. Results: Neferine treatment inhibited Ang II-induced AF, atrial size augmentation, and atrial fibrosis. Additionally, we observed that Ang II increased reactive oxygen species (ROS) generation, induced mitochondrial membrane potential depolarization, and reduced glutathione (GSH) and superoxide dismutase (SOD) levels, which were reversed to some extent by neferine. Mechanistically, neferine activated the Nrf2/HO-1 signaling pathway and inhibited TGF-β/p-Smad2/3 in Ang II-infused atria. Zinc Protoporphyrin (ZnPP), an HO-1 inhibitor, reduced the anti-oxidative effect of neferine to some extent and subsequently abolished the beneficial effect of neferine on Ang II-induced AF. Conclusions: These findings provide hitherto undocumented evidence that the protective role of neferine in Ang II-induced AF is dependent on HO-1.
研究领域:
心脏病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2021
·Vol. 18
·期 4
·e2001007
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IF 2.408
Yan Zhao,Yu Wang,Min Zhang,Yugang Gao,Zhaowei Yan
Ginsenosides (20 S )-Rg3 and (20 R )-Rg3 are famous rare ginsenosides from red ginseng, and their configurations in C-20 are different. This study aimed to investigate the protective mechanism of ginsenosides (20 S )-Rg3 and (20 R )-Rg3 on H 2 O 2 -induced H9C2 cells and compare their activity. The results showed that the ginsenosides (20 S )-Rg3 and (20 R )-Rg3 could increase the cell activity and the levels of GSH-Px, SOD and CAT, and decrease activities of LDH, MDA and ROS. Further studies showed that ginsenosides (20 S )-Rg3 and (20 R )-Rg3 could prevent oxidative stress injury of H9C2 cells by H 2 O 2 through the Keap-1/Nrf2/HO-1 pathway. But the ML385 counteracts these effects. Interestingly, among these results, ginsenoside (20 R )-Rg3 was superior to (20 S )-Rg3, indicating that ginsenoside (20 R )-Rg3 have a stronger effect of antioxidative stress. This study reflected that ginsenoside (20 R )-Rg3 could be used as a potential Nrf2 activator and a safe effective Chinese herbal monomer in the treatment of cardiovascular disease.
研究领域:
药理学
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心脏病学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
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IF 4.7
Man Zheng,Fenglei Zhang,Xiang Gong,Haitao Yuan
The oxidative damage to vascular endothelial cells induced by smoking represents a significant pathogenic factor in the development of atherosclerosis. In the present study, we isolated ginseng oligopeptide extract (GOE), which emerges as a promising candidate for protecting human aortic endothelial cells (HAECs) from nicotine-induced oxidative stress. The underlying mechanisms were also explored. The GOE effectively reversed the decline in cell viability and protected HAECs from nicotine-induced oxidative damage by inhibiting the overproduction of intracellular reactive oxygen species (ROS) while preserving superoxide dismutase (SOD) activity. We identified five ginseng oligopeptides (GOPs) as the primary components of GOE. Furthermore, we demonstrated that GOE significantly alleviated nicotine-induced mitochondrial dysfunction in HAECs while promoting the nitric oxide (NO) release and the expression of GTP cyclohydrolase 1 (GTPCH1). Although the precise mechanism through which GOE mitigates nicotine-induced oxidative stress in HAECs remains to be fully elucidated, our findings indicate that GOP-1–5 serve as bioactive constituents of GOE and play a significant synergistic role in reducing nicotine-induced apoptosis and oxidative damages in HAECs. This is achieved through modulation of cellular antioxidant systems via maintaining balance within the Keap1/Nrf2/HO-1 signaling pathway. These findings suggest that GOE may function as a potential therapeutic agent against cigarette smoking-induced atherosclerosis.
研究领域:
心血管生物学
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药理学
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DOI
PubMed
高影响因子
RSC Advances
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2017
·Vol. 7
·期 55
·34846-34856
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IF 3.108
Ye Tian,Zheng Li,Bingyu Shen,Lin Wu,Lu Han,Qiaoling Zhang,Haihua Feng
Shikonin (SHK) has various biological and pharmacological activities, including anticancer, antibacterial and anti-inflammation activities. However, the protective effects and mechanism of SHK on lipopolysaccharide (LPS) and D-galactosamine (D-GalN) induced acute liver injury remain unclear. In this study, LPS/D-GalN caused acute liver injury by intraperitoneal injection. SHK was administrated for 1 h. Then, LPS/D-GalN was given to C57BL/6 mice for 3 h. Our results showed that SHK treatment distinctly decreased serum TNF-α, IL-1β, IL-6 and IFN-γ inflammatory cytokine production, reduced serum ALT, AST, hepatic MPO and ROS production levels, and tissue histology harmful effects, inhibited JNK1/2, ERK1/2, p38 and NF-κB (p65) phosphorylation, and suppressed IκBα phosphorylation and degradation. Furthermore, our research showed that SHK could dramatically increase SOD and GSH production, as well as reduce ROS production, through up-regulating the protein expression of HO-1, Nqo1, Gclc and Gclm, which was related to the induction of Nrf2 nuclear translocation. These results showed that SHK exerted anti-inflammatory activity, which was associated to the inhibition of inflammatory production via down-regulation of the MAPK and NF-κB signaling pathways, and anti-oxidative effects were connected with GSH and SOD activation through up-regulation of the Nrf2/HO-1 signaling pathways.
研究领域:
药理学
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肝病学
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免疫学
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分子生物学
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DOI
高影响因子
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
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2021
·Vol. 99
·期 12
·
IF 2.273
Weimin Xu,Peng Wang,Dalong Wang,Ke Liu,Shuaishuai Zhang,Wei Zhao,Guoqing Liu
The aim of the present study was to investigate the protective effect of S-ketamine (S-KET) against carbon tetrachloride (CCl4) – induced liver damage and oxidative stress, as well as to elucidate the related underlying mechanisms. Blood was collected to measure biochemical parameters (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TB) and γ-glutamyltransferase (γ-GT)) and the liver was harvested for histopathological analysis of enzymes related to the antioxidant response (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX)). Liver cell apoptosis was evaluated using the TUNEL assay. In addition, the expression levels of apoptosis-related proteins and the nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway were detected by Western blot analysis to explore potential mechanisms. S-KET protected the liver from CCl4-induced damage. The changes to the liver biochemical parameters (increased ALT, AST, ALP, TB, and γ-GT) and oxidative stress-related indicators (increased MDA; depleted SOD, GSH, and GSH-PX) induced by CCl4 were inhibited by S-KET. S-Ket also inhibited CCl4-induced cell apoptosis, the changes in expression of related proteins, and blocked CCl4-induced liver injury and oxidative stress via activation of the Nrf2/HO-1 signaling pathway. S-KET effectively protected the liver by inhibition of CCl4-induced damage via upregulation the Nrf2/HO-1 signaling pathway.
研究领域:
药理学
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肝病学
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分子生物学
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毒理学
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DOI
PubMed
高影响因子
ACS Nano
·
2024
·
IF 15.8
Xirui Xin,Junjun Liu,Xinchan Liu,Yu Xin,Yubo Hou,Xingchen Xiang,Yu Deng,Bai Yang,Weixian Yu
Periodontitis is a chronic inflammatory disease closely associated with reactive oxygen species (ROS) involvement. Eliminating ROS to control the periodontal microenvironment and alleviate the inflammatory response could potentially serve as an efficacious therapy for periodontitis. Melatonin (MT), renowned for its potent antioxidant and anti-inflammatory characteristics, is frequently employed as an ROS scavenger in inflammatory diseases. However, the therapeutic efficacy of MT remains unsatisfactory due to the low water solubility and poor bioavailability. Carbon dots have emerged as a promising and innovative nanomaterial with facile synthesis, environmental friendliness, and low cost. In this study, melatonin-derived carbon dots (MT-CDs) were successfully synthesized via the hydrothermal method. The MT-CDs have good water solubility and biocompatibility and feature excellent ROS-scavenging capacity without additional modification. The in vitro experiments proved that MT-CDs efficiently regulated intracellular ROS, which maintained mitochondrial homeostasis and suppressed the production of inflammatory mediators. Furthermore, findings from the mouse model of periodontitis indicated that MT-CDs significantly inhibited the deterioration of alveolar bone and reduced osteoclast activation and inflammation, thereby contributing to the regeneration of damaged tissue. In terms of the mechanism, MT-CDs may scavenge ROS, thereby preventing cellular damage and the production of inflammatory factors by regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. The findings will offer a vital understanding of the advancement of secure and effective ROS-scavenging platforms for more biomedical applications.
研究领域:
纳米技术
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药学
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牙科医学
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分子生物学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2023
·Vol. 12
·期 1
·194
·
IF 7
Chongshan Dai,Xueyong Zhang,Jiahao Lin,Jianzhong Shen
Acute liver injury is a type of liver diseases, and it has raised concerns worldwide due to the lack of effective therapies. The aim of this study is to investigate the protective effects of nootkatone (NOOT) on carbon tetrachloride (CCl4)-caused acute liver injury in mice. Mice were randomly divided into control, CCl4model, NOOT, and NOOT (5, 10, and 20 mg/kg/day) plus CCl4groups, respectively. Mice in the CCl4plus NOOT groups were orally administrated with NOOT at 5, 10, and 20 mg/kg/days for seven days prior to 0.3% CCl4injection at 10 mL/kg body weight, respectively. Our results showed that NOOT supplementation significantly ameliorated CCl4-induced increases of serum AST and ALT levels, hepatocyte necrosis, inflammatory response, oxidative stress, and caspases-9 and -3 activities in the livers of mice. Moreover, NOOT supplementation significantly upregulated the expression of Nrf2 and HO-1 mRNAs but downregulated the expression of NF-κB mRNAs and the levels of IL-1β, IL-6, and TNF-α proteins in the liver tissues, compared to those in the CCl4model group. In conclusion, for the first time, our results reveal that NOOT could offer protective effects against CCl4-caused oxidative stress and inflammatory response via the opposite regulation of Nrf2/HO-1 pathway and NF-κB pathway.Keywords:nootkatone;oxidative stress;acute liver injury;Nrf2/HO-1 pathway;NF-κB pathway
研究领域:
药理学
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肝病学
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分子生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 11
·1296
·
IF 6
Yue Liu,Chunhong Chen,Zhihui Hao,Jianzhong Shen,Shusheng Tang,Chongshan Dai
Exposure to cadmium sulfate (CdSO4) can lead to neurotoxicity. Nevertheless, the precise molecular mechanisms underlying this phenomenon remain unclear, and effective treatment strategies are scarce. This study explored the protective effects of ellagic acid (EA), a natural polyphenolic compound, against CdSO4exposure-induced neurotoxicity in HT22 cells and the underlying molecular mechanisms. Our findings demonstrated that exposure of HT22 cells to CdSO4resulted in apoptosis, which was effectively reversed by EA in a dose-dependent manner. EA supplementation also decreased reactive oxygen species (ROS) and mitochondrial ROS production, reduced malondialdehyde (MDA) levels, and restored the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, EA supplementation at 5–20 μM significantly counteracted Cd-induced the loss of mitochondrial membrane potential and the decrease of ATP and reduced the ratio of Bax/Bcl-2 and cleaved-caspase-3 protein expression. Furthermore, EA supplementation resulted in the upregulation of Nrf2 and HO-1 protein and mRNAs while simultaneously downregulating the phosphorylation of JNK and p38 proteins. The pharmacological inhibition of c-Jun N-terminal kinase (JNK) partially attenuated the activation of the Nrf2/HO-1 pathway induced by CdSO4and exacerbated its cytotoxic effects. In conclusion, our findings suggest that ethyl acetate (EA) supplementation offers protective effects against CdSO4-induced apoptosis in HT22 cells by inhibiting oxidative stress and activating the Nrf2 signaling pathway. Furthermore, the activation of the JNK pathway appears to play a protective role in CdSO4-induced apoptosis in HT22 cells.
研究领域:
毒理学
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药理学
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细胞生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
·Vol. 10
·期 2
·e24339
·
IF 3.4
Suqin Yang,Gang Liu,Xiankun Xia,Dali Gan,Shijian Xiang,Meixian Xiang
α-Mangostin is a natural xanthone derivative isolated from Camellia atrophy (CA), commonly known as Lichuan black tea (LBT). The present study investigated the ameliorating effect and mechanism of α-mangostin on alcoholic gastric ulcers (GU) in rats. In vivo , α-mangostin relieved pathological symptoms. Moreover, α-mangostin regulated the activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/heme oxygenase 1 (HO-1) and nuclear factor κB (NF-κB)/NLR family pyrin domain containing 3 (NLRP3)/caspase-1 pathways. Reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) were significantly decreased and IL-10 were increased, the microtubule-associated protein light chain 3 (LC3)-II/LC3-I ratio was increased, p62 protein expression was decreased, and inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expression was down-regulated. The relevant mechanisms were validated using GSE-1 and RAW264.7 cells in an in vitro model. Furthermore, α-mangostin increased Ligilactobacillus and Muribaculum abundance as well as propionic acid and butyric acid contents. Therefore, α-mangostin possesses antioxidant and anti-inflammatory properties, and remodels intestinal flora dysbiosis through mechanisms that may involve regulation of the Nrf2/HO-1 pathway and NF-κB/NLRP3/caspase-1 pathway. It also increases propionic acid and butyric acid contents. This study provides novel evidence regarding the use of α-mangostin for treating GU.
研究领域:
药理学
·
胃肠病学
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微生物学
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产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2024
·
IF 4.7
Xiaona Lang,Liyan Xu,Lu Li,Xin Feng
Objective Catalpol, as a natural medicine small-molecule drug, has been proven to have anti-inflammatory and antioxidant pharmacological effects.Methods The effect of catalpol on oxidative damage of mouse epidermal fibroblast L929 model and its mechanism were investigated by using hydrogen peroxide model, CCK8 method, flow cytometry, and Western blot.Results The effect of catalpol on Nrf2/HO-1 signaling pathway was further studied to improve oxidative stress in cell models. The results showed that catalpol had no cytotoxicity to L929 cells, and inhibited the apoptosis of L929 cells after oxidative damage in a concentration-dependent manner, thus playing a role in cell protection. The oxidative damage of cells was inhibited by up-regulating the expression of the signature protein of Nrf2/HO-1 signaling pathway and inhibiting the interstitial formation of cells.Conclusion This study is a preliminary study on the protective function of catalpol against oxidation and apoptosis in dermal fibroblasts, which can provide a theoretical basis and drug guidance for promoting skin wound healing in the later stage.
研究领域:
药理学
·
细胞生物学
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分子生物学
·
皮肤伤口愈合
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DOI
PubMed
高影响因子
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