JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2019
·Vol. 23
·期 3
·2174-2183
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IF 4.658
Haiman Mu,Haiwen Liu,Jiayi Zhang,Jianhua Huang,Chen Zhu,Yue Lu,Yueping Shi,Yi Wang
In addition to the known antitumour effects of ursolic acid (UA), increasing evidence indicates that this molecule plays a role in cardiac protection. In this study, the effects of ursolic acid on the heart in mice treated with doxorubicin (DOX) were assessed. The results showed that ursolic acid improved left ventrical fractional shortening (LVFS) and left ventrical ejection fraction (LVEF) of the heart, increased nitrogen oxide (NO) levels, inhibited reactive oxygen species (ROS) production and decreased cardiac apoptosis in mice treated with doxorubicin. Mechanistically, ursolic acid increased AKT and endothelial nitric-oxide synthase (eNOS) phosphorylation levels, and enhanced eNOS expression, while inhibiting doxorubicin induced eNOS uncoupling through NADPH oxidase 4 (NOX4) down-regulation. These effects of ursolic acid resulted in heart protection from doxorubicin-induced injury. Therefore, ursolic acid may be considered a potential therapeutic agent for doxorubicin-associated cardiac toxicity in clinical practice.
研究领域:
药理学
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心脏病学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF CELLULAR BIOCHEMISTRY
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2019
·Vol. 120
·期 10
·18509-18523
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IF 3.448
Yujie Yao,Xueyuan Hu,Xiujing Feng,Yuan Zhao,Manyu Song,Chaoran Wang,Honggang Fan
Dexmedetomidine (DEX) prevents kidney damage caused by sepsis, but the mechanism of this effect remains unclear. In this study, the protective molecular mechanism of DEX in lipopolysaccharide (LPS)-induced acute kidney injury was investigated and its potential pharmacological targets from the perspective of inhibiting oxidative stress damage and the nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome activation. Intraperitoneal injection of DEX (30 μg/kg) significantly improved LPS (10 mg/kg) induced renal pathological damage and renal dysfunction. DEX also ameliorated oxidative stress damage by reducing the contents of reactive oxygen species, malondialdehyde and hydrogen peroxide, and increasing the level of glutathione, as well as the activity of superoxide dismutase and catalase. In addition, DEX prevented nuclear factor-kappa B (NF-κB) activation and I-kappa B (IκB) phosphorylation, as well as the expressions of NLRP3 inflammasome-associated protein and downstream IL-18 and IL-1β. The messengerRNA (mRNA) and protein expressions of toll-like receptor 4 (TLR4), NADPH oxidase-4 (NOX4), NF-κB, and NLRP3 were also significantly reduced by DEX. Their expressions were further evaluated by immunohistochemistry, yielding results were consistent with the results of mRNA and protein detection. Interestingly, the protective effects of DEX were reversed by atipamezole-an alpha 2 adrenal receptor (α 2 AR) inhibitor, whereas idazoxan-an imidazoline receptor (IR) inhibitor failed to reverse this change. In conclusion, DEX attenuated LPS-induced AKI by inhibiting oxidative stress damage and NLRP3 inflammasome activation via regulating the TLR4/NOX4/NF-κB pathway, mainly acting on the α 2 AR rather than IR.
研究领域:
药理学
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免疫学
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肾脏生理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Liver Research
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2021
·
IF 0
Guizhi Yang,Shengwen Li,Jiahua Jin,Yuanyuan Xuan,Liqin Ding,Minxia Huang,Jun Liu,Biye Wang,Tian Lan
Background and aim Liver fibrosis resulting from persistent liver injury represents a major healthcare problem globally. Traditional Chinese medicine has played an essential role in the treatment of liver fibrosis in recent years. Thus, this study aims to assess the effect of Longhu Rendan (LHRD), a Chinese traditional patent medicine, on liver fibrosis and its potential mechanism. Methods The liver fibrosis in mice was induced via the intraperitoneal injection of carbon tetrachloride (CCl 4 ) for 6 weeks or bile duct ligation for 15 days. Various methods were used to judge the therapeutic effect of LHRD. Results LHRD significantly suppressed the activity of serum index of abnormal liver function, liver cell apoptosis, and necrosis, attenuating liver injury. Moreover, LHRD treatment alleviated liver fibrotic features, such as the reduction of collagen deposition and hepatic stellate cell activation as well as profibrotic gene expression. Mechanistically, LHRD treatment inhibited nuclear transcription factor-kappa B signaling and inflammatory gene expression and diminished the production of reactive oxygen species and 4-hydroxynonenal, along with the downregulation of NADPH oxidase 4. Conclusions Overall, the present study demonstrates that LHRD ameliorates liver injury and fibrosis via the inhibition of inflammation and oxidative stress in mice, indicating that LHRD is a potential medicine for the treatment of liver fibrosis.
研究领域:
药理学
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肝病学
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中医药
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DOI
Oxidative Medicine and Cellular Longevity
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2021
·
IF 6.543
Lijun Fang,Wei Wang,Jiazheng Chen,Anju Zuo,Hongmei Gao,Tao Yan,Pengqi Wang,Yujia Lu,Ruijuan Lv,Feng Xu,Yuguo Chen,Linmao Lyu
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease characterized by the extensive accumulation of myofibroblasts and collagens. However, the exact mechanism that underlies this condition is unclear. Growing evidence suggests that NADPH oxidases (NOXs), especially NOX4-derived oxidative stress, play an important role in the development of lung fibrosis. Bleomycin (BLM) is a tumor chemotherapeutic agent, which has been widely employed to establish IPF animal models. Osthole (OST) is an active constituent of the fruit of Cnidium ninidium. Here, we used an in vivo mouse model and found that OST suppressed BLM-induced body weight loss, lung injury, pulmonary index increase, fibroblast differentiation, and pulmonary fibrosis. OST also significantly downregulated BLM-induced NOX4 expression and oxidative stress in the lungs. In vitro, OST could inhibit TGF-β1-induced Smad3 phosphorylation, differentiation, proliferation, collagen synthesis, NOX4 expression, and ROS generation in human lung fibroblasts in a concentration-dependent manner. Moreover, NOX4 overexpression could prevent the above effects of OST. We came to the conclusion that OST could significantly attenuate BLM-induced pulmonary fibrosis in mice, via the mechanism that involved downregulating TGF-β1/NOX4-mediated oxidative stress in lung fibroblasts.
研究领域:
药理学
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呼吸病学
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分子生物学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Cell and Bioscience
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2024
·Vol. 14
·期 1
·1-18
·
IF 6.1
Maimaiti Yasenjiang,Su Ting,Zhang Zhanying,Ma Lingling,Zhang Yuan,Xu Hong
This study investigates NADPH oxidase 4 (NOX4) involvement in iron-mediated astrocyte cell death in Alzheimer’s Disease (AD) using single-cell sequencing data and transcriptomes. We analyzed AD single-cell RNA sequencing data, identified astrocyte marker genes, and explored biological processes in astrocytes. We integrated AD-related chip data with ferroptosis-related genes, highlighting NOX4. We validated NOX4’s role in ferroptosis and AD in vitro and in vivo. Astrocyte marker genes were enriched in AD, emphasizing their role. NOX4 emerged as a crucial player in astrocytic ferroptosis in AD. Silencing NOX4 mitigated ferroptosis, improved cognition, reduced Aβ and p-Tau levels, and alleviated mitochondrial abnormalities. NOX4 promotes astrocytic ferroptosis, underscoring its significance in AD progression.
研究领域:
神经科学
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分子生物学
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基因组学
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神经退行性疾病
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产品关联
DOI
PubMed
高影响因子
Current Research in Food Science
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2022
·
IF 6.269
Xuan Chen,Liufeng Zheng,Bing Zhang,Zeyuan Deng,Hongyan Li
Oxidative stress is a potential factor in the promotion of endothelial dysfunction. In this research, flavonoids (quercetin, luteolin) combined with carotenoids (lycopene, lutein), especially quercetin-lycopene combination (molar ratio 5:1), prevented the oxidative stress in HUVEC cells by reducing the reactive oxygen species (ROS) and suppressing the expression of NADPH oxidase 4 (Nox4), a major source of ROS production. RNA-seq analysis indicated quercetin-lycopene combination downregulated inflammatory genes induced by H 2 O 2 , such as IL-17 and NF-κB. The expression of NF-κB p65 was activated by H 2 O 2 but inhibited by the quercetin-lycopene combination. Moreover, the quercetin and lycopene combination promoted the thermostability of Sirtuin 1 (SIRT1) and activated SIRT1 deacetyl activity. SIRT1 inhibitor EX-527 attenuated the inhibitory effects of quercetin, lycopene, and their combination on the expression of p65, Nox4 enzyme, and ROS. Quercetin-lycopene combination could interact with SIRT1 to inhibit Nox4 and prevent endothelial oxidative stress, potentially contributing to the prevention of cardiovascular disease.
研究领域:
药理学
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分子生物学
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细胞生物学
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心血管研究
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产品关联
DOI
PubMed
高影响因子
Bioengineered
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2021
·
IF 3.269
Jihui Zhang,Hongwei Lei,Xiu Li
Gout is a common and complex form of arthritis that has brought great inconveniences to the normal lives of patients. It is reported that oxidative stress and nod-like receptor family protein 3 (NLRP3) inflammasome-mediated inflammatory reactions are involved in the pathogenesis of gout arthritis. S14G-humanin (S14G-HNG) is a modified peptide of HNG with higher inhibitory activity on the accumulation and deposition of Aβ. Recently, S14G-HNG has been reported to exert great anti-inflammatory effects. The present study proposed to explore the possible therapeutic property of S14G-HNG against gout arthritis. An animal model was established by stimulation with mono-sodium urate (MSU) crystals, followed by treatment with colchicine and S14G-HNG, respectively. The elevated Gait score promoted synovitis score and activated myeloperoxidase (MPO) observed in MSU crystals-treated mice were significantly reversed by colchicine and S14G-HNG. Bone marrow-derived macrophages (BMDMs) were isolated from mice and stimulated with MSU crystals, followed by being treated with 25 and 50 μM S14G-HNG. The increased mitochondrial reactive oxygen species (ROS) and Malondialdehyde (MDA) levels, upregulated NADPH oxidase-4 (NOX-4), activated NLRP3 inflammasome, and elevated production of inflammatory factors in MSU crystals-treated BMDMs were dramatically reversed by S14G-HNG, accompanied by the upregulation of sirtuin type-1 (SIRT1). Lastly, the protective effects of S14G-HNG against MSU crystals-induced NLRP3 inflammasome activation were significantly abolished by the knockdown of SIRT1. In conclusion, our data reveal that S14G-HNG could possess potential benefits against MSU crystals-induced gout arthritis, with colchicine displaying a better effect.
研究领域:
药理学
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免疫学
·
风湿病学
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产品关联
DOI
PubMed
高影响因子
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