CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 43
·期 4
·1359-1368
·
IF 5.104
Du Lifen,Lei Yongfang,Chen Jinglou,Song Hongping,Wu Xinying
Background/Aims: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Method: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. Results: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. Conclusion: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways
研究领域:
药理学
·
毒理学
·
分子生物学
·
生殖医学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NEUROTRAUMA
·
2023
·
IF 4.2
Hongxing Tang,Kejun He,Kun Zhao,Chen Zheng,Weichi Wu,Weilin Jin,Lixuan Yang,Baoshu Xie
Hinokitiol (β-thujaplicin, HIK) is a natural monoterpene small molecule compound showing various biological effects including antibacterial, anti- inflammatory and anti-tumor. Ferroptosis, a new form of iron-dependent cell death, has been demonstrated as one of the pathophysiological mechanisms of traumatic brain injury (TBI). However, the effect of hinokitiol on neuronal ferroptosis after traumatic brain injury has not been reported. Here, we show that hinokitiol alleviated excessive glutamate-induced intracellular reactive oxygen species (ROS), lipid peroxidation, and Fe2+ accumulation in HT-22. Moreover, hinokitiol upregulated heme oxygenase-1 (HO-1) expression, promoted nuclear factor-erythroid factor 2-related factor 2 (Nrf2) nuclear translocation, and inhibited the activation of microglia and astrocyte after TBI. Furthermore, hinokitiol remarkably reduced brain tissue lesions, mitigated neuron loss, iron deposition and attenuated neurologic impairment in the CCI-constructed TBI model in vivo. These results suggest that hinokitiol has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. In summary, we reveal a novel role of hinokitiol in TBI, which has neuroprotective effects on rescuing cells from TBI-induced neuronal ferroptosis. Moreover, hinokitiol through activating the Nrf2/Keap1/HO-1 signaling pathway significantly reduces the neuronal damage, suggesting that it is a potential therapeutic candidate for TBI.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
AMB Express
·
2024
·Vol. 14
·期 1
·1-16
·
IF 3.5
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.
研究领域:
药理学
·
肝病学
·
营养学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
·
2022
·
IF 4.369
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 .
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
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2019
·
IF 3.407
Li-Ming Yu,Xue Dong,Xiao-Dong Xue,Jian Zhang,Zhi Li,Hong-Jiang Wu,Zhong-Lu Yang,Yang Yang,Hui-Shan Wang
Punicalagin has been found to exert cardiac protective effects against myocardial ischemia/reperfusion (MI/R) injury, although the detailed mechanisms remain largely unknown. This experiment was performed to explore the potential involvement of silent information regulator 1 (SIRT1)-NFE2-related factor 2 (NRF-2)-heme oxygenase-1 (HO-1) pathway in the cardiac protective actions of punicalagin. Sprague-Dawley (SD) rats were subjected to MI/R operation with or without punicalagin treatment (40 mg kg −1 d −1 ). We showed that punicalagin-treated group exhibited enhanced cardiac function, reduced myocardial infarction and decreased cleaved caspase-3 level. Furthermore, myocardial oxidative/nitrosative stress was ameliorated by punicalagin as evidenced by suppressed superoxide generation, gp91 phox and iNOS expressions, NO metabolites as well as myocardial nitrotyrosine level. Additionally, punicalagin decreased myocardial IL-6, TNF-α and the levels of ICAM-1, VCAM-1 and IKK-β expressions as well as IκB-α phosphorylation and NF-κB nuclear translocation. However, these effects were abolished by EX527 (5 mg kg −1 d −1 , a selective SIRT1 inhibitor). We further found that punicalagin dose-dependently enhanced SIRT1 nuclear distribution and NRF-2-HO-1 signaling. While EX527 treatment not only reduced SIRT1 activity, but also reversed the activation of NRF-2-HO-1 pathway. Collectively, these results revealed that punicalagin reduced cardiac oxidative/nitrosative stress and inflammatory response induced by MI/R operation through SIRT1-mediated activation of NRF-2-HO-1 signaling.
研究领域:
心脏病学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Marine Drugs
·
2025
·Vol. 23
·期 3
·134
·
IF 5.4
Yanglong Liu,Jiawei Sun,Qihao Yan,Bingjian Wen,Yan Bai,Qishi Che,Hua Cao,Jiao Guo,Zhengquan Su
Alcoholic liver disease (ALD) is a liver disorder resulting from excessive alcohol intake, and currently, there are no therapeutics approved by the FDA for its treatment. This study investigates the protective effects and underlying pharmacological mechanisms of two chitosan oligosaccharides, COST (MW ≤ 1000 Da) and COSM (MW ≤ 3000 Da), in mitigating alcohol-induced liver disease (ALD). In animal models, we evaluated the changes in ALD following treatment with COST and COSM. Histopathological analysis revealed that both COST and COSM interventions mitigated hepatic steatosis and inflammatory infiltration. Additionally, these compounds reduced various markers of liver injury, enhanced antioxidant enzyme levels, and significantly improved liver function. Western blot analysis demonstrated that COSM markedly decreased the expression of the hepatic metabolic enzyme CYP2E1, activated the Keap-1/Nrf-2/HO-1 pathway, and restrained the NF-κB and MAPK pathways. In an in vitro model of alcohol-induced hepatocyte L02 injury, both COST and COSM exhibited protective effects on hepatocytes, corroborating the findings from the animal studies. Collectively, in vivo and in vitro experiments confirmed that COST and COSM can reduce oxidative damage, enhance antioxidant capacity, and ameliorate steatosis and inflammatory damage in the liver, thereby significantly attenuating alcohol-induced injury. Notably, COSM exhibited slightly superior efficacy compared to COST.
研究领域:
药理学
·
肝脏病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARDIOVASCULAR DRUGS AND THERAPY
·
2023
·
IF 3.4
Zhang Lingxi,Hu Chenghong,Jin Bo,Bai Bin,Liao Jing,Jin Leiming,Wang Minxiu,Zhu Weiwei,Wu Xuedan,Zheng Li,Xu Xuelian,Jiang Yongsheng,Wang Yi,He Ying
Purpose Diabetic cardiomyopathy (DCM) is a common and severe complication of diabetes. Inflammation and oxidative stress play important roles in DCM development. Bicyclol is a hepatoprotective drug in China that exerts anti-inflammatory effects by inhibiting the MAPK and NF-κB pathways to prevent obesity-induced cardiomyopathy. Our purpose was to explore the effect and mechanism of bicyclol on DCM. Methods A type 1 diabetes mouse model was established using C57BL/6 mice by intraperitoneal injection of STZ. The therapeutic effect of bicyclol was evaluated in both heart tissues of diabetic mice and high concentration of glucose (HG)-stimulated H9c2 cells. Results We showed that bicyclol significantly attenuated diabetes-induced cardiac hypertrophy and fibrosis, which is accompanied by the preservation of cardiac function in mice. In addition, bicyclol exhibited anti-inflammatory and anti-oxidative effects both in vitro and in vivo. Furthermore, bicyclol inhibited the hyperglycemia-induced activation of MAPKs and NF-κB pathways, while upregulating the Nrf-2/HO-1 pathway to exhibit protective effects. Conclusion Our data indicate that bicyclol could be a promising cardioprotective agent in the treatment of DCM.
研究领域:
药理学
·
心脏病学
·
糖尿病研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
·
2024
·
IF 5.6
Hu Xu,Gen Li,Cheng Wan,Xiao-Yi Wei,Tao Zhou
In order to improve the extraction yield of lotus leaf polysaccharide (LLP) and offer scientific foundation for utilization of LLPs in the food and pharmaceutical industries, pectinase-assisted extraction method was employed for the preparation of LLP. The chemical composition, physicochemical properties (e.g. rheological and thermal properties etc.), antioxidant and anti-inflammatory effects of LLP and its two purified fractions (LLP1 and LLP3) obtained using DEAE-52 and subsequent Sephadex G-100 column chromatography were also investigated. Antioxidant assays indicated that the polysaccharides had remarkable DPPH• and ABTS +• scavenging activities. In H 2 O 2 -induced RAW264.7 cells, LLPs showed marked protective effect on oxidative stress, reducing the MDA and ROS contents and increasing the CAT and SOD activities. LLPs were also found to effectively modulate the expressions of CAT, SOD1, Nrf-2, HO-1, NQO1 and Keap1 mRNA. Thus, the potent antioxidant effects of LLPs were achieved possibly by regulating the Keap1/Nrf-2/HO-1 signaling pathways. In lipopolysaccharide-treated RAW264.7 macrophages, LLPs reduced phagocytic ability, decreased release of NO, TNF-α, IL-1β and IL-6, and increased release of IL-10 and TGF-β1, indicating their potent anti-inflammatory effect. LLPs downregulated expressions of iNOS, IL-1β, IL-6, TNF-α, COX-2, and TLR-4 mRNA. Therefore, modulation of NF-κB signaling pathway is possibly the important anti-inflammatory mechanism of LLPs.
研究领域:
食品科学
·
药理学
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Yanan Wang,Xiaohu Liu,Keyang Li,Xinyuan Wang,Xue Zhang,Deyao Qian,Xinlei Meng,Liangmin Yu,Xuefeng Yan,Zhiyu He
Exogenous polysulfhydryls (R-SH) supplementation and nitric oxide (NO) gas molecules delivery provide essential antioxidant buffering pool components and anti-inflammatory species in cellular defense against injury, respectively. Herein, the intermolecular disulfide bonds in bovine serum albumin (BSA) molecules were reductively cleaved under native and mild conditions to expose multiple sulfhydryl groups (BSA-SH), then sulfhydryl-nitrosylated (R-SNO), and nanoprecipitated to form injectable self-sulfhydrated, nitro-fixed albumin nanoparticles (BSA-SNO NPs), allowing albumin to act as a NO donor reservoir and multiple sulfhydryl group transporter while also preventing unfavorable oxidation and self-cross-linking of polysulfhydryl groups. In two mouse models of ischemia/reperfusion-induced and endotoxin-induced acute liver injury (ALI), a single low dosage of BSA-SNO NPs (S-nitrosothiols: 4 μmol·kg–1) effectively attenuated oxidative stress and systemic inflammation cascades in the upstream pathophysiology of disease progression, thus rescuing dying hepatocytes, regulating host defense, repairing microcirculation, and restoring liver function. By mechanistically upregulating the antioxidative signaling pathway (Nrf-2/HO-1/NOQ1) and inhibiting the inflammatory cytokine storm (NF-κB/p-IκBα/TNF-α/IL-β), BSA-SNO NPs blocked the initiation of the mitochondrial apoptotic signaling pathway (Cyto C/Bcl-2 family/caspase-3) and downregulated the cell pyroptosis pathway (NLRP3/ASC/IL-1β), resulting in an increased survival rate from 26.7 to 73.3%. This self-sulfhydrated, nitro-fixed functionalized BSA nanoformulation proposes a potential drug-free treatment strategy for ALI.
研究领域:
药理学
·
纳米技术
·
肝病学
·
分子生物学
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）