BRITISH JOURNAL OF PHARMACOLOGY
·
2018
·Vol. 175
·期 16
·3315-3332
·
IF 6.81
Bo Wei,Qiao Lin,Ya-Ge Ji,Yi-Can Zhao,Li-Na Ding,Wen-Juan Zhou,Li-Hua Zhang,Chuan-Yu Gao,Wen Zhao
Background and Purpose Antioxidants provide a promising therapeutic effect for the cardiovascular disease. Luteolin, a polyphenolic bioflavonoid, is known to confer cardioprotection, although the underlying mechanisms, especially the role of luteolin on the antioxidant enzymes, such as the peroxiredoxin family, remain unknown. Experimental Approach We measured the effects of luteolin on myocardial ischaemia/reperfusion (MI/R) injury in vivo (Sprague-Dawley rats) and in vitro , together with the underlying mechanisms, with a focus on signalling by peroxiredoxins. H9c2 cells were used to assess the changes in peroxiredoxins and the other antioxidant enzymes. Oxidative stress, cardiac function, LDH release, ROS and infarct size were also assayed. Key Results Luteolin exerted significant cardioprotective effects in vivo and in vitro via improving cardiac function, increasing the expression of anti-apoptotic protein Bcl-2 and decreasing the pro-apoptotic protein Bax and active caspases 3 and 9, associated with MI/R. Mechanistically, luteolin markedly enhanced expression of peroxiredoxin II, without significant effects on other forms of peroxiredoxin, catalase or SOD1. Molecular docking showed that luteolin could indeed bind to the enzymic active pocket of peroxiredoxin II. Furthermore, down-regulation of peroxiredoxin II by peroxiredoxin II-antisense, administered by adenovirus infection of H9c2 cardiomyocytes, and inhibition of peroxiredoxin II in vivo significantly reversed the cardioprotective effects of luteolin. Conclusions and Implications Our findings, for the first time, demonstrate that luteolin protects against MI/R injury through promoting signalling through the endogenous antioxidant enzyme, peroxiredoxin II, indicating the important beneficial role of this antioxidant system in the heart.
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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生物化学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2020
·
IF 4.268
Rui Guo,Ningning Liu,Hao Liu,Junhua Zhang,Han Zhang,Yingchao Wang,Mirko Baruscotti,Lu Zhao,Yi Wang
Background : Cardiac hypertrophy is a prominent feature of heart remodeling, which may eventually lead to heart failure. Tongmaiyangxin (TMYX) pills are a clinically used botanical drug for treating multiple cardiovascular diseases including chronic heart failure. The aim of the current study was to identify the bioactive compounds in Tongmaiyangxin pills that attenuate cardiomyocytes hypertrophy, and to investigate the underlying mechanism of action. Methods and Results : The anti-hypertrophy effect of TMYX was validated in isoproterenol-induced cardiac hypertrophy model in C57BL/6 mice. After TMYX treatment for 2 weeks, the heart ejection fraction and fractional shortening of the mice model was increased by approximately 20% and 15%, respectively, ( p < 0.05). Besides, TMYX dose-dependently reduced the cross section area of cardiomyocytes in the angiotensin-II induced hypertrophy H9c2 model ( p < 0.01). Combining high content screening and liquid chromatography mass spectrometry, four compounds with anti-cardiac hypertrophy effects were identified from TMYX, which includes emodin, licoisoflavone A, licoricone and glyasperin A. Licoisoflavone A is one of the compounds with most significant protective effect and we continued to investigate the mechanism. Primary cultures of neonatal rat cardiomyocytes were treated with a hypertrophic agonist phenylephrine (PE) in the presence or absence of licoisoflavone A. After 48 h of treatment, cells were harvested and mitochondrial acetylation was analyzed by western blotting and Image analysis. Interestingly, the results suggested that the anti-hypertrophic effects of licoisoflavone A depend on the activation of the deacetylase Sirt3 ( p < 0.01). Finally, we showed that licoisoflavone A-treatment was able to decrease relative ANF and BNP levels in the hypertrophic cardiac cells ( p < 0.01), but not in cells co-treated with Sirt3 inhibitors (3-TYP) ( p > 0.05). Conclusion : TMYX exerts its anti-hypertrophy effect possibly through upregulating Sirt3 expression. Four compounds were identified from TMYX which may be responsible for the anti-hypertrophy effect. Among these compounds, licoisoflavone A was demonstrated to block the hypertrophic response of cardiomyocytes, which required its positive regulation on the expression of Sirt3. These results suggested that licoisoflavone A is a potential Sirt3 activator with therapeutic effect on cardiac hypertrophy.
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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中医
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2023
·
IF 8.2
Jie Liu,Xue Li,Jing-wen Guo,Bo-xue Chen,He Sun,Jia-qi Huang,Ying Hu,Xiao-yan Xu,Mei-ting Jiang,Xiu-mei Gao,Wen-zhi Yang,Qi-long Wang,De-an Guo
Ginseng is rich of polysaccharides, however, the evidence supporting polysaccharides to distinguish various ginseng species is rarely reported. Focusing on six root ginseng ( e.g. , Panax ginseng - PG , P. quinquefolius - PQ , P. notoginseng - PN , red ginseng- RG , P. japonicus - PJ , and P. japonicus var. major - PJM ), the contained non-starch polysaccharides (NPs) were structurally characterized and compared by both the chemical and biological evaluation. Holistic fingerprinting at three levels (the NPs and the acid hydrolysates involving oligosaccharides and monosaccharides) utilized various chromatography methods, and the treatment of H9c2 cells with the NPs by OGD and H 2 O 2 -induced injury models was used to assess the protective effect. NPs from six Panax herbal medicines occupied about 20 % of the total polysaccharides, which were of the highest content in RG and the lowest in PN. NPs from six ginseng exhibited weak differentiations in the molecular weight distribution, while marker oligosaccharides were found to distinguish PN and RG from the others. Glc and GalA were more abundant in the NPs for PG and RG, respectively. NPs from PQ (100/200 μg/mL) showed significant cardiomyocyte protection effect by regulating the mitochondrial functions. This work further testifies the role of polysaccharides in quality control of herbal medicine, with new markers discovered beneficial to distinguish the ginseng.
研究领域:
药理学
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生物化学
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药物化学
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中药学
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产品关联
DOI
PubMed
高影响因子
ARCHIVES OF TOXICOLOGY
·
2014
·Vol. 89
·期 3
·357-369
·
IF 5.078
Luo Cheng,Li Yan,Yang Liang,Wang Xun,Long Jiangang,Liu Jiankang
Superparamagnetic iron oxide nanoparticles (IONPs) have been widely applied in numerous biomedical fields. The evaluation of the toxicity of IONPs to the environment and human beings is indispensable to guide their applications. IONPs are usually considered to have good biocompatibility; however, some literatures have reported the toxicity of IONPs in vitro and in vivo. The controversy surrounding the biocompatibility of IONPs prompted us to carefully consider the biological effects of IONPs, especially under stress conditions. However, the potential risks of IONPs under stress conditions have not yet been evaluated in depth. Acrolein is widespread in the environment and modulates stress-induced gene activation and cell death in many organs and tissues. In this study, we assessed the sensitivity of H9c2 cardiomyocyte cells embedded with IONPs to acrolein and investigated the possible molecular mechanisms involved in this sensitivity. IONPs, which alone exhibited no toxicity, sensitized the H9c2 cardiomyocytes to acrolein-induced dysfunction. The IONP/acrolein treatment induced a loss of viability, membrane disruption, reactive oxygen species (ROS) generation, Erk activation, mitochondrial and lysosomal dysfunction, and necrosis in H9c2 cells. Treatment with an ROS generation inhibitor (diphenyleneiodonium) or an iron chelator (deferoxamine) prevented the IONP/acrolein-induced loss of viability, suggesting that ROS and IONP degradation facilitated the toxicity of the IONP/acrolein treatment in H9c2 cells. Our data suggest that cells embedded in IONPs are more vulnerable to oxidative stress, which confirms the hypothesis that nanoparticles can sensitize cells to the adverse effects of external stimulation. The present work provides a new perspective from which to evaluate the interactions between nanoparticles and cells.
研究领域:
纳米技术
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生物医学工程
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毒理学
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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
Biomaterials Science
·
2022
·Vol. 11
·期 3
·894-907
·
IF 7.59
Yiran Wang,Mingxi Yang,Jiayi Zhang,Jingyan Ren,Ning Liu,Bin Liu,Laijin Lu,Bai Yang
Myocardial fibrosis (MF) is a critical pathological lesion in the progression of various acute and chronic cardiovascular diseases. However, there is still a lack of clinically effective drugs and treatments for MF therapies. Herein, for the first time, we developed fluorescent sulfur-doped carbonized polymer dots (S-CPDs) as new nano-antioxidants to reduce the cardiomyocyte damage caused by reactive oxygen species (ROS) in the early stage of fibrotic lesions. In vitro results suggested that the pre-protection of S-CPDs significantly increased the survival rate of H9c2 cells under severe oxidative stress, inhibited the isoproterenol (ISO)-induced hypertrophy of myocardial cells through improving the content of mitochondria related proteins and adenosine triphosphate (ATP) in cells. Moreover, S-CPD administration could effectively decrease cardiac hypertrophy and promote heart function in MF rat models. The rapid internalization, high biocompatibility and fluorescence imaging potential of S-CPDs revealed their promising application prospects in the diagnoses and treatments of cardiovascular diseases.
研究领域:
纳米技术
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心血管疾病
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生物医学工程
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药理学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
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2020
·
IF 4.099
Xueli Lv,Yaolu Zhu,Yingguang Deng,Shichang Zhang,Qing Zhang,Boxin Zhao,Guofeng Li
Doxorubicin (DOX) is one of the most effective and irreplaceable chemotherapeutic agents but its clinical use is limited due to its cardiotoxicity. Glycyrrhizin(GL) has been applied to liver disorders for long. However, little is known that if GL could be meaningful in attenuating cardiotoxicity. The aim of this study is to investigate the cardioprotective effects of GL in DOX-induced cardiotoxicity (DIC) and the underlying mechanism. Here, H9c2 cardiomyoblasts, Neonatal rat cardiomyocytes (NRCMs), and Rats were introduced as test models. A single dose of 20 mg/kg DOX (i.p.) was applied to induce acute cardiotoxicity in vivo, as reflected by growth inhibition, increased levels of AST and CK-MB, and reduction of SOD activity, while GL (25 or 50 mg/kg/d, 14 d, i.p.) could counteract these effects. Moreover, pre-incubation with GL (0.8 mM for 12 h) in H9c2 cells protected against DOX-induced cytotoxicity, oxidative stress and depolarization of mitochondrial membrane potential (MMP). Besides, Western blot analysis showed that DOX upregulated the expression of LC3 II and p62 whereas GL reversed that both in vitro and in vivo and improved the obstructed autophagy flux in DOX-treated H9c2 cells with an autophagy inhibitor Bafilomycin A1 (Baf A1, 50 nM, 2 h). It has been previously documented that High-mobility group box 1 (HMGB1) was involved in DIC. In our work, knockdown of HMGB1 significantly increased cell viability and LC3 II level in H9c2, suggesting HMGB1 was crucial in DOX-induced autophagy-triggering cell death. Intriguingly, GL is a direct inhibitor of HMGB1. We found that GL downregulated Akt/mTOR autophagy signaling pathway in DOX-treated H9c2 cells. More importantly, in non-silencing H9c2 cells (transfected with negative control siRNA) cells, the expression of phospho-Akt, phospho-mTOR, p62, and LC3 II was significantly decreased with GL pretreament compared to DOX alone. However, in H9c2/HMGB1 － (transfected with HMGB1 siRNA) cells exposed to DOX, the expression of p-Akt, p-mTOR, p62, LC3 II had no statistical difference with or without GL, revealing that HMGB1 mediated the cardioprotective action of GL in DIC. Taken together, our findings demonstrate that improved autophagy flux via HMGB1-dependent Akt/mTOR signaling pathway might contribute to attenuate DIC and go a novel insight into the underlying mechanisms of GL’s cardioprotective action. GL could be a potential candidate for the prevention of DIC.
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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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2022
·
IF 4.601
Jingtong Xia,Minhua Qian,Jiahao Zhou,Zhaoyan Wang,Hongli Li,Lei Zhou,Qiaosheng Pu
ABSTRACT Salvianolic acids (SAs) are a class of natural active substances that have been widely used in clinical treatment and food adjuvant therapy. In this work, we found that SAs could form the ternary complex with borax and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD), thereby sensitizing their weak intrinsic fluorescence to maximized 92-fold for salvianolic acid B (SAB). The formation of ternary complex was dynamic and could complete once mixed, and the fluorescence intensity remained stable within 3 h. On this basis, an integrated strategy of derivatization and separation was proposed for the sensitive analysis of SAs using capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection. After the systematic investigation, a solution consisting of 20 mM borax and 20 mM HP-β-CD (pH 8.5) was selected as the running buffer. By the direct injection of SAs, the dynamic derivatization was realized in the capillary, and the baseline separation was achieved within 6 min, with the detection limits of 1.2-21.2 nM for four SAs (S/N=3). Then, the developed CE-LIF method was successfully applied to the quantitative analysis of SAs in four traditional ginsengs, including Salvia miltiorrhiza, Codonopsis pilosula, Panax quinquefolius and Panax ginseng with the recoveries ranging from 95.2% to 110.7%. Except for four target SAs, a large number of unknown electrophoretic peaks had also been observed in four ginsengs, and then were utilized for the identification of ginseng species via principal component analysis. Furthermore, a hypoxia/reoxygenation model was constructed using Rat cardiomyocyte H9c2 cells, and subsequently, the developed method was applied to continuously monitor the consumption of SAB in cell culture medium after its intervention.
研究领域:
分析化学
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药学
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生物医学工程
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植物化学
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产品关联
DOI
PubMed
高影响因子
Chinese Herbal Medicines
·
2024
·
IF 4.7
Cuiping Long,Qian Zhou,Min Xu,Xin Ding,Xingxing Zhang,Ya Zhang,Yuping Tang,Guangguo Tan
Objective Myocardial inflammation during myocardial infarction (MI) could be inhibited by regulating arachidonic acid (AA) metabolism. Recent studies demonstrated that Sini Decoction (SND) was identified to be an effective prescription for treating heart failure (HF) caused by MI. But the anti-inflammatory mechanism of SND remained unclear. The work was designed to investigate the anti-inflammatory mechanism of SND through the AA metabolism pathway in vitro and in vivo experiments. Methods An inflammatory injury model of H9c2 cells was established by lipopolysaccharide (LPS)-stimulated macrophage-conditioned media (CM). The animal MI model was built by the ligation of left anterior descending (LAD) branch of coronary artery in rat. Meanwhile, the rats were divided into five groups: sham group, MI group, MI + Celecoxib group, MI + low-dose SND group (SND-L) and MI + high-dose SND group (SND-H). Cardiac function, histopathological changes and serum cytokines were examined four weeks later. Western blot analysis was conducted to verify the key enzymes levels in the AA metabolic pathway, including phospholipase A2 (PLA2), cyclooxygenases (COXs) and lipoxygenases (LOXs). Results These in vivo results demonstrated that SND could improve the cardiac function and pathological changes of rats with MI, and regulate the key inflammatory molecules in the AA metabolism pathway, including sPLA2, COX-1, COX-2, 5-LOX and 15-LOX. In vitro , SND could decrease the release of pro-inflammatory cytokines including TNF-α and IL-6 and inhibit cell apoptosis in CM-induced H9c2 cells. Moreover, SND could protect H9c2 cells from the damage of CM by regulating nuclear factor kappa-B (NF-κB) signal pathway and the expression of COX-2. Conclusion SND may be a drug candidate for anti-inflammatory treatment during MI by regulating the multiple targets in the AA metabolism pathway.
研究领域:
药理学
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心脏病学
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分子生物学
·
炎症研究
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产品关联
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2012
·
IF 4.774
Yuan-yuan Chai,Fang Wang,Yan-li Li,Ke Liu,Hui Xu
Rheum emodi Wall has been reported to possess protective effect in many inflammatory diseases and oxidative stress-related injuries. This study aims to investigate antioxidant power of stilbenoids from R. emodi and then explore the material basis for its antioxidant potential. The most abundant stilbenoid piceatannol-4′-O-β-D-glucopyranoside (PICG) and its aglycon piceatannol (PICE) were isolated from R. emodi rhizome. Using well-accepted antioxidant chemicals as reference, antioxidant activity of these stilbenoids was examined by measuring DPPH and superoxide anion radical scavenging, ferric reducing power, and inhibition of lipid peroxidation in vitro. Both PICG and PICE displayed promising antioxidant activity in all the four assays. Comparisons among the tested compounds indicated that PICE has the most potent antioxidant activity and the presence of 3′-hydroxyl group may enhance antioxidant activity of stilbenoids. The antioxidative effect of PICE at the cellular level was further demonstrated on the model of hydrogen-peroxide-induced H9c2 rat cardiomyoblasts injury. Taking into account the rapid in vivo metabolic transformation of PICG into PICE it can be inferred that the most abundant stilbenoid PICG may be an important constituent responsible for the antioxidant potential of R. emodi and promising to be developed as an antioxidant agent for supplementary or therapeutic use.
研究领域:
药理学
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生物化学
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药物化学
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产品关联
DOI
PubMed
高影响因子
Immunity Inflammation and Disease
·
2024
·Vol. 12
·期 5
·e1229
·
IF 3.1
Meng Zhang,Deyuan Zhi,Pei Liu,Yajun Wang,Meili Duan
Background Dioscin has many pharmacological effects; however, its role in sepsis-induced cardiomyopathy (SIC) is unknown. Accordingly, we concentrate on elucidating the mechanism of Dioscin in SIC rat model. Methods The SIC rat and H9c2 cell models were established by lipopolysaccharide (LPS) induction. The heart rate (HR), left ventricle ejection fraction (LVEF), mean arterial blood pressure (MAP), and heart weight index (HWI) of rats were evaluated. The myocardial tissue was observed by hematoxylin and eosin staining. 4-Hydroxy-2-nonenal (4-HNE) level in myocardial tissue was detected by immunohistochemistry. Superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities in serum samples of rats and H9c2 cells were determined by colorimetric assay. Bax, B-cell lymphoma-2 (Bcl-2), toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), phosphorylated-p65 (p-p65), and p65 levels in myocardial tissues of rats and treated H9c2 cells were measured by quantitative real-time PCR and Western blot. Viability and reactive oxygen species (ROS) accumulation of treated H9c2 cells were assayed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and dihydroethidium staining assays. Results Dioscin decreased HR and HWI, increased LVEF and MAP, alleviated the myocardial tissue damage, and reduced 4-HNE level in SIC rats. Dioscin reversed LPS-induced reduction on SOD, CAT, GSH, and Bcl-2 levels, and increment on Bax and TLR4 levels in rats and H9c2 cells. Overexpressed TLR4 attenuated the effects of Dioscin on promoting viability, as well as dwindling TLR4, ROS and MyD88 levels, and p-p65/p65 value in LPS-induced H9c2 cells. Conclusion Protective effects of Dioscin against LPS-induced SIC are achieved via regulation of TLR4/MyD88/p65 signal pathway.
研究领域:
药理学
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心脏病学
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免疫学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEMBRANE SCIENCE
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2022
·
IF 10.53
Qi Chen,Miaoshen Kou,Yang He,Yiping Zhao,Li Chen
Chronic kidney disease (CKD) patients undergoing hemodialysis is often accompanied by high levels of oxidative stress, profoundly affecting the survival rate and long-term outcome of patients. Functionalized hemodialysis membranes with relieving oxidative stress and outstanding biocompatibility have aroused more attention among researchers. In this work, we incorporated a tannic acid (TA) coating onto the poly (ether sulfone) (PES) hemodialysis membrane in order to alleviate the increased oxidative stress status during hemodialysis. Further modification of poly(2-ethyl-2-oxazoline) (PEtOx) brushes devoted to improving the biocompatibility of hemodialysis membrane. The TA/PEtOx brushes functionalized membranes effectively eliminated reactive oxygen species (ROS), increased serum antioxidant level, and inhibited lipid peroxides and glycation products generation. The functionalized membranes attenuated the H 2 O 2 -induced oxidative damage to cardiomyocytes (H9C2) and vascular endothelial cells (HUVEC) by modulating the antioxidant enzymes expression (SOD, CAT and GSH). The immobilization of PEtOx brushes significantly improved the biocompatibility, and the TA/PEtOx brushes functionalized membranes have been constructed through the Michael addition reaction between TA and PEtOx brushes. Simultaneously, the cyclic PEtOx (C-PEtOx) brushes simulating the structure of endothelial glycocalyx formed a stronger steric hindrance and a denser hydration layer that significantly suppressed the platelets and erythrocytes adhesion on membrane surface. The optimal functionalized membrane exhibited a 76.5% of urea clearance, 53.4% of lysozyme clearance and 95.9% of bovine serum albumin (BSA) retention. This present work fabricated a biomimetic surface structure for the development and preparation of novel hemodialysis membrane, which would greatly improve the therapeutic effect in patients.
研究领域:
生物医学工程
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材料科学
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生物材料
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细胞生物学
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肾病学
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Shasha Zhu,Wei Zhang,Chunming Xu,Jie Huang,Cao Zou
Myocardial ischemia-reperfusion injury (MIRI) significantly contributes to the high incidence of complications and mortality associated with acute myocardial infarction. Recently, injectable electroconductive hydrogels (IECHs) have emerged as promising tools for replicating the mechanical, electroconductive, and physiological characteristics of cardiac tissue. Herein, we aimed to develop a novel IECH by incorporating irbesartan as a drug delivery system (DDS) for cardiac repair. Our approach involved merging a conductive poly-thiophene derivative (PEDOT: PSS) with an injectable dual-network adhesive hydrogel (DNAH) comprising a catechol-branched polyacrylamide network and a chitosan-hyaluronic acid covalent network. The resulting P-DNAH hydrogel, benefitting from a high conducting polymer content, a chemically crosslinked network, a robust dissipative matrix, and dynamic oxidation of catechol to quinone exhibited superior mechanical strength, desirable conductivity, and robust wet-adhesiveness. In vitro experiments with the P-DNAH hydrogel carrying irbesartan (P-DNAH-I) demonstrated excellent biocompatibility by cck-8 kit on H9C2 cells and a rapid initial release of irbesartan. Upon injection into the infarcted hearts of MIRI mouse models, the P-DNAH-I hydrogel effectively inhibited the inflammatory response and reduced the infarct size. In conclusion, our results suggest that the P-DNAH hydrogel, possessing suitable mechanical properties and electroconductivity, serves as an ideal IECH for DDS, delivering irbesartan to promote heart repair.
研究领域:
生物医学工程
·
心脏病学
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材料科学
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药学
✓ 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）