BIOMEDICINE & PHARMACOTHERAPY
·
2018
·
IF 3.457
Min Chen,Xiaodong Wang,Bo Hu,Jian Zhou,Xin Wang,Wei Wei,Hua Zhou
Echinacoside is a natural ingredient with various pharmacological activities . In this study, we investigated the protective effects of echinacoside on cardiomyocytes (rat H9c2 cells) in an anoxia/reperfusion (A/R) model. Further, the regulatory function of sodium-calcium exchanger protein 3 (SLC8A3/NCX3) as well as the protein kinase B (AKT) signaling were studied. The present results indicated that echinacoside protected against A/R-induced apoptosis in a dose manner, which was characterized by a decrease in the apoptosis and caspase 3 protein levels in H9c2 cells. Further, Ca 2+ uptake were dose-dependently reduced in H9c2 cells by echinacoside under A/R conditions. Whereas, relative mRNA expression of SLC8A3 and protein levels of SLC8A3 and p-AKT showed opposite tendency. On the one hand, the A/R-induced abnormalities in H9c2 cells were remarkably ameliorated by activated p-AKT and over-expression of SLC8A3 but aggravated by inhibited p-AKT, and the aggravated effection were ameliorated by echinacoside. Moreover, protein levels of SLC8A3 were positively regulated by p-AKT signaling. On the other hand, apoptosis and Ca 2+ uptake as well as protein levels of caspase 3 were significantly increased by SLC8A3 silencing in H9c2 cells under normoxic conditions, and this symptom was remarkably reversed by echinacoside or Nimodipine (an antagonis of Ca 2+ ) treatment . Collectively, echinacoside has showed a cardioprotective effect against A/R treatment in a dose dependent manner in vitro, and this cardioprotective effect was potentially achieved via up-regulating p-AKT and SLC8A3.
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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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY IN VITRO
·
2023
·
IF 3.2
Huan Hou,Yaping Yang,Rong Chen,Zhiping Guo
Trastuzumab (TRZ) is a novel targeted anti-tumor agent that significantly improve the survival of patients with human epidermal growth factor receptor (HER2) positive breast cancer. However, its clinical application is limited due to the side effects of cardiotoxicity. Osthole (OST), a coumarin derivative isolated from Cnidium monnieri (L.) Cusson, has previously demonstrated cardioprotective effects. The aim of this study was to observe the protective effect of OST on TRZ-induced cardiomyocytes damage and to explore its potential mechanism. The results showed that OST pretreatment could significantly inhibit TRZ-induced cardiomyocytes damage, markedly increase the ratio of LC3II/I and Beclin-1 protein expression, and reduce the protein expression of p62. OST pretreatment significantly attenuated oxidative stress and apoptosis induced by TRZ, as evidenced by reducing intracellular ROS level, the Bax/Bcl-2 ratio, and Caspase-3 protein expression. Additionally, OST markedly increased the phosphorylation level of p38MAPK and decreased the mTOR phosphorylation level. However, the effects of OST on enhancing autophagy, reducing oxidative stress, apoptosis, and the phosphorylation level of mTOR were reversed after the addition of 3-MA or SB203580. Molecular docking results indicated that OST exerted a good binding ability with the p38MAPK protein. Our findings suggested that OST could protect TRZ-induced cardiomyocytes damage by enhancing autophagy via the p38MAPK/mTOR signaling pathway.
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
ARCHIVES OF TOXICOLOGY
·
2024
·
IF 4.8
Wang Yanwei,Qiu Jingru,Yan Hua,Zhang Nan,Gao Shixuan,Xu Ning,Wang Cuiyan,Lou Haiyan
Doxorubicin (DOX) is one of the most frequently used chemotherapeutic drugs belonging to the class of anthracyclines. However, the cardiotoxic effects of anthracyclines limit their clinical use. Recent studies have suggested that ferroptosis is the main underlying pathogenetic mechanism of DOX-induced cardiomyopathy (DIC). BTB-and-CNC homology 1 (Bach1) acts as a key role in the regulation of ferroptosis. However, the mechanistic role of Bach1 in DIC remains unclear. Therefore, this study aimed to investigate the underlying mechanistic role of Bach1 in DOX-induced cardiotoxicity using the DIC mice in vivo (DOX at cumulative dose of 20 mg/kg) and the DOX-treated H9c2 cardiomyocytes in vitro (1 μM). Our results show a marked upregulation in the expression of Bach1 in the cardiac tissues of the DOX-treated mice and the DOX-treated cardiomyocytes. However, Bach1 −/− mice exhibited reduced lipid peroxidation and less severe cardiomyopathy after DOX treatment. Bach1 knockdown protected against DOX-induced ferroptosis in both in vivo and in vitro models. Ferrostatin-1 (Fer-1), a potent inhibitor of ferroptosis, significantly alleviated DOX-induced cardiac damage. However, the cardioprotective effects of Bach1 knockdown were reversed by pre-treatment with Zinc Protoporphyrin (ZnPP), a selective inhibitor of heme oxygenase-1(HO-1). Taken together, these findings demonstrated that Bach1 promoted oxidative stress and ferroptosis through suppressing the expression of HO-1. Therefore, Bach1 may present as a promising new therapeutic target for the prevention and early intervention of DOX-induced cardiotoxicity.
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
JOURNAL OF FOOD SCIENCE
·
2020
·Vol. 85
·期 6
·1752-1763
·
IF 2.479
Shilian Zheng,Zeyuan Deng,Fang Chen,Liufeng Zheng,Yao Pan,Qian Xing,Rong Tsao,Hongyan Li
Phenolics and carotenoids coexist in fruits and vegetables and could possess interaction effects after consumption. The present study aims to elucidate the possible mechanisms of the antioxidant interactions between anthocyanins and carotenoids using petunidin and lycopene as examples in hydrogen peroxide (H 2 O 2 )-induced heart myofibroblast cell (H9c2) line model. The results revealed that petunidin and lycopene showed antioxidant effects and petunidin in a larger proportion mixed with lycopene, for example, petunidin: lycopene = 9:1 significantly protected against the loss of the cell viability (8.98 ± 1.03%) and intracellular antioxidant enzyme activities of superoxide dismutase (SOD, 27.07 ± 3.51%), catalase (CAT, 29.51 ± 6.12%), and glutathione peroxidase (GSH-Px, 20.33 ± 2.65%). Moreover, the messenger RNA (mRNA) and protein expressions of NAD(P)H quinone reductase (NQO1) and heme oxygenase (HO-1) of the nuclear factor erythrocyte 2-related factor 2 (Nrf2) signaling pathway were significantly induced in petunidin, lycopene, and synergistic combinations, suggesting that the antioxidant action was through activating the Nrf2 antioxidant response pathway. This was further validated by Nrf2 siRNA, and the results that petunidin significantly induced more of NQO1 expression and lycopene more of HO-1 suggested that the synergism may be a result of concerted actions by the two compounds on these two different target genes of the Nrf2 pathway. The two compounds also significantly increased the phosphorylation of Akt in synergistic combinations. Findings of the present study demonstrated that petunidin and lycopene exerted synergistic antioxidant effects when petunidin in a larger proportion in the combinations and contribute to the prevention of cellular redox homeostasis, which might provide a theoretical basis for phenolics and carotenoids playing beneficial effects on the cardiovascular risk. Practical Application In this study, we revealed that the combined treatments of petunidin and lycopen inhibited H 2 O 2 -induced oxidative damage in myocardial cells. Moreover, the treatments contributed to the Nrf2 pathway and the restoration of cellular redox homeostasis might provide a theoretical basis for phenolics and carotenoids playing beneficial effects on the cardiovascular risk.
研究领域:
药理学
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细胞生物学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2021
·Vol. 16
·期 1
·1-16
·
IF 4.703
Zhou Lin,Huang Zhi,Yang Shanyi,Wei Jiarui,Xu Yan,Hu Lin,Guo Xinrong,Yuan Limin,Yuan Zexuan,Yang Xiaoping,Tao Xiaojun,Zhang Qiufang
Hydrophilic polyethylene glycol monomethyl ether (mPEG) was grafted onto Icariin (ICA) by succinic anhydride to form a polyethylene glycol-Icariin (mPEG-ICA) polymer. The structure of the polymer was characterized by Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). mPEG-ICA nanoparticles loaded with ICA were prepared by physical embedding of ICA by dialysis. The particle size was determined to be (220 ± 13.7) nm, and the ζ potential was (2.30 ± 1.33) mV by dynamic light scattering (DLS). Under a transmission electron microscope (TEM), the nanoparticles were spherical, and the morphology was regular. In the medium with pH 7.4, the drug release rate of mPEG-ICA nanoparticles reached (52.80 ± 1.70)% within 72 h. At pH 6.8, the cumulative drug release of nanoparticles reached (75.66 ± 0.17)% within 48 h. Treatment of the nanoparticles with LPS-treated H9c2 cells maintained cell viability, reduced LDH release and exerted antiapoptotic effects. Moreover, ICA-loaded mPEG-ICA nanoparticles significantly decreased the mRNA expression of the myocardial inflammatory cytokines TNF-α, IL-1β and IL-6M. In conclusion, ICA-loaded mPEG-ICA nanoparticles protected against LPS-induced H9c2 cell injury.
研究领域:
药学
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纳米技术
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细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2022
·
IF 5.307
Chunmei Bai,Qianqian Ma,Qi Li,Lijun Yu,Dong Zhen,Mingjie Liu,Chengxi Wei
Combination drug therapy has become an effective strategy for chronic metabolic disease, especially cardiovascular disease. In the present study, possible drug combinations were screened and the mechanism of the combinations against cardiac hypertrophy was examined within 1,8-cineole, β -caryophyllene, linalool, and β -pinene.H9c2 cells were treatment with 1,8-cineole, β -caryophyllene, linalool, and β -pinene individually or in combination for 24 h after isoprenaline stimulation. Cell viability was detected by the MTT assay. Subsequently, bioinformatic analysis and network pharmacology were used to reveal the multi-targeted synergistic therapeutic effect of the combination treatment compounds on cardiac hypertrophy. Ultimately, western blot and elisa was performed to analyses the protein expression in vivo . MTT results found that 1,8-cineole and β -caryophyllene synergistically increased cell viability with CalcuSyn software analyses. Specifically, bioinformatic and network pharmacology analysis showed PTGS2, TNF, IL-6, AKT1, NOS2, and CAT were identified as the key targets. P13K-AKT signaling pathway was involved in the reversal of cardiac hypertrophy by the combination of 1,8-cineole and β -caryophyllene. The in vitro results indicated that the combination synergistically treated the isoprenaline-induced mice against structural and functional myocardial damage via the P13K-AKT signaling pathway. Collectively, the combined application of 1,8-cineole and β -caryophyllene synergistically reverses cardiac hypertrophy in isoprenaline-induced H9c2 cells and mice.
研究领域:
药理学
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心血管疾病
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细胞生物学
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网络药理学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2021
·Vol. 476
·期 6
·2479-2489
·
IF 3.396
Chai Qian,Meng Ziang,Lu Dexue,Zhang Ziying,Liu Meili,Wu Weihua
Cardiomyocyte death is an important pathogenic process in cardiac complications of diabetes. Diabetic patients often suffer glycemic variability. Pyroptosis is a form of programmed cell death triggered by inflammasomes and related with caspase-1 and gasdermin D activation. The present study was designed to examine the effects of intermittent high glucose simulating glycemic variability on the pyroptosis of cardiomyocytes in vitro. Rat H9C2 cardiomyocytes were incubated with normal glucose (NG), constant high glucose (CHG) and intermittent high glucose (IHG). Results showed that compared to CHG treatment, IHG further inhibited cell proliferation and promoted cell death of H9C2 cardiomyocytes. In addition, IHG upregulated higher levels of the expressions of inflammasome NLR family pyrin domain containing 3 (NLRP3) and adaptor protein apoptosis-associated speck-like protein containing CARD domain (ASC) and increased higher levels of activated caspase-1 and gasdermin D than CHG treatment. Moreover, the production of reactive oxygen species (ROS) and activation of NF-κB that is induced by IHG were significantly higher than that induced by CHG. Knockdown of sodium–glucose cotransporters 1 (SGLT1) in H9C2 cardiomyocytes was performed and the effects of SGLT1 on IHG-induced pyroptosis was evaluated. The results demonstrated that knockdown of SGLT1 partially reduced IHG-induced pyroptosis, ROS generation and NF-κB activation. Our results indicated that IHG is harmful to cardiomyocytes and it might be partially because of the SGLT1-depedent pyroptosis in cardiomyocytes.
研究领域:
心脏病学
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糖尿病
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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
FOOD CHEMISTRY
·
2020
·
IF 6.306
Yao Pan,Ze-Yuan Deng,Xuan Chen,Bing Zhang,Yawei Fan,Hongyan Li
Phenolic acids (caffeic acid, p -coumaric acid,) and carotenes (β-carotene, lycopene) were mixed in different ratios to investigate antioxidant interactions on H 2 O 2 -induced H9c2 cells with ezetimibe (inhibitor of carotenes membrane transporters). Cellular uptake of carotenes, expression of membrane transporters, reactive oxygen species (ROS), nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H dehydrogenase quinone1 (NQO1), heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) were analyzed. Results revealed that phenolic acids increased cellular uptake of carotenes and expression of their membrane transporters. Combination groups contained more phenolic acids showed synergistic effects. For example, β-carotene: caffeic acid = 1:2 significantly suppressed the intracellular ROS (+EZT, 66.34 ± 51.53%) and enhanced the accumulation of nucleus-Nrf2 (+EZT, 30.23 ± 5.30) compared to the groups contained more β-carotene (+EZT, ROS: 75.48 ± 2.55%, nucleus-Nrf2: 19.48 ± 4.22). This study provided an implication of functional foods formulation and demonstrated that antioxidant synergism may due to the up-regulation of carotenes membrane transporters by phenolic acids.
研究领域:
药理学
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细胞生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
NUTRITION RESEARCH
·
2019
·
IF 2.627
Jia Wang,Tian Gao,Feng Wang,Jie Xue,Hua Ye,Meilin Xie
Luteolin , a natural flavonoid , can attenuate hepatic lipid accumulation and insulin resistance in obese mice . Therefore, we hypothesized that luteolin may also improve the abnormal glucolipid metabolism of hypertrophic myocardial cells. This study aimed to investigate the effect and possible molecular mechanisms of luteolin. Hypertrophic H9c2 cells were induced by angiotensin II/hypoxia and simultaneously treated with 2 to 8 μg/mL luteolin for 24 h. Luteolin might dose-dependently decrease intracellular total protein, atrial natriuretic peptide , and free fatty acid levels , and increase supernatant glucose levels . Western blot assay showed that luteolin could inhibit the expressions of intracellular hypoxia inducible factor-1α (HIF-1α) and glucose transporter-4 (GLUT-4) proteins, and increase the expressions of intracellular peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase-1A (CPT-1A), and pyruvate dehydrogenase kinase-4 (PDK-4) proteins. These findings demonstrate that luteolin can improve abnormal glucolipid metabolism in angiotensin II/hypoxia-induced hypertrophic H9c2 cells, and its mechanisms are related to the inhibition of HIF-1α expression and subsequent modulation of PPARα-mediated target genes, including CPT-1A, PDK-4, and GLUT-4.
研究领域:
药理学
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心脏病学
·
细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE
·
2015
·Vol. 36
·期 3
·873-880
·
IF 2.088
Yu Lou,Zhen Wang,Yi Xu,Ping Zhou,Junxian Cao,Yuanshi Li,Yeping Chen,Junfeng Sun,Lu Fu
Treatment with doxorubicin (DOX) is one of the major causes of chemotherapy-induced cardiotoxicity and is therefore, the principal limiting factor in the effectiveness of chemotherapy for cancer patients. DOX‑induced heart failure is thought to result from endoplasmic reticulum (ER) stress and cardiomyocyte apoptosis. Resveratrol (RV), a polyphenol antioxidant found in red wine, has been shown to play a cardioprotective role. The aim of the present study was to examine the effects of RV on DOX‑induced cardiotoxicity in H9c2 cells. We hypothesized that RV would protect H9c2 cells against DOX‑induced ER stress and subsequent cell death through the activation of the Sirt1 pathway. Our results demonstrated that the decrease observed in the viability of the H9c2 cells following exposure to DOX was accompanied by a significant increase in the expression of the ER stress‑related proteins, glucose‑regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). However, we found that RV downregulated the expression of ER stress marker protein in the presence of DOX and restored the viability of the H9c2 cells. Exposure to RV or DOX alone only slightly increased the protein expression of Sirt1, whereas a significant increase in Sirt1 protein levels was observed in the cells treated with both RV and DOX. The Sirt1 inhibitor, nicotinamide (NIC), partially neutralized the effects of RV on the expression of Sirt1 in the DOX‑treated cells and completely abolished the effects of RV on the expression of GRP78 and CHOP. The findings of our study suggest that RV protects H9c2 cells against DOX‑induced ER stress through ER stabilization, and more specifically through the activation of the Sirt1 pathway, thereby leading to cardiac cell survival.
研究领域:
药理学
·
心脏病学
·
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
Frontiers in Pharmacology
·
2023
·
IF 5.6
Zhang Xiuying,Chen Qilei,Zhao Jia,Zhao Wei,Fan Ni,Wang Yu,Chen Hubiao,Rong Jianhui
Myocardial infarction (MI) is a highly prevalent and lethal disease worldwide. Prevention and timely recovery are critical for the control of the recurrence and heart failure in MI survivors. The present study was designed to investigate the cardioprotective activity of the herbal medicine formula Baoyuan Decoction (BYD) and identify the active compounds and molecular targets. The ethanolic BYD extract (BYDE) was prepared by water extraction and ethanol precipitation of four herbal medicines, Astragali Radix, Ginseng Radix et Rhizoma, Cinnamomi Cortex, and Glycyrrhizae Radix et Rhizoma. Initially, BYDE was validated for the cardioprotective effectiveness in a mouse model of ischemia injury and rat cardiomyocyte H9C2 cells. As results, BYDE effectively reduced infarct size from 56% to 37% and preserved cardiac functions in mouse MI model while protected H9C2 cells against oxygen glucose deprivation. Subsequent network pharmacology analysis revealed that 122 bioactive ingredients, including flavonoids and saponins from the UPLC-MS/MS profile of BYDE, might target 37 MI-related proteins, including inflammatory and apoptotic mediators (e.g., TNF, NFKB1, CASPs, TNFRSF1A, CXCL12, BCL2A1). Pathway enrichment analysis suggested that BYDE might control the cardiac inflammation via targeting the tumor necrosis factor-alpha (TNF-α)/nuclear factor-κB (NF-κB) pathway while the selected targets were also implicated in IL-17 signaling pathway, lipid and atherosclerosis. Consequently, adenosine, ginsenoside Rh2, isoliquiritigenin, and licochalcone A were selected to generate the four-compound mixture AGILe and validated for the inhibitory effects on the TNF-α/NF-κB pathway. The results of the present study suggested that the mixture AGILe might be a potential cardioprotective remedy against MI.
研究领域:
药理学
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心脏病学
·
中医药
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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
ANNALS OF CLINICAL AND LABORATORY SCIENCE
·
2025
·Vol. 55
·期 6
·939-953
·
IF 1
Yu Zhang,Guangju Zhou
Objective Ectoine is a natural compatible solute known for its cytoprotective properties, though its potential role in alleviatingdiabetic cardiomyopathy remains largely unexplored. This study aimed to examine the protective effects and underlying mechanismsof Ectoine on H9c2 cardiomyocytes under high-glucose and high-palmitic acid conditions. Methods The investigation included assessment of cell viability and lactate dehydrogenase release. Oxidative stress was evaluatedthrough measurements of reactive oxygen species, malondialdehyde levels, and superoxide dismutase activity. Inflammatory responseswere analyzed via TNF-α secretion and NF-κB and ERK1/2 pathways. Molecular docking studies were conducted to explore Ectoine-AMPK interaction, while mechanistic insightswere gained through examination of AMPK signaling, energy metabolism regulators, autophagic flux markers, and mitochondrialapoptosis. Results Ectoine treatment was associated with enhanced cell viability and reduced lactate dehydrogenase release. It appeared to alleviateoxidative stress through decreased reactive oxygen species and malondialdehyde levels, along with increased superoxide dismutaseactivity. Ectoine also showed suppressive effects on inflammatory responses, including reduced TNF-α secretion and inhibited NF-κB and ERK1/2 pathways. Molecular docking suggested binding affinity between Ectoine and AMPK (−6.4 kcal/mol). Mechanistically,Ectoine demonstrated potential in activating AMPK signaling, modulating energy metabolism, restoring autophagic flux, andattenuating mitochondrial apoptosis. Conclusion The findings suggest that Ectoine may protect against HG-PA-induced cardiomyocyte injury. This protective effect was associatedwith AMPK activation and the coordinated modulation of metabolic, autophagic, anti-inflammatory, and anti-apoptotic pathways.This study suggests the therapeutic potential of Ectoine and provides a basis for further investigation.
研究领域:
心血管研究
·
分子生物学
·
细胞生物学
·
代谢性疾病
·
药理学
✓ 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）