Modulations of Keap1-Nrf2 signaling axis by TIIA ameliorated the oxidative stress-induced myocardial apoptosis

Yan, Shihai; Zhao, Ningwei; Geng, Zhirong; Shen, Jiayin; Liu, Fuming; Dong, Yan; Zhou, Jie; Nie, Chao; Huang, Chengcai; Fang, Zheng

doi:10.1016/j.freeradbiomed.2017.12.001

Cited by 45 publications

(26 citation statements)

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“…The ratio of Bcl-2 to Bax is critical in determining cell apoptosis and survival. Most importantly, the activation of caspase-3 is considered as an initiating factor for myocardial cells apoptosis [39]. CoCl 2 could induce a significant decline of the Bcl-2/Bax ratio followed by activation of caspase-3 cleavage.…”

Section: Discussionmentioning

confidence: 99%

Genistein Protects H9c2 Cardiomyocytes against Chemical Hypoxia-Induced Injury via Inhibition of Apoptosis

Shi¹,

Zhang²,

Hu³

et al. 2019

Pharmacology

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Background/Aims: Hypoxia can induce cell injury in cardiomyocytes and further lead to cardiovascular diseases. Genistein (Gen), the predominant isoflavone found in soy products, has shown protective effects on cardiovascular system. The aim of the present study was to investigate the cardioprotective effect of Gen against chemical hypoxia-induced injury. Methods: Cobalt chloride (CoCl₂) was administrated to trigger chemical hypoxia in H9c2 cardiomyocytes. Cell proliferation was detected by using MTT assay. The expression level of hypoxia-related proteins (hypoxia-inducible factor [HIF]-1α and Notch-1) and apoptosis-related proteins (B cell lymphoma [Bcl]-2, Bax, and caspase-3) were evaluated by Western blot analysis. Results: In response to hypoxia, cell viability was reduced dramatically, whereas the expression of HIF-1α was upregulated. Hypoxia also induced cardiomyocytes apoptosis by reducing the ratio of Bcl-2/Bax and increasing expression of caspase-3. Interestingly, Gen attenuated CoCl₂-induced cell death and suppressed HIF-1α expression, as well as upregulated the expression of Notch-1. Furthermore, Gen could antagonize CoCl₂-induced apoptosis through upregulating Bcl-2/Bax ratio and inhibiting caspase-3 expression. Conclusions: Gen prevents chemical hypoxia-induced cell apoptosis through inhibition of the mitochondrial apoptotic pathway, exerting protective effects on H9c2 cardiomyocytes.

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Section: Discussionmentioning

confidence: 99%

Genistein Protects H9c2 Cardiomyocytes against Chemical Hypoxia-Induced Injury via Inhibition of Apoptosis

Shi¹,

Zhang²,

Hu³

et al. 2019

Pharmacology

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“…Thus, other treatments that synergize with RAAS inhibitors to further interfere with events leading to interstitial inflammation and structural damage are desirable (Remuzzi and Bertani, 1998). Danshen, a popular Chinese herb from dried roots of S. miltiorrhiza Bunge, has been used for over 2,000 years for the treatment of cardiovascular diseases without obvious side effects (Yan et al, 2018). Tanshinone IIA, one of the major constituents extracted from Danshen, is officially regarded as a quality control marker as per Chinese Pharmacopoeia (Yan et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

“…Danshen, a popular Chinese herb from dried roots of S. miltiorrhiza Bunge, has been used for over 2,000 years for the treatment of cardiovascular diseases without obvious side effects (Yan et al, 2018). Tanshinone IIA, one of the major constituents extracted from Danshen, is officially regarded as a quality control marker as per Chinese Pharmacopoeia (Yan et al, 2018). Sodium tanshinone IIA sulfonate injection is a water-soluble derivative of tanshinone IIA and has become commercially available in China.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Sodium Tanshinone IIA Sulfonate Injection on Hypertensive Nephropathy: A Systematic Review and Meta-Analysis

Zhang

Shi

et al. 2019

Front. Pharmacol.

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Background: Sodium tanshinone IIA sulfonate (STS) injection, the extractive of traditional Chinese medicine Danshen, is supposed to be a supplementary treatment in hypertensive nephropathy. Objectives: To evaluate the efficacy and safety of STS in treatment of hypertensive nephropathy. Methods: We systematically searched China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan-fang database, Chinese Biomedicine Database (CBM), PubMed, Embase, Web of Science, and Cochrane Library from their inception to December 2018. All studies were screened by two reviewers according to the inclusion and exclusion criteria independently. The Cochrane Collaboration's risk tool was used to assess the methodological quality of the included studies. Reviewer Manager 5.3 was employed for statistical analysis. Results: Sixteen trials involving 1,696 patients were included. The meta-analysis results indicated a combination of STS and angiotensin receptor blockers (ARBs) was more effective than ARB monotherapy in modulating hypertensive nephropathy, as represented by improved estimated glomerular filtration rate (eGFR) [mean difference (MD) = 6.87, 95% CI (4.47, 9.28), P < 0.00001] and reduced 24 h urinary protein [MD = −0.23, 95% CI (−0.27, −0.19), P < 0.00001], serum creatinine (SCr) [MD = −21.74, 95% CI (−24.11, −19.38), P < 0.00001], cystatin-C [MD = −0.16, 95% CI (−0.24, −0.07), P = 0.0003], urinary immunoglobulin G (IgG) [MD = −0.85, 95% CI (−1.11, −0.59), P < 0.00001], and urinary transferrin [MD = −0.61, 95% CI (−1.04, −0.17), P = 0.007]. In addition, the combination therapy had better control in systolic blood pressure (SBP) [MD = −6.53, 95% CI (−8.19, −4.87), P < 0.00001] and diastolic blood pressure (DBP) [MD = −4.14, 95% CI (−5.69, −2.59), P < 0.00001]. Only three trials reported adverse events, and no adverse drug reactions were observed.

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“…The results demonstrated that high oxidative stress levels were observed in the IH exposed tumor-bearing mice, and TSA can attenuate these levels, especially under the IH condition. This phenomenon may partly attribute to Nrf2, one of the antioxidant genes [32,33].…”

Section: Effect Of Tsa On Nrf2 and Nf-kb Expressionmentioning

confidence: 99%

Sodium tanshinone IIA sulfonate attenuates tumor oxidative stress and enhances apoptosis in an intermittent hypoxia mouse model

Zhang

Chen

et al. 2019

Preprint

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Objective The present study was designed to determine the effect of sodium tanshinone IIA sulfonate (TSA) on tumor oxidative stress and apoptosis in a mouse model of intermittent hypoxia (IH) which was considered a novel feature of obstructive sleep apnea. Materials and methods Mice were randomly assigned to control (normoxia) group (CTL), control plus TSA (CTL+TSA) group, IH group, and IH plus TSA (IH+TSA) group. The IH exposure lasted for 5 weeks. TSA was intraperitoneally injected in the CTL+TSA and IH+TSA group. Malondialdehyde (MDA) and superoxide dismutase (SOD) were detected for tumor oxidative stress levels. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and western blotting of Bax, Cleaved Caspase-3 were conducted for evaluating tumor apoptotic levels. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and NF-κB were also evaluated by western blotting. Results Compared with the CTL group, mice exposed to the IH had higher MDA and lower SOD levels, and the TUNEL-positive cell rate, Bax and Cleaved Caspase-3 expressive levels were decreased in the IH group. The oxidative stress indexes were suppressed and the apoptotic levels were upregulated after treatment with TSA under the IH condition. The lower Nrf2 and higher NF-κB levels can be reversed by tretment with TSA under the IH condition. Conclusions The IH contributes to high oxidative stress and low apoptosis in tumor-bearing mice. TSA appears to improve IH-induced oxidative stress and apoptosis via Nrf2/NF-κB signaling pathway.

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Modulations of Keap1-Nrf2 signaling axis by TIIA ameliorated the oxidative stress-induced myocardial apoptosis

Cited by 45 publications

References 50 publications

Genistein Protects H9c2 Cardiomyocytes against Chemical Hypoxia-Induced Injury via Inhibition of Apoptosis

Genistein Protects H9c2 Cardiomyocytes against Chemical Hypoxia-Induced Injury via Inhibition of Apoptosis

Efficacy and Safety of Sodium Tanshinone IIA Sulfonate Injection on Hypertensive Nephropathy: A Systematic Review and Meta-Analysis

Sodium tanshinone IIA sulfonate attenuates tumor oxidative stress and enhances apoptosis in an intermittent hypoxia mouse model

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