Clematichinenoside (AR) Attenuates Hypoxia/Reoxygenation-Induced H9c2 Cardiomyocyte Apoptosis via a Mitochondria-Mediated Signaling Pathway

Ding, Haiying; Rong, Han; Chen, Xueshan; Fang, Weirong; Li, Meng; Wang, Xuemei; Wei, Qin; Kodithuwakku, Nandani Darshika; Li, Yunman

doi:10.3390/molecules21060683

Cited by 14 publications

(9 citation statements)

References 35 publications

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“…Bcl-2 and Bax are the major members of the Bcl-2 protein family, which are involved in mitochondrion-mediated apoptosis. The former demonstrates an anti-apoptotic effect, whereas the latter exhibits a pro-apoptotic effect (29). In the present study, the expression of Bcl-2 was downregulated by hypoxia/reoxygenation in contrast to that in the control group.…”

Section: Effect Of Eriodictyol On Caspase-3 Activity and Expression Lcontrasting

confidence: 54%

Eriodictyol protects H9c2 cardiomyocytes against the injury induced by hypoxia/reoxygenation by improving the dysfunction of mitochondria

Xie

Han³

2018

Exp Ther Med

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Myocardial infarction is a leading cause of mortality worldwide, while myocardial ischemia and timely reperfusion contribute to myocardial injury. The mitochondria are involved in the injury and mediate the apoptosis of cardiomyocytes. In order to develop novel therapeutic approaches for myocardial infarction, the present study evaluated the myocardial protective effects of eriodictyol and investigated relevant mechanisms in H9c2 cardiomyocytes. As a result, eriodictyol was observed to improve the H9c2 cardiomyocyte viability and block the leakage of cytosolic lactate dehydrogenase under hypoxia/reoxygenation. In addition, the dysfunction of mitochondria induced by hypoxia/reoxygenation was ameliorated by eriodictyol through suppressing the overload of intracellular Ca 2+ , preventing overproduction of reactive oxygen species, blocking mitochondrial permeability transition pore opening, increasing mitochondrial membrane potential level and decreasing ATP depletion. Finally, the apoptosis of H9c2 cardiomyocyte induced by hypoxia/reoxygenation was prevented by eriodictyol through upregulation of the expression of B-cell lymphoma-2 (Bcl-2) and downregulation of the expression levels of Bcl-2-associated X protein and caspase-3. These results provided evidence for further investigation on myocardial protection and the treatment of myocardial infarction using eriodictyol.

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Section: Effect Of Eriodictyol On Caspase-3 Activity and Expression Lcontrasting

confidence: 54%

Eriodictyol protects H9c2 cardiomyocytes against the injury induced by hypoxia/reoxygenation by improving the dysfunction of mitochondria

Xie

Han³

2018

Exp Ther Med

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“…Previous findings have suggested that gypenoside protects the cardiomyocytes against the injury via the mitogen-activated protein kinase-mediated nuclear factor-κB pathway (26). In addition, as the convergent pathway of final ischemia and reperfusion injury, mitochondria-mediated apoptosis has been demonstrated to be involved in protective effects of most phytochemicals, including clematichinenoside (27) and ilexsaponin A (28).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of carnosic acid against mitochondria‑mediated injury in H9c2 cardiomyocytes induced by hypoxia/reoxygenation

Liu

Dong

2017

Exp Ther Med

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Abstract. Myocardial ischemia and reperfusion occurs in myocardial infarction. Timely reperfusion will exacerbate the injury through the mitochondria-mediated apoptosis in cardiomyocytes due to the accumulation of excessive reactive oxygen species (ROS). In order to identify novel therapeutic approaches, the cardioprotective effects of carnosic acid and the underlying mechanisms were investigated in the present study in H9c2 cardiomyocytes injured by hypoxia/reoxygenation in vitro. The viability of H9c2 cardiomyocytes was detected by MTT assay and further confirmed by the detection of intracellular lactate dehydrogenase (LDH) release. The mitochondrial function in H9c2 cardiomyocytes was evaluated using fluorescence methods. The proteins related to apoptosis, including caspase-3, B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) were analyzed by western blot analysis, and the activity of caspase-3 was determined using a colorimetric method. As a result, carnosic acid was demonstrated to improve the viability of H9c2 cardiomyocytes and suppress the leakage of cytosolic lactate dehydrogenase under hypoxia/reoxygenation. In addition, the overproduction of intracellular ROS and intracellular calcium overload were ameliorated in the presence of carnosic acid. The dysfunction of mitochondria in H9c2 cardiomyocytes was also attenuated by carnosic acid through blocking the collapse of mitochondrial membrane potential (MMP) and mitochondrial permeability transition pore (mPTP) opening. Furthermore, the apoptosis of H9c2 cardiomyocytes resulted from hypoxia/reoxygenation was inhibited by carnosic acid through the upregulation of Bcl-2 and the downregulation of Bax and caspase-3 levels. These results provided evidence for further investigation that would assist in the development of novel therapeutic approaches for myocardial infarction.

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“…Furthermore, AR has been demonstrated to attenuate I/R injury. Ding et al reported that AR ameliorates myocardial I/R injury in H9c2 cardiomyocytes through the mitochondrial‐mediated apoptotic signalling pathway. However, the effect of AR on renal I/R injury remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Clemaichinenoside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro through activating the Nrf2/HO‐1 signalling pathway

Feng

Kong

Xie

et al. 2019

Clin Exp Pharma Physio

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Renal ischaemia/reperfusion (I/R) is a major cause of acute renal failure with increased morbidity, mortality, and prolonged hospitalizations. Clematichinenoside (AR), a triterpenoid saponin isolated from the roots of Clematis chinensis, was reported to possess a protective effect against I/R injury. However, the effect of AR on renal I/R injury has not been evaluated. This study aims to examine the effect of AR on an in vitro I/R model in human proximal tubular epithelial cells HK‐2. HK‐2 cells were subjected to hypoxia/reoxygenation (H/R) stimulation to mimic I/R in vitro. The results showed that AR improved cell viability of H/R‐stimulated HK‐2 cells. AR pretreatment resulted in decreased production of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as increased in superoxide dismutase (SOD) activity in H/R‐stimulated HK‐2 cells. In addition, AR also presented an anti‐inflammatory activity, as evidenced by decreased secretion of pro‐inflammatory cytokines including IL‐6, IL‐1β, and TNF‐α. Moreover, apoptotic rate was markedly decreased in HK‐2 cells pretreated with AR. The bax expression was decreased, while bcl‐2 expression was increased by AR pretreatment. Furthermore, AR enhanced the H/R‐stimulated activation of the Nrf2/HO‐1 signalling pathway in HK‐2 cells. In conclusion, these findings indicated that AR protected HK‐2 cells from H/R‐induced cell injury via regulating the Nrf2/HO‐1 signalling pathway.

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Clematichinenoside (AR) Attenuates Hypoxia/Reoxygenation-Induced H9c2 Cardiomyocyte Apoptosis via a Mitochondria-Mediated Signaling Pathway

Cited by 14 publications

References 35 publications

Eriodictyol protects H9c2 cardiomyocytes against the injury induced by hypoxia/reoxygenation by improving the dysfunction of mitochondria

Eriodictyol protects H9c2 cardiomyocytes against the injury induced by hypoxia/reoxygenation by improving the dysfunction of mitochondria

Protective effects of carnosic acid against mitochondria‑mediated injury in H9c2 cardiomyocytes induced by hypoxia/reoxygenation

Clemaichinenoside protects renal tubular epithelial cells from hypoxia/reoxygenation injury in vitro through activating the Nrf2/HO‐1 signalling pathway

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