Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes

Huang, Zhouqing; Han, Zhihua; Ye, Bozhi; Dai, Zhenyu; Shan, Peiren; Lu, Zhongqiu; Dai, Kezhi; Wang, Changqian; Huang, Weijian

doi:10.1016/j.ejphar.2015.05.028

Cited by 136 publications

(116 citation statements)

References 47 publications

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“…Autophagy is anti‐apoptotic and contributes to cellular recovery during brief myocardial ischaemia, but the subsequent reperfusion could cause excessive autophagy, which is considered cytotoxic and termed as class II programmed or autophagic cell death 6, 7, 8, 26. Our previous studies showed that inhibiting excessive autophagy could significantly decrease the infarct size and improve cardiac function after I/R‐induced myocardial injury 27, 28. A similar result was observed in vitro in this study.…”

Section: Discussionsupporting

confidence: 87%

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

Huang

Kong

et al. 2016

J Cellular Molecular Medi

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MicroRNAs and autophagy play critical roles in cardiac hypoxia/reoxygenation (H/R)‐induced injury. Here, we investigated the function of miR‐21 in regulating autophagy and identified the potential molecular mechanisms involved. To determine the role of miR‐21 in regulating autophagy, H9c2 cells were divided into the following six groups: control group, H/R group, (miR‐21+ H/R) group, (miR‐21‐negative control + H/R) group, (BEZ235+ H/R) group and (miR‐21+ BEZ235+ H/R) group. The cells underwent hypoxia for 1 hr and reoxygenation for 3 hrs. Cell count kit‐8 was used to evaluate cell function and apoptosis was analysed by Western blotting. Western blotting and transmission electron microscopy were used to investigate autophagy. We found that miR‐21 expression was down‐regulated, and autophagy was remarkably increased in H9c2 cells during H/R injury. Overexpression of miR‐21 with a miR‐21 precursor significantly inhibited autophagic activity and decreased apoptosis, accompanied by the activation of the AKT/mTOR pathway. In addition, treatment with BEZ235, a novel dual Akt/mTOR inhibitor, resulted in a significant increase in autophagy and apoptosis. However, we found that miR‐21‐mediated inhibition of apoptosis and autophagy was partly independent of Akt/mTOR activation, as demonstrated in cells treated with both miR‐21 and BEZ235. We showed that miR‐21 could inhibit H/R‐induced autophagy and apoptosis, which may be at least partially mediated by the Akt/mTOR signalling pathway.

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Section: Discussionsupporting

confidence: 87%

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

Huang

Kong

et al. 2016

J Cellular Molecular Medi

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“…Berberine is an important alkaloid derived from Coptis chinensis Franch (Huang Lian). Previous studies [10][11] indicated that berberine had cardioprotective effects that included lowering lipids, reducing ischemia/reperfusion-induced myocardial apoptosis, and attenuating adverse left ventricular remodeling [12][13][14] . Our previous study in rats with acute myocardial infarction [15] showed that combined ligustrazine and berberine produced more effective inhibition of platelet activation and inflammatory reactions than did either agent separately.…”

Section: Introductionmentioning

confidence: 99%

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

Zhang

Guo

et al. 2016

Acta Pharmacol Sin

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Aim:We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME). Methods: SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses. Results: Pretreatment with the combination of ligustrazine (27 mg·kg -1 ·d -1 ) and berberine (90 mg·kg -1 ·d -1 ) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1β, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg -1 ·d -1 ). Conclusion: The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects.

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“…Also as a bulk cellular degradation pathway, autophagy has been widely reported in its neuroprotective potential [11][12][13] and autophagy is thought to be a protective mechanism that sustain cell survival under stress conditions. By contrast, altercation exist whether excessive autophagy activity contribute to autophagy induced cell death [14][15][16], when autophagy is excessively induced, it can result in autophagic cell death, type II programmed cell death (PCD). The majority of the cell death due to cerebral ischemia has been attributed to apoptosis; type I PCD [17].…”

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confidence: 99%

Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation

2018

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Abstract. Ghrelin functions as a neuroprotective agent and saves neurons from various insults include ischemic injury. However, it remains to be elucidated whether ghrelin protects neuronal cells against ischemic injury-induced excessive autophagy. Autophagy is required for the maintenance of neural stem cell homeostasis. However, regarding autophagic cell death, it is commonly assumed that excessive autophagy leads to self-elimination of mammalian cells. The purpose of this study was to investigate the potential neuroprotection effects of ghrelin from excessive autophagy in adult rat hippocampal neural stem cells (NSCs). Oxygen-Glucose Deprivation (OGD) strongly induces autophagy in adult rat hippocampal NSCs. Ghrelin treatment inhibited OGD-induced cell death of adult rat hippocampal NSCs assessed by cell-counting-kit-8 assay. Ghrelin also suppressed OGD-induced excessive autophagy activity. The protective effect of ghrelin was accompanied by an increased expression levels of Bcl-2, p-62 and decreased expression level of LC3-II, Beclin-1 by Western blot. Furthermore, ghrelin reduced autophagosome formation and number of GFP-LC3 transfected puncta. In conclusion, our data suggest that ghrelin protects adult rat hippocampal NSCs from excessive autophagy in experimental stroke (oxygen-glucose deprivation) model. Regulating autophagic activity may be a potential optimizing target for promoting adult rat hippocampal NSCs based therapy for stroke.

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Berberine alleviates cardiac ischemia/reperfusion injury by inhibiting excessive autophagy in cardiomyocytes

Cited by 136 publications

References 47 publications

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

MicroRNA‐21 protects against cardiac hypoxia/reoxygenation injury by inhibiting excessive autophagy in H9c2 cells via the Akt/mTOR pathway

Pretreatment with a combination of ligustrazine and berberine improves cardiac function in rats with coronary microembolization

Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation

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