title: Protective effect of berberine against myocardial ischemia reperfusion injury: role of Notch1/Hes1-PTEN/Akt signaling.
abstract: Berberine (BBR) confers cardioprotective effect against myocardial ischemia reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also reduces MI/RI. We hypothesize that BBR may protect against MI/RI by modulating Notch1/Hes1-Phosphatase and tensin homolog deleted on chromosome ten (PTEN)/Akt signaling. In this study, male Sprague-Dawley rats were exposed to BBR treatment (200 mg/kg/d) for 2 weeks and then subjected to MI/RI. BBR significantly improved cardiac function recovery and decreased myocardial apoptosis, infarct size, serum creatine kinase and lactate dehydrogenase levels. Furthermore, in cultured H9c2 cardiomyocytes, BBR (50 μmol/L) attenuated simulated ischemia/reperfusion-induced myocardial apoptosis. Both in vivo and in vitro study showed that BBR treatment up-regulates Notch1 intracellular domain, Hes1, Bcl-2 expression and p-Akt/Akt ratio, down-regulates Bax Caspase-3 and cleaved Caspase-3 expression. However, the anti-apoptotic effect conferred by BBR was blocked by Notch1 siRNA, Hes1 siRNA or LY294002 (the specific inhibitor of Akt signaling) in the cultured cardiomyocytes. In summary, our results demonstrate that BBR treatment attenuates MI/RI by modulating Notch1/Hes1-PTEN/Akt signaling.
authors.affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, 127 Changle West Road, Xi'an, 710032, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Yu
authors.forename: Feijiang
authors.initials: F
authors.lastname: Li
authors.forename: Guolong
authors.initials: G
authors.lastname: Zhao
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhenxiao
authors.initials: Z
authors.lastname: Jin
authors.forename: Mengen
authors.initials: M
authors.lastname: Zhai
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhao
authors.forename: Wensheng
authors.initials: W
authors.lastname: Chen
authors.forename: Weixun
authors.initials: W
authors.lastname: Duan
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001599:Berberine / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism*; D008297:Male; D009025:Morpholines / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D051881:Receptor, Notch1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D001599:Berberine; D002867:Chromones; D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; D009025:Morpholines; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; D034741:RNA, Small Interfering; D051881:Receptor, Notch1; D000072056:Transcription Factor HES-1; C489735:Hes1 protein, rat; C497763:Notch1 protein, rat; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C487216:Pten protein, rat