Retracted Article: Vitexin mitigates myocardial ischemia reperfusion-induced damage by inhibiting excessive autophagy to suppress apoptosis via the PI3K/Akt/mTOR signaling cascade
Authors: Zhaobin Tang
Lei Yang
Xuesong Zhang
Journal: RSC Advances (2017)
Discipline: CHEMISTRY
Keywords: Myocardial ischemia reperfusion injury; Vitexin; Cardioprotective effect; Apoptosis; Autophagy
Affiliations: Department of Cardiology, The First Hospital of Zibo, China, Hospital of Laiwu Steel Group, Liaocheng People's Hospital, Liaocheng

Abstract: Myocardial ischemia reperfusion (MI/R) injury is reported to induce apoptosis and autophagy of myocardial cells and contribute to adverse cardiovascular outcomes. Vitexin, a flavonoids compound, exhibited anti-inflammatory, anti-oxidative and antitumor effects in various studies. Here, we investigated the cardioprotective effect and underlying mechanism of vitexin treatment in MI/R injury in vivo and in vitro. We found that vitexin decreased the high cell apoptosis rate caused by MI/R injury significantly in a dose-dependent manner. The expression of cleaved Caspase-3 and Bax was down-regulated and the expression of Bcl-2 was up-regulated by vitexin compared with MI/R model group, indicating that vitexin suppressed apoptosis of rat cardiomyocytes H9c2 cells in MI/R injury. The concentrations of LDH, CK and MDA were decreased while the concentration of SOD was increased by vitexin during MI/R injury. Moreover, vitexin also suppressed autophagy of H9c2 cells in MI/R injury by down-regulating the expression of Beclin1 and LC3I/II while up-regulating the expression of p62. Activation of autophagy by Rapa significantly increased cleaved Caspase-3, Bcl-2 expression and the concentration of LDH, CK, MDA while decreased the concentration of SOD, indicating that vitexin inhibited autophagy to suppress apoptosis of H9c2 cells in MI/R injury. The co-treatment of PI3K inhibitor LY294002 reversed the inhibition on apoptosis and autophagy by vitexin, suggesting that vitexin inhibited apoptosis and autophagy to ameliorate MI/R injury through activation of PI3K/Akt/mTOR signaling pathway. We also constructed MI/R animal model using C57BL/6 mice to investigate the cardioprotective effects of vitexin in vivo. We observed that vitexin mitigated MI/R injury by decreasing the concentrations of LDH, CK and MDA, increasing the concentration of SOD, and counteracting the irregular pathological changes induced by MI/R injury dose-dependently. Vitexin also suppressed apoptosis and autophagy in myocardium cells of C57BL/6 mice in MI/R injury via activation of PI3K/Akt/mTOR signaling pathway. In conclusion, vitexin mitigated MI/R injury by inhibiting apoptosis and excessive autophagy via the PI3K/Akt/mTOR signaling pathway.

Retracted: Yes

PubPeer comments:
 Fig 2A.  Vitexin suppresses apoptosis of H9c2 cells in MI R injury. H9c2 cells were divided into control group, MI R model group and MI R + vitexin treated group (50 u03bcM, 100 u03bcM and 200 u03bcM respectively) . ![file] The grey rectangle (panel 2) highlights similarity to the 4th panel from Fig 4B of [Zhang et al (2018)] .  Suppressing TOP2A expression induces colon cancer cell apoptosis. A, HCT116 and (B) SW480 cells were transfected with indicated siRNA. After 48 h of culture, cells were collected, stained with Annexin V PI and analyzed by flow cytometry ![file] Black and light grey rectangles (panels 4 and 5) highlight similarities to first and second panels of Fig 3A from [Li et al (2019)] , ![] and the HT29 Control panel in Fig 1F of [Yu Chai (2017)] . ![] Yu Chai (2017) was  Received 2017 Mar 6; Accepted 2017 Aug 3 . The present paper was  Submitted 06 Nov 2017; Accepted 10 Dec 2017; First published 15 Dec 2017 . , 
 Fig 6E.  Cardioprotective effect of vitexin in vivo. C57BL 6 mice were divided into Sham group, MI R group and MI R + vitexin treated group (2, 4, 6 mg kgu22121 respectively). ... (E) Hematoxylin and eosin (H E) staining was used to observe histopathologic changes in mice hearts . Two panels overlap. ![file] I have doubled the width of the Figure, as the horizontal compression of the published version was a hindrance to examination. , 
 Fig 5 A, D, J. Increasing the contrast (below) emphasises the texture of the background. ![file] The texture is of interest partly because it is repetitive, and partly because of the sharp-edged discontinuities, which I have tried to emphasise at right. ![file] , 
 Retracted [21 January 2021] . ------------------------------------------ The Royal Society of Chemistry hereby wholly retracts this RSC Advances article due to concerns with the reliability of the data. The images in the article were screened by an image integrity expert who confirmed that some of the western blot images in this paper had been duplicated in other articles. There are no common authors between the papers. The control bands (GAPDH) presented in Fig. 2C and 4G of this paper are identical. In addition, these bands are identical to the western blot control bands (GAPDH) presented in Fig. 4A of ref. 1. One of the blots in the control band (GAPDH) in Fig. 2C has also been reused as a blot in Fig. 3D of ref. 2. The p62 band in Fig. 4A has been duplicated as the Col II band in Fig. 3B of ref. 2. The authors were asked to provide the raw data for this article but did not respond. Given the significance of the concerns about the validity of the data, and the lack of raw data, the findings presented in this paper are not reliable. The authors have been informed but have not responded to any correspondence regarding the retraction. Signed: Laura Fisher, Executive Editor, RSC Advances Date: 7th January 2021 References H. Yang and S. Wu , RSC Adv., 2018, 8 , 21816 u201421822 RSC . B. Zhu , X. Wang and J. Teng , RSC Adv., 2018, 8 , 36422 u201436429 RSC . ,