25-Hydroxyl-protopanaxatriol protects against H2O2-induced H9c2 cardiomyocytes injury via PI3K/Akt pathway and apoptotic protein down-regulation
Authors: Guangyue Su
Yuqing Zhao
Han Dong
Yuehui Wang
Qi Sun
Huiying Zhao
Zhihao Wang
Zhiguo Zhang
Journal: Biomedicine & Pharmacotherapy (2018)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: 25-Hydroxyl-protopanaxatriol; Apoptosis; H9c2 myocardial cells; Oxidative stress injury; PI3K/Akt pathway.
Affiliations: Department of Geriatrics, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China., School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China., Diagnostic and Treatment Center for Cardiovascular Diseases, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China., Department of Geriatrics, The First Hospital of Jilin University, Changchun, 130021, People's Republic of China. Electronic address: ., School of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China; Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China. Electronic address: ., The First Hospital of Jilin University, Changchun, 130021, People's Republic of China; Department of Cardiology, No.202 Hospital of China PLA, No 5 Guangrong Road, Heping District, Shenyang, 110812, People's Republic of China. Electronic address: .

Abstract:  Oxidative stress injury and apoptosis are the main mechanisms of myocardial ischemia-reperfusion injury (MI/RI). Compounds with anti-oxidant properties can treat MI/RI. Therefore, identification of natural antioxidants such as herbs or botanical drugs is an ideal strategy to develop safe and effective anti-MI/RI drugs. Cardioprotective effects of Ginseng are well documented and are attributable to its anti-oxidant, anti-inflammatory, anti-tumorigenic, anti-arrhythmic, anti-ischemic properties. Ginseng monomer 20¬Æ-dammarane -3 beta,6 alpha,12 beta,20,25-pentol(25-hydroxyl-Protopanaxatriol,25-OH-PPT), a novel compound, which belongs to panaxatriol category, is extracted from the leaves and stem of ginseng. It was first investigated for its anti-tumorigenic properties. In this study, we explored whether 25-OH-PTT plays a role in antioxidant stress injury and anti-apoptosis in cardiomyocytes. We also explored the mechanisms in order to provide a theoretical basis to develop 25-OH-PPT as a new drug for treatment of MI/RI. First, we used H2O2 to induce H9c2 cardiomyocytes in vitro resulting in an oxidative stress injury model and pretreated with 25-OH-PPT. Secondly, we examined the viability of H9c2 cells by MTT assay, the reactive oxygen species (ROS) content and mitochondrial membrane potential by flow cytometry as well as cell apoptosis by flow cytometry Annexin-FITC/PI and Hoechst 33258 staining. Furthermore, we pretreated H9c2 cells with PI3K inhibitor, LY294002, and observed the above phenomenon. Lastly, we examined the expressions of proteins related to the PI3K/Akt signaling pathway and the apoptotic proteins. We found that 25-OH-PPT can protect H9c2 cells against H2O2-induced injury, decrease apoptosis of H9c2 cells and ROS generation, and increase the mitochondrial membrane potential. It can also upregulate the protein expressions of p-Akt, p-eNOS, and Bcl-2 and down-regulate apoptotic proteins Bax and Caspase-3. Our results indicate that 25-OH-PPT inhibits H2O2-induced H9c2 cardiomyocytes injury through PI3K/Akt pathway. It may become a potential safe and effective traditional Chinese medicine monomer for treatment of MI/RI. 

Retracted: No

PubPeer comments:
 Fig 2C.  The ROS content ... of H9c2 cardiomyocytes in four groups (n = 3): The ROS content in H9c2 cardiomyocytes decreased ... in the 250 u03bcM 25- OH-PPT group, while an opposite effect was observed in the LY294002 group . A minor error: A panel has been repeated.  , 
 Dear Hoya Camphorifolia, We appreciate your interest in our work and your efforts to ensure the accuracy of the scientific record, which also extremely important to us. Upon receipt of your query, we regarded the solution of the problem as our top priority and took immediate action to carefully re-check our manuscripts, raw data and experimental records. Based on our analysis to date, the error was because of that we merged the model group (Fig. 2C-b) by mistake, and the correct figure is attached below. We have also contacted with the journalu2019s editorial office to correct this issue. I d like to add that I remain confident in the validity, reliability and reproducibility of the scientific conclusions in this article. Although it was an unintentional mistake, I m deeply sorry for the negligence in my work and any incovenience that may have been caused. We regard it as a valuable learning opportunity and lesson. We will check our publications more carefully and make a greater contribution to safeguarding scientific accuracy and integrity in the future. Thank you for your attention and help. Sincerely Zhihao Wang  , 
 #2 Thank you for a helpful and constructive response! ,