Liu G, et al., J Altern Complement Integr Med 2021, 7: 179 DOI: 10.24966/ACIM-7562/100179
HSOA Journal of Alternative, Complementary & Integrative Medicine Research Article
The Effects of Ginsenoside Rg2 on Trastuzumab-Induced Cardiotoxicity Guang Liu1,2, Peipei Meng3, Yuetao Xie4 and Xiaoyong Qi2,4*
Cardiovascular department of the Fourth Hospital of Hebei Medical University,Shi Jiazhuang,Hebei Province,China
1
Graduate School,Hebei Medical University,Shi Jiazhuang,Hebei Province,China
2
The cadre ward,The 980th Hospital of the Joint Logistic Support Force of the People’s Liberation Army
3
Cardiovascular department of Hebei General Hospital,Shi Jiazhuang,Hebei Province,China
4
Abstract Objectives: Trastuzumab (TZM) shows significant effects in early-stage HER2-positive breast cancer, but it is also followed by severe cardiotoxicity. Ginsenoside Rg2 has been demonstrated usefully against myocardial injury and apoptosis. However, whether ginsenoside Rg2 can protect cardiomyocytes with TZM-induced toxicity is not clear. The study is to investigate its possible mechanism. Methods:30 wistar male rats were divided in 3 groups (control group, TZM group and TZM+Rg2 group), cardiac ultrasound was performed before and after the experiment; cardiomyocytes (H9C2) was divided in 3 groups (control group, TZM group and TZM+Rg2 group), Annexin V test and Western blot were performed in the experiment. Results: Ginsenoside Rg2 inhibited the deterioration of cardiac function in rats, ginsenoside Rg2 inhibited cardiomyocyte apoptosis, increased the expression of Caspase-3、Caspase-9 and BAX in cell experiment. Conclusions: Ginsenoside Rg2 could protect cardiomyocytes in TZM-induced toxicity and it might be via inhibiting cell apoptosis. Keywords: Breast cancer; Cardiotoxicity; Cell apoptosis; Ginsenoside Rg2; Trastuzumab
shows significant effects in early-stage breast cancer [1]. I the majority of patients with HER2-positive breast cancer, TZM has a significantly increasing in the overall survival [2].. However, TZM has a following cardiac side effects, including QTprolongation, bradycardia, hypertension, thromboembolic disease, congestive heart failure and ischemic heart disease, despite its beneficial effects [3,4]. Ginseng (Panax ginseng) is a traditional Chinese herbal medicine that has been widely used for thousands of years in East Asia, including China, Korea and Bhutan [5]. Ginsenoside is extracted from ginseng and plays the most important role among its components, including anti-inflammatory, antioxidant, anticancer, immunomodulatory and anti-stress effects [6-8]. Ginsenoside Rg2 is one compound of ginsenoside and has been proved multiple roles, including improving neurological performance, enhancing memory and exhibiting protective effects against hydrogen peroxide-induced injury and apoptosis in human cardiomyocytes [9-12]. This study aimed to investigate whether ginsenoside Rg2 could protect HCMs against TZM-induced toxicity in vitro and cardiac function in animal experiment.
Materials and Methods Animal experiments The experiment was approved by the Animal Care and Use Committee of Hebei Medical University; they were in compliancewiththeNationalInstitutesofHealthGuideforCareandUseofLaboratoryAnimals. 30 male wistar rats (160±10g) were randomly divided into 3 groups (n=10 per group):control group, TZM group and TZM+Rg2 group. TZM was given by intraperitoneal injection with a dose of 12mg/kg, then at a dose of 6mg/kg per day for 6 consecutive days, the ginsenoside Rg2 was given by intraperitoneal injection with a dose of 15mg/kg, the subsequent experiments were conducted after 24 hours, the control group was injected with the same dose of normal saline. Cardiac ultrasound was performed in the last day and Left Ventricular End-diastolic Diameter (LVEDD), Left Ventricular End-systolic Diameter (LVESD), Left Ventricular Ejection Fraction (LVEF) and Left Ventricular Fractional Shortening (LVFS) were recorded.
Introduction
Cell experiments
Trastuzumab (TZM) is a humanized monoclonal antibody that targets on Human Epidermal growth factor receptor 2 (HER2) and
Human primary HCMs (Applied Biological Materials, Inc.) were cultured in DMEM (Sigma‑Aldrich; Merck KGaA) containing 10% FBS (Thermo Fisher Scientific, Inc.), maintained at 37℃ and 5% CO2. They were divided in 3 groups as the same as the rats.TZM group was processed by TZM with a dose of 10μg/mL for 24h,TZM+Rg2 group was preprocessed by Rg2[purity>98% (by high-performance liquid chromatography analysis); MedChemExpress) with a dose of 0. 025mmol/ L for 24h, then the subsequent experiment was performed, the control was processed by the same dose of DMSO. Annex in V TEST and Western blotting were performed after TZM administration in 24h.
*Corresponding author: Xiaoyong Qi, Cardiovascular department of Hebei General Hospital,Shi Jiazhuang,Hebei Province,China, Tel: +86 031186095739; E-mail: 47126458@qq.com Citation: Liu G, Qi X (2021) The Effects of Ginsenoside Rg2 on Trastuzumab-Induced Cardiotoxicity. J Altern Complement Integr Med 7: 179. Received: June 04, 2021; Accepted: June 09, 2021; Published: June 16, 2021 Copyright: © 2021 Liu G, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Cell proliferation assay: HCMs (5x103 cells/well) were seeded in a 96-well plate in triplicate. The cells were subsequently treated with