Biochanin a Alleviated Doxorubicin-Induced Cardiotoxicity but Did not Interfere With the Antitumor Effect of Doxorubicin.

IF 6.1 2区 医学 Q1 CHEMISTRY, MEDICINAL
Yijin Yang, Zhenyu Feng, Fengying Zhou, Xuyang Sun, Jinshu Shang, Ningning Zhang, Yunlong Xia, Yunpeng Xie
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引用次数: 0

Abstract

Background and aim: Doxorubicin (DOX)-induced cardiotoxicity (DIC) by the chemotherapeutic drug seriously affects the prognosis of patients with cancer. Therefore, it is significant to actively explore the underlying mechanisms of DIC and develop safe and effective adjuvant therapies to improve DIC. As a traditional Chinese medicine monomer, BCA can treat cardiovascular diseases. However, whether BCA is able to inhibit DOX-induced myocardial injury without affecting its anticancer effect is unclear.

Experimental procedure: We divided tumor-bearing mice into four groups, constructed a heart failure model by administering DOX, and treated with BCA. Histopathological staining was performed (WGA, HE, IF, IHC, etc.), WB, qPCR, and serum detection of SOD and MDA. In vitro experiments, the effects of BCA and DOX in both kinds of cells were demonstrated by various experiments in primary cardiomyocytes and tumor cells panc02 of neonatal rats.

Key results: The results showed that BCA could inhibit DOX-induced abnormal cardiac function in mice, improve heart failure, and inhibit the expression of ANP and BNP. It inhibited the level of myocardial oxidative stress and reduced the number of myocardial vacuolation and the degree of myocardial fibrosis in mice. BCA reduced DOX-induced oxidative stress in NRCMs. In terms of tumors, BCA cooperates with DOX to inhibit the occurrence and development of panc02 and reduce the body weight of tumors. It inhibited the expression of PCNA and promoted the expression of BAX. In vitro experiments, BCA cooperated with DOX to inhibit the proliferation and metastasis of panc02.

Conclusions and implications: To sum up, BCA can affect the occurrence and development of DOX-induced myocardial injury through multiple targets and pathways and does not interfere with the anti-tumor effect of DOX. This study seeks new drugs for DOX-induced myocardial injury and provides new ideas for the treatment of inhibiting DOX-induced myocardial injury and the research of related diseases.

生物茶素a减轻了阿霉素引起的心脏毒性,但不干扰阿霉素的抗肿瘤作用。
背景与目的:化疗药物多柔比星(DOX)诱导的心脏毒性(DIC)严重影响肿瘤患者的预后。因此,积极探索DIC的潜在机制,开发安全有效的辅助治疗方法来改善DIC具有重要意义。BCA是一种中药单体,具有治疗心血管疾病的作用。然而,BCA是否能够抑制dox诱导的心肌损伤而不影响其抗癌作用尚不清楚。实验步骤:将荷瘤小鼠分为4组,给予DOX建立心衰模型,BCA治疗。进行组织病理学染色(WGA、HE、IF、IHC等)、WB、qPCR、血清SOD、MDA检测。在体外实验中,通过对新生大鼠原代心肌细胞和肿瘤细胞panc02的实验,证实了BCA和DOX对两种细胞的作用。关键结果:结果显示BCA能抑制dox诱导的小鼠心功能异常,改善心力衰竭,抑制ANP和BNP的表达。抑制小鼠心肌氧化应激水平,减少心肌空泡次数,降低心肌纤维化程度。BCA降低dox诱导的nrcm氧化应激。在肿瘤方面,BCA与DOX协同抑制panc02的发生发展,减轻肿瘤的体重。抑制PCNA表达,促进BAX表达。体外实验中,BCA与DOX联合抑制panc02的增殖和转移。结论及意义:综上所述,BCA可通过多靶点、多途径影响DOX诱导心肌损伤的发生发展,且不干扰DOX的抗肿瘤作用。本研究寻求dox致心肌损伤的新药,为抑制dox致心肌损伤的治疗及相关疾病的研究提供新的思路。
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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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