我们研究了苦参黄素（BAI）在MCF-7细胞系中增强卡培他滨（CAP）的抗癌潜力及其对CAP诱导的雌性Wistar大鼠心脏毒性的保护作用。体外研究涉及评估BAI和/或CAP对MCF-7细胞的细胞活力、细胞周期进程和BAX和Bcl2基因表达的影响。BAI与CAP联合治疗显著降低了MCF-7细胞的活力，提高了它们的细胞毒性效应，显著提高了G1阶段细胞群体的百分比，极大地降低了G2/M阶段细胞群体，与单独治疗相比，显著改变了BAX和Bcl2基因的mRNA表达。体内研究发现，将CAP（140 mg/kg BW）口服给成年雌性大鼠，显著提高了血清肌酸激酶-心肌带（CK-MB）、乳酸脱氢酶（LDH）、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-1β的水平以及心脏内TNF-α、IL-1β马拉酸酐（MDA）浓度，同时降低了血清和心脏的总抗氧化能力（TAC）、心脏谷胱甘肽（GSH）水平和谷胱甘肽过氧化物酶（GPx）活性，引起心脏组织的大量循环、炎症、退行性和坏死性改变。此外，CAP处理显著上调了NF-κB、TLR4、MyD88、ATF6、CHOP和JNK基因的mRNA表达。BAI（200 mg/kg BW）和CAP联合治疗显著改善了生化改变和心脏氧化还原状态和结构，同时调节了TLR4/MyD88/NF-κB通路和内质网应激。总之，BAI可以增强CAP的抗癌潜力，并缓解癌症治疗期间其心脏毒性作用。版权所有©2023年Elsevier Inc.发表。

We investigated the ability of baicalein (BAI) to enhance the anticancer potential of capecitabine (CAP) in the MCF-7 cell line and its protective effect on CAP-induced cardiotoxicity in female Wistar rats.In vitro study involved evaluating the effect of BAI and/or CAP on cell viability, cell cycle progression, and BAX and Bcl2 gene expression in MCF-7 cells. Co-treatment of BAI with CAP significantly reduced the viability of MCF-7 cells, improved their cytotoxic effect, markedly elevated the percentage of the sub-G1 population, drastically reduced the G2/M population, and significantly altered the mRNA expression of BAX and Bcl2 genes compared with each treatment alone. In vivo study revealed that the oral administration of CAP (140 mg/kg BW) to adult female rats significantly elevated the levels of serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β and cardiac TNF-α, IL-1β malondialdehyde (MDA) concentration, whereas it reduced the serum and cardiac total antioxidant capacity (TAC), level of cardiac glutathione (GSH) and activity of glutathione peroxidase (GPx) with a vast array of circulatory, inflammatory, degenerative, and necrotic alterations in the cardiac tissue. Furthermore, CAP administration significantly upregulated the mRNA expression of NF-κB, TLR4, MyD88, ATF6, CHOP, and JNK genes. Concurrent administration of BAI (200 mg/kg BW) and CAP significantly improved the biochemical alterations and cardiac oxidant/antioxidant status and architecture. In addition, it modulated the TLR4/MyD88/NF-κB pathway and endoplasmic reticulum stress.Altogether, BAI can augment the anticancer potential of CAP and alleviate its cardiotoxic effects during cancer treatment.Copyright © 2023. Published by Elsevier Inc.