Tang Dachao, Jin Hu, Lin Meise, Jiang Fuling, Wu Jing
Department of Cardiovascular Medicine, Wenzhou Hospital of Traditional Chinese Medicine Wenzhou 325000, Zhejiang, China.
Am J Transl Res. 2025 Feb 15;17(2):806-817. doi: 10.62347/KWRF2732. eCollection 2025.
To investigate the effects of naturally derived leonurine (Leo) on doxorubicin (Dox)-induced myocarditis and analyze its potential mechanisms.
Dox was intraperitoneally injected to establish a myocardial injury model in mice. The effect of Leo on inflammatory cytokine levels in myocardial tissue was assessed by ELISA. Pathological changes in myocardial tissue and apoptosis in myocardial cells were observed using hematoxylin-eosin (HE) and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Protein levels were analyzed by Western blot (WB). Mouse myocardial H9c2 cells were divided into control group, Dox group, Leo (10 μmol/L) + Dox group, and Leo (20 μmol/L) + Dox group. Cell viability was assessed using Cell Counting Kit-8 (CCK8), and the levels of inflammatory cytokines were measured. The oxidation level and protein levels in H9c2 cells were also detected.
Leo significantly reduced the levels of inflammatory cytokines in both serum and cell culture supernatant. Additionally, Leo also decreased the levels of inflammatory cytokines in cardiac tissue. Moreover, Leo suppressed Dox-induced myocardial cell apoptosis by modulating the BCL2 signaling pathway. In vitro studies revealed that both inflammatory cytokines and oxidative stress markers were decreased after treatment with Leo.
Leo exerts significant cardioprotective effects through anti-inflammatory mechanisms, likely mitigating Dox-induced myocardial inflammation by inhibiting the activation of MAPK/ERK pathways. These findings highlight Leo's potential as a promising cardioprotective agent, underscoring its therapeutic promise.
研究天然来源的益母草碱（Leo）对阿霉素（Dox）诱导的心肌炎的影响，并分析其潜在机制。
通过腹腔注射Dox建立小鼠心肌损伤模型。采用酶联免疫吸附测定（ELISA）评估Leo对心肌组织中炎性细胞因子水平的影响。使用苏木精-伊红（HE）染色和末端脱氧核苷酸转移酶介导的dUTP缺口末端标记（TUNEL）染色观察心肌组织的病理变化和心肌细胞凋亡情况。通过蛋白质免疫印迹法（WB）分析蛋白质水平。将小鼠心肌H9c2细胞分为对照组、Dox组、Leo（10 μmol/L）+ Dox组和Leo（20 μmol/L）+ Dox组。使用细胞计数试剂盒-8（CCK8）评估细胞活力，并检测炎性细胞因子水平。同时检测H9c2细胞中的氧化水平和蛋白质水平。
Leo显著降低了血清和细胞培养上清液中炎性细胞因子的水平。此外，Leo还降低了心脏组织中炎性细胞因子的水平。而且，Leo通过调节BCL2信号通路抑制Dox诱导的心肌细胞凋亡。体外研究表明，用Leo处理后炎性细胞因子和氧化应激标志物均降低。
Leo通过抗炎机制发挥显著的心脏保护作用，可能通过抑制MAPK/ERK通路的激活减轻Dox诱导的心肌炎症。这些发现凸显了Leo作为一种有前景的心脏保护剂的潜力，强调了其治疗前景。
