State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China.
Toxicon. 2024 May 6;242:107693. doi: 10.1016/j.toxicon.2024.107693. Epub 2024 Mar 21.
Aconitine is the main active component of Aconitum plants. Although aconitine has effects that include strengthening the heart, analgesia, anti-tumor, and immune-regulating effects, aconitine has both efficacy and toxicity, especially cardiotoxicity. Severe effects can include arrhythmia and cardiac arrest, which limits the clinical application of aconitine-containing traditional Chinese medicine. Ginsenoside Rb1(Rb1) is mainly found in plants, such as ginseng and Panax notoginseng, and has cardiovascular-protective and anti-arrhythmia effects. This study aimed to investigate the detoxifying effects of Rb1 on aconitine cardiotoxicity and the electrophysiological effect of Rb1 on aconitine-induced arrhythmia in rats. Pathological analysis, myocardial enzymatic indexes, and Western blotting were used to investigate the ameliorating effect of Rb1 on aconitine cardiotoxicity. Optical mapping was used to evaluate the effect of Rb1 on action potential and calcium signaling after aconitine-induced arrhythmia. Rb1 inhibited pathological damage caused by aconitine, decreased myocardial enzyme levels, and restored the balance of apoptotic protein expression by reducing the expression of Bax and cleaved caspase 3 and increasing the expression of Bcl-2, thereby reducing myocardial damage caused by aconitine. Rb1 also reduced the increase in heart rate caused by aconitine, accelerated action potential conduction and calcium signaling, and reduced the dispersion of action potential and calcium signal conduction. Rb1 reduced the cardiotoxicity of aconitine by attenuating aconitine-induced myocardial injury and inhibiting the aconitine-induced retardation of ventricular action potential and calcium signaling in rats.
乌头碱是乌头属植物的主要活性成分。虽然乌头碱具有强心、镇痛、抗肿瘤、免疫调节等作用，但乌头碱既有疗效又有毒性，尤其是心脏毒性。严重的影响包括心律失常和心脏骤停，这限制了含乌头碱的中药的临床应用。人参皂苷 Rb1（Rb1）主要存在于植物中，如人参和三七，具有心血管保护和抗心律失常作用。本研究旨在探讨 Rb1 对乌头碱心脏毒性的解毒作用以及 Rb1 对大鼠乌头碱诱导心律失常的电生理作用。通过病理分析、心肌酶指标和 Western blot 探讨 Rb1 对乌头碱心脏毒性的改善作用。光学映射用于评估 Rb1 对乌头碱诱导心律失常后动作电位和钙信号的影响。Rb1 抑制乌头碱引起的病理损伤，降低心肌酶水平，并通过降低 Bax 和 cleaved caspase 3 的表达和增加 Bcl-2 的表达来恢复凋亡蛋白表达的平衡，从而减轻乌头碱引起的心肌损伤。Rb1 还降低了乌头碱引起的心率增加，加速了动作电位和钙信号的传导，并降低了动作电位和钙信号传导的离散度。Rb1 通过减轻乌头碱引起的心肌损伤和抑制乌头碱引起的大鼠心室动作电位和钙信号传导延迟，减轻了乌头碱的心脏毒性。
