Chen Weiying, Luo Xiang, Li Wentao, Li Xiaocui, Wang Ying, Zhang Rong, Liu Bo, Zhu Lijun, Liu Zhongqiu, Cheng Yuanyuan
Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China; The Second Clinical Medicial College, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
J Ethnopharmacol. 2025 Feb 27;342:119418. doi: 10.1016/j.jep.2025.119418. Epub 2025 Jan 27.
Xinbao pill (XBP) is a renowned Chinese patent medicine, primarily efficacious in warming and nourishing the heart and kidneys, supplementing Qi to boost Yang, and promoting blood circulation to remove blood stasis. XBP has been utilized for the treatment of chronic heart failure (CHF) for nearly 30 years, but the lack of clarity regarding the active ingredients of XBP against CHF has hindered its clinical application and further promotion.
To comprehensively elucidate the efficacy-specific ingredients and potential mechanism of XBP against CHF.
The efficacy, chemical profiling and pharmacokinetics of XBP was assessed in a CHF model rat. The anti-CHF mechanism of the mixture of the likely active ingredients was clarified by targeted metabolomics and western blotting analysis.
XBP alleviated CHF by enhancing cardiac function, reducing NT-pro BNP, mitigating myocardial damage and degrading extracellular collagen. Following XBP administration, ginsenosides exposed relatively abundant in sham or CHF rats. Ginsenoside Rg1 and notoginsenoside R1 showed downward trends in AUC values in CHF group, accompanied by increasing trends in CL/F values. Moreover, CHF rats presented significantly elevated levels of ginsenoside Rg1, ginsenoside Rg2 and notoginsenoside R1 in heart. The mixture of ginsenoside Rg1, ginsenoside Rg2 and notoginsenoside R1 demonstrated remarkable efficacy in ameliorating CHF as XBP did. Notably, these three compounds were predominantly localized in mitochondria and exhibited significant potential to enhance mitochondrial homeostasis by inhibiting heme synthesis pathway-mediated decomposition of succinyl CoA.
Our research provides valuable insights that ginsenoside Rg1, ginsenoside Rg2 and notoginsenoside R1 may constitute the anti-CHF active ingredients of XBP for facilitating mitochondrial homeostasis by the suppression of heme synthesis to increase succinyl CoA.
心宝丸（XBP）是一种著名的中成药，主要功效为温养心肺、益气助阳、活血化瘀。XBP用于治疗慢性心力衰竭（CHF）已近30年，但XBP治疗CHF的有效成分尚不明确，这阻碍了其临床应用和进一步推广。
全面阐明XBP治疗CHF的药效特异性成分及潜在机制。
在CHF模型大鼠中评估XBP的疗效、化学图谱和药代动力学。通过靶向代谢组学和蛋白质印迹分析阐明可能的活性成分混合物的抗CHF机制。
XBP通过增强心功能、降低NT-pro BNP、减轻心肌损伤和降解细胞外胶原纤维来缓解CHF。给予XBP后，人参皂苷在假手术或CHF大鼠中相对含量较高。人参皂苷Rg1和三七皂苷R1在CHF组中的AUC值呈下降趋势，同时CL/F值呈上升趋势。此外，CHF大鼠心脏中人参皂苷Rg1、人参皂苷Rg2和三七皂苷R1的水平显著升高。人参皂苷Rg1、人参皂苷Rg2和三七皂苷R1的混合物在改善CHF方面显示出与XBP相当的显著疗效。值得注意的是，这三种化合物主要定位于线粒体，并且通过抑制血红素合成途径介导的琥珀酰辅酶A分解，具有增强线粒体稳态的显著潜力。
我们的研究提供了有价值的见解，即人参皂苷Rg1、人参皂苷Rg2和三七皂苷R1可能构成XBP治疗CHF的活性成分，通过抑制血红素合成增加琥珀酰辅酶A来促进线粒体稳态。
