Guangzhou University of Chinese Medicine, Guangzhou, China.
Guangzhou University of Chinese Medicine, Guangzhou, China; Innovation Research Center, Shandong University of Chinese Medicine, Jinan, China.
J Ethnopharmacol. 2024 Dec 5;335:118685. doi: 10.1016/j.jep.2024.118685. Epub 2024 Aug 9.
Chronic heart failure (CHF) is a severe consequence of cardiovascular disease, marked by cardiac dysfunction. Jin-Xin-Kang (JXK) is a traditional Chinese herbal formula used for the treatment of CHF. This formula consists of seven medicinal herbs, including Ginseng (Ginseng quinquefolium (L.) Alph.Wood), Astragali Radix (Astragalus membranaceus (Fisch.) Bunge), Salvia miltiorrhiza (Salvia miltiorrhiza Bunge), Descurainiae Semen Lepidii Semen (Descurainia sophia (L.) Webb ex Prantl), Leonuri Herba (Leonurus japonicus Houtt.), Cinnamomi Ramulus (Cinnamomum cassia (L.) J.Presl), and Ilex pubescens (Ilex pubescens Hook. & Arn.). Its clinical efficacy has been validated through prospective randomized controlled studies. However, the specific mechanisms of action for this formula have yet to be elucidated.
This study aimed to investigate the effect of JXK on mitochondrial function and its mechanism in the treatment of CHF.
JXK components were qualitatively analyzed using UPLC-Q-Orbitrap-MS. HF was induced in mice via transverse aortic constriction (TAC). After successful model establishment, lyophilized JXK-L (4.38 g/kg) and JXK-H (13.14 g/kg) were administered for 8 weeks. In vitro, hypertrophic myocardium was induced using angiotensin II (Ang II) for 48 h, followed by JXK-L and JXK-H treatment. Network pharmacology and molecular docking techniques were used to predict the relevant targets of JXK. Cardiac function, serum markers, and histopathological changes were evaluated to assess cardiac function. Immunofluorescence of Tomm20, mitochondrial membrane potential, and ROS were measured to assess mitochondrial dysfunction. Protein expression of calcineurin (CaN) and Drp1 in the myocardium was assessed by Western blot analysis.
We detected that the active components of JXK include terpenes, glycosides, flavonoids, amino acids, and alkaloids, among others. In mice with CHF, JXK improved cardiac function and reversed ventricular remodeling. Network pharmacology indicated that JXK can inhibit the calcium signaling pathway. The molecular docking results demonstrated that the active components of JXK effectively bind with CaN. Both in vitro and in vivo experiments confirmed that JXK regulated the CaN/Drp1 pathway and alleviated mitochondrial dysfunction.
JXK can inhibit the CaN/Drp1 pathway to improve mitochondrial function, and consequently treat CHF.
ETHNOPHARMACOLOGICAL 相关性：慢性心力衰竭 (CHF) 是心血管疾病的严重后果，其特征为心脏功能障碍。金心康 (JXK) 是一种用于治疗 CHF 的中药配方。该配方由七种草药组成，包括人参（西洋参）、黄芪、丹参、葶苈子、益母草、桂皮和毛冬青。其临床疗效已通过前瞻性随机对照研究得到验证。然而，该配方的具体作用机制尚未阐明。
本研究旨在探讨 JXK 对 CHF 治疗中线粒体功能的影响及其机制。
采用 UPLC-Q-Orbitrap-MS 对 JXK 成分进行定性分析。通过横主动脉缩窄 (TAC) 在小鼠中诱导 HF。成功建立模型后，给予冻干 JXK-L（4.38 g/kg）和 JXK-H（13.14 g/kg）治疗 8 周。在体外，使用血管紧张素 II (Ang II) 诱导肥厚心肌 48 h，然后用 JXK-L 和 JXK-H 处理。采用网络药理学和分子对接技术预测 JXK 的相关靶点。通过评估心功能、血清标志物和组织病理学变化来评估心功能。通过免疫荧光法测定 Tomm20、线粒体膜电位和 ROS，评估线粒体功能障碍。通过 Western blot 分析评估心肌中钙调神经磷酸酶 (CaN) 和 Drp1 的蛋白表达。
我们检测到 JXK 的活性成分包括萜类、糖苷、黄酮类、氨基酸和生物碱等。在 CHF 小鼠中，JXK 改善了心功能并逆转了心室重构。网络药理学表明，JXK 可以抑制钙信号通路。分子对接结果表明，JXK 的活性成分可有效与 CaN 结合。体内外实验均证实，JXK 调节 CaN/Drp1 通路，缓解线粒体功能障碍。
JXK 可抑制 CaN/Drp1 通路，改善线粒体功能，从而治疗 CHF。
