Liu Wenxiu, Zou Xingju, Zheng Yang, Zhang Yuan, Cui Guijuan, Liu Siyu, Sun Chen, Peng Cheng
State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Front Pharmacol. 2025 Mar 26;16:1526653. doi: 10.3389/fphar.2025.1526653. eCollection 2025.
Chronic heart failure (CHF) is one of the leading causes of high mortality worldwide. It is characterized by pathological hypertrophy and poses a major threat to human health. Aconiti Lateralis Radix Praeparata is widely used in ancient China to treat CHF. However, the pathology is obscured, necessitating further exploration.
Prospective targets were predicted by network analysis. A transverse aortic constriction (TAC) mice model was subsequently constructed to determine the effects of aqueous extract of Aconiti Lateralis Radix Praeparata (AEA) on CHF. The echocardiography was performed to investigate cardiac function. Histopathological analysis of cardiac tissue was conducted to assess myocardial fibrosis. Nontargeted metabolomics was performed to analyze serum metabolites. The phosphorylation level of PI3K and AKT, and downstream targets such as Bnip3, p62, Atg5, and LC3II were measured by Western blotting. , norepinephrine (NE) was used to stimulate cardiac hypertrophy. Parameters such as reactive oxygen species levels, mitochondrial membrane potential, ATP concentration, and CK/MB content were detected in H9c2 cells.
AEA significantly alleviated CHF. Network analysis indicated the participation of AKT in CHF, and was modulated by Aconiti Lateralis Radix Praeparata. , AEA administration effectively ameliorated cardiac performance, evidenced by the elevation of ejection fraction. Histopathological analysis displayed a diminishment of collagen fiber. Metabolomics analysis showed that several metabolites such as tetrahydroxycorticosterone, decylubiquinone and taurocholic acid were increased in the TAC mice serum. Additionally, the phosphorylation levels of PI3K and AKT, and expression levels of Drp1, Opa1, Bnip3, p62, Atg5 and LC3II were altered in TAC group. , NE stimulation increased the cell surface area and deteriorated mitochondrial functions in H9c2 cells. However, AEA administration partially reversed such results, and the mechanism was associated with mitophagy.
This study revealed that AEA improved cardiac function via the PI3K/AKT/Bnip3 pathway.
慢性心力衰竭（CHF）是全球高死亡率的主要原因之一。其特征为病理性肥大，对人类健康构成重大威胁。中国古代广泛使用附子治疗CHF。然而，其病理机制尚不清楚，需要进一步探索。
通过网络分析预测潜在靶点。随后构建横向主动脉缩窄（TAC）小鼠模型，以确定附子水提取物（AEA）对CHF的影响。进行超声心动图检查以研究心脏功能。对心脏组织进行组织病理学分析以评估心肌纤维化。进行非靶向代谢组学分析以分析血清代谢物。通过蛋白质免疫印迹法检测PI3K和AKT的磷酸化水平以及下游靶点如Bnip3、p62、Atg5和LC3II。用去甲肾上腺素（NE）刺激心肌肥大。在H9c2细胞中检测活性氧水平、线粒体膜电位、ATP浓度和CK/MB含量等参数。
AEA显著减轻CHF。网络分析表明AKT参与CHF，并受附子调节。AEA给药有效改善心脏功能，射血分数升高证明了这一点。组织病理学分析显示胶原纤维减少。代谢组学分析表明，TAC小鼠血清中几种代谢物如四羟基皮质酮、癸基泛醌和牛磺胆酸增加。此外，TAC组中PI3K和AKT的磷酸化水平以及Drp1、Opa1、Bnip3、p62、Atg5和LC3II的表达水平发生改变。NE刺激增加了H9c2细胞的表面积并使线粒体功能恶化。然而，AEA给药部分逆转了这些结果，其机制与线粒体自噬有关。
本研究表明AEA通过PI3K/AKT/Bnip3途径改善心脏功能。
