Chinese Journal of Pharmacovigilance ›› 2026, Vol. 23 ›› Issue (6): 621-629.
DOI: 10.19803/j.1672-8629.20260430

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Roles of Butu Decoction in Improving Heart Failure in Rats by Activating AKT/Bcl-2 Signaling Axis and Inhibiting Cardiomyocyte Apoptosis

LI Yanjun1, LIU Chengxiang2, TANG Bo1, LIU Yi3, ZHANG Jiuliang3, JIANG Guochen4,*, BAI Xue5#   

  1. 1Department of Cardiology, Rizhao Hospital of Traditional Chinese Medicine, Rizhao Shandong 276800, China;
    2Department of Neurology, Rizhao Hospital of Traditional Chinese Medicine, Rizhao Shandong 276800, China;
    3Cardiology Department of Integrated Traditional Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing 100029, China; 4Department of Traditional Chinese Medicine, the First Hospital of Tsinghua University, Beijing 100016, China;
    5Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Disease, Beijing 100700, China
  • Received:2026-05-27 Online:2026-06-15 Published:2026-06-18

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Abstract: Objective To explore the effect of Butu decoction on cardiac function of SD rats with heart failure (HF) and its molecular mechanism against cardiomyocyte apoptosis via the AKT/Bcl-2 signaling pathway. Methods Left anterior descending branch ligation was performed on male SD rats to establish an HF model. The surviving model rats were randomly divided into a model group (n=10), a Butu decoction group (n=10), and an enalapril maleate group (n=10). A sham surgery group was also established (n=10). Four weeks after intragastric administration, the cardiac function was detected via ultrasound. HE staining was used to observe myocardial histopathological changes, and Masson staining the degree of myocardial fibrosis. ELISA was employed to detect BNP contents in serum. Network pharmacology combined with molecular docking was used to identify the potential core targets and active components of Butu decoction against HF. TdT-mediated dUTP Nick-End Labeling (TUNEL) was adopted to determine the apoptosis rate of cells in regions bordering the infarction in rats. The protein expression levels of AKT1, pAKT1, Bax, Bcl-2 and Caspase-3 in these regions were detected via Western Blot. Results Results of animal experiments showed that the levels of LVESD and LVEDD in the Butu decoction group significantly decreased compared with the model group (P<0.01), while those of LVEF and LVFS significantly increased (P<0.01). HE staining suggested that the pathomorphology of rats in the Butu decoction group improved compared to the model group. The degree of myocardial fibrosis and the serum levels of BNP in the Butu decoction group were significantly reduced (P<0.01). Network pharmacology and molecular docking found that the main active components of Butu decoction, such as luteolin and quercetin, showed strong binding activity to AKT1, a core target regulating cell apoptosis and growth. Mechanistic studies suggested that Butu decoction significantly reduced the apoptosis rate of cardiomyocytes in regions bordering the infarction (P<0.01). This decoction had no obvious effect on the total protein level of AKT1, but markedly upregulated the expression of pAKT1 (P<0.05) and the anti-apoptotic protein Bcl-2 (P<0.01) while downregulating the pro-apoptotic proteins Bax (P<0.05) and Caspase-3 (P<0.01). Meanwhile, the Bcl-2/Bax ratio was significantly increased (P<0.05). Conclusion Butu decoction can improve ventricular remodeling and cardiac function in rats with heart failure, possibly by activating the AKT pathway, regulating Bcl-2/Bax proteins and inhibiting cardiomyocyte apoptosis.

Key words: Butu Decoction, Heart Failure, AKT Signaling Pathway, Bcl-2/Bax, Apoptosis, Cardiomyocyte, Rats

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