image: (a) The change of heart rate; (b) The change of LV+dp/dtmax; (c) The change of LV-dp/dtmax; (d) Serum levels of neuro-humoral factors (n = 8, *p < 0.05 vs. the KB group; #p < 0.05 and ##p < 0.01 vs. the M group). ALD, aldosterone; Ang-II, angiotensin II; ANP, atrial natriuretic peptide; BNP, brain natriuretic peptide; D, low-dose group; FWD, Fuzi water decoction; G, high-dose group; KB, blank group; LV+dp/dtmax, the maximal rising rate of left ventricle pressure; LV-dp/dtmax, the maximal declining rate of left ventricle pressure; M, model group; Y, positive group; Z, middle-dose group.
Credit: Cheng Peng, Jihai Gao, Jing Zhang, Dan Zhong
Background and objectives
Fuzi, the processed product of daughter roots of Aconitum carmichaelii Debx., is a well-known Chinese medicine for the treatment of heart failure (HF) and related cardiac diseases. This study aimed to investigate the molecular mechanism of the cardioprotective effects of Fuzi water decoction (FWD) and Fuzi water-soluble alkaloids (FWA) on the model of HF.
Methods
The HF model of rats was prepared through intravenous injection of propafenone hydrochloride. The normal group, model group, FWD-treated groups (1.25 g/kg, 2.5 g/kg, 5 g/kg) and positive group (Shenfu Injection, 3.3 mL/kg) were set up. Heart rate, LV+dp/dtmax, and LV-dp/dtmax were recorded at 5 m, 10 m, 20 m, 30 m, and 60 m after drug administration, respectively. The contents of atrial natriuretic peptide, brain natriuretic peptide (BNP), angiotensin II, and aldosterone in serum were determined 20 m post-administration. An in vitro cardiomyocyte hypertrophy model with HDAC2 overexpression was constructed and verified by lentivirus transfection. The experiment included a blank group, FWD-treated groups (3 mg/mL, 1.5 mg/mL), and FWA-treated groups (4 mg/mL, 2 mg/mL). For transcriptome analysis, the model group, blank group, and FWD-treated group (2.5 g/kg) at 20 m and 60 m in vivo, and different dose groups in vitro, were selected to analyze the therapeutic mechanisms of FWD and FWA.
Results
All FWD treatment groups showed an increased heart rate, among which the groups with 2.5 g/kg and 5 g/kg FWD showed better effects, significantly increasing LV+dp/dtmax and LV-dp/dtmax after 20 m of administration and significantly reducing BNP and aldosterone serum levels. In the constructed cardiomyocyte hypertrophy model, HDAC2 expression, atrial natriuretic peptide and BNP protein levels, and cell surface area increased. Transcriptome data from both in vivo and in vitro showed that FWD and FWA could exert cardioprotective effects through pathways such as the PI3K-Akt signaling pathway, NF-κB signaling pathway, and ATP-binding cassette (ABC) transporters, involving key genes such as ITGB1, TLR2, and CDKN1A. Fuzi inhibited the hypertrophic gene HDAC2. Additionally, based on weighted gene co-expression network analysis, ABC transporters may be an important molecular pathway for FWA in treating HF.
Conclusions
Both FWD and FWA can ameliorate HF by regulating apoptosis, proliferation, and anti-fibrosis, with ABC transporters potentially being the main pathway for the action of FWA.
Full text:
https://www.xiahepublishing.com/2835-6357/FIM-2024-00005
The study was recently published in the Future Integrative Medicine.
Future Integrative Medicine (FIM) publishes both basic and clinical research, including but not limited to randomized controlled trials, intervention studies, cohort studies, observational studies, qualitative and mixed method studies, animal studies, and systematic reviews.
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Journal
Future Integrative Medicine
Article Title
Transcriptomics-based Study on the Mechanism of Heart Failure Amelioration by Water Decoction and Water-soluble Alkaloids of Fuzi
Article Publication Date
25-Jun-2024