The AB-PL herb pair significantly reduced systolic/diastolic blood pressure, cardiac hypertrophy markers, natriuretic peptides, and improved left ventricular ejection fraction compared to hypertensive mice treated with L-NAME alone.
Does the herb pair Achyranthes bidentata and Paeonia lactiflora Pall. (AB-PL) improve cardiac function and reduce blood pressure in a mouse model of hypertensive cardiomyopathy?
The herb pair AB-PL ameliorates hypertensive cardiomyopathy in mice by modulating nitrogen metabolism, oxidative stress, and inflammation, providing a potential mechanistic basis for its clinical use.
Effect estimate: SBP, DBP, MAP significantly reduced by AB-PL vs. L-NAME model (p<0.05); HW/BW and HW/TL ratios significantly decreased (p<0.01); ANP and BNP levels significantly reduced (p<0.05); LVEF significantly improved (p<0.05)
p-value: p=<0.05, <0.01 for key endpoints
The herb pair Achyranthes bidentata Blume and Paeonia lactiflora Pall. (AB-PL) has demonstrated significant efficacy in the treatment of hypertensive cardiomyopathy; however, its underlying mechanisms remain unclear. In this study, we established an integrated framework combining predictive network pharmacology and experimental exploration to investigate the action mechanisms of AB-PL. The potential antihypertensive targets and pathways of AB-PL were predicted via network pharmacology analysis. These predictions were further explored and assessed in a hypertensive C57 mouse model using real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, immunohistochemistry, metabolomics, and other assays. The network pharmacology analysis suggested that the active components of AB-PL (e.g., paeoniflorin) may alleviate hypertensive cardiomyopathy by modulating nitrogen metabolism, oxidative stress, inflammation, and the lipid metabolic pathways. Our experimental results show that AB-PL significantly reduces blood pressure and decreases the levels of atrial and brain natriuretic peptides while improving left ventricular ejection fraction in hypertensive mice. AB-PL treatment also ameliorates abnormalities in the nitrogen metabolism biomarkers. Fluorescent probe detection, RT-qPCR, and immunohistochemical analyses indicate that AB-PL significantly alters the expression levels of reactive oxygen species, superoxide dismutase, Keap1, Nrf2, and HO-1. In addition, AB-PL suppresses inflammatory responses by inhibiting the expression of NLRP3, ASC, gasdermin D, IL-1β, and IL-18. Metabolomic analysis further suggested the regulatory effects of AB-PL on the lipid metabolism pathways, including fatty acid biosynthesis. In conclusion, this study provides insights into the potential antihypertensive cardiomyopathic mechanisms of AB-PL through a combined bioinformatic and experimental approach, which support its potential clinical application for the prevention and treatment of hypertensive cardiomyopathy.
Zhang et al. (Wed,) conducted a other in Male hypertensive C57BL/6 mice induced with L-NAME (n=45). Achyranthes bidentata and Paeonia lactiflora Pall. herb pair (AB-PL) vs. Model group (L-NAME alone) and positive control (L-NAME + fosinopril 20 mg/kg/d) was evaluated on Change in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), cardiac hypertrophy (HW/BW and HW/TL ratios), natriuretic peptides (ANP, BNP), and left ventricular ejection fraction (LVEF) (SBP, DBP, MAP significantly reduced by AB-PL vs. L-NAME model (p<0.05); HW/BW and HW/TL ratios significantly decreased (p<0.01); ANP and BNP levels significantly reduced (p<0.05); LVEF significantly improved (p<0.05), p=<0.05, <0.01 for key endpoints). The AB-PL herb pair significantly reduced systolic/diastolic blood pressure, cardiac hypertrophy markers, natriuretic peptides, and improved left ventricular ejection fraction compared to hypertensive mice treated with L-NAME alone.