Volume 137, Issue 2 e70079
ORIGINAL ARTICLE

Huoxin Pill Ameliorates Atrial Fibrillation by Modulating Autonomic Nervous Balance and Electrical Conduction Heterogeneity: Insights From Systems Pharmacology and Experimental Validation

Mimi Huang

Mimi Huang

Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Contribution: ​Investigation, Visualization, Writing - original draft

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Lingli Wang

Lingli Wang

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou, People's Republic of China

Contribution: Methodology, Resources, Writing - original draft

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Zejun Xu

Zejun Xu

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou, People's Republic of China

Contribution: Resources

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Chenxing Huang

Chenxing Huang

Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Contribution: ​Investigation

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Sisi He

Sisi He

Innovation Research Institute of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Contribution: ​Investigation

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Yiqiu Liao

Yiqiu Liao

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou, People's Republic of China

Contribution: Resources

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Jiaxuan Li

Jiaxuan Li

Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Shandong Key Laboratory of Innovation and Application Research in Basic Theory of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Contribution: ​Investigation

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Fei Qin

Fei Qin

School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou Higher Education Mega Center, Guangzhou, People's Republic of China

Contribution: Resources

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Yongjun Chen

Yongjun Chen

Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Shandong Key Laboratory of Innovation and Application Research in Basic Theory of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Contribution: Writing - review & editing

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Qiqi Zhang

Qiqi Zhang

School of Acupuncture and Massage, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Contribution: Formal analysis

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Hongjun Yang

Corresponding Author

Hongjun Yang

Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China

Correspondence:

Hongjun Yang ([email protected])

Dongyan Liu ([email protected])

Taiyi Wang ([email protected])

Contribution: Resources, Writing - review & editing

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Dongyan Liu

Corresponding Author

Dongyan Liu

Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, People's Republic of China

Correspondence:

Hongjun Yang ([email protected])

Dongyan Liu ([email protected])

Taiyi Wang ([email protected])

Contribution: Resources, Supervision, Writing - review & editing

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Taiyi Wang

Corresponding Author

Taiyi Wang

Institute of Acupuncture and Moxibustion, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Shandong Key Laboratory of Innovation and Application Research in Basic Theory of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan, People's Republic of China

Correspondence:

Hongjun Yang ([email protected])

Dongyan Liu ([email protected])

Taiyi Wang ([email protected])

Contribution: Conceptualization, Funding acquisition, Resources, Supervision, Writing - review & editing

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First published: 22 July 2025

BCPT recognizes the potential of Natural Product studies in the identification of new therapies but wishes to emphasize that findings based on uncharacterized mixtures of compounds are preliminary in nature and serve primarily as hypothesis-generating to form the basis for more elaborate investigations.

Mimi Huang and Lingli Wang contributed equally to this work.

Funding: This work was supported by the Taishan Scholar Youth Project of Shandong Province (tsqn202306188 to TW) and the Young Scientists Fund of the National Natural Science Foundation of China (82404908 to DL).

ABSTRACT

Huoxin Pill (HXP), a traditional Chinese medicine for cardiovascular diseases, demonstrates clinically reported anti-atrial fibrillation (AF) effects, though its mechanisms remain unclear. To investigate these mechanisms, we established an acetylcholine-calcium chloride (ACh-CaCl2)-induced AF model in rats divided into control, AF, HXP (HXP-L: 3.33; HXP-M: 10; HXP-H: 30 mg/kg) and verapamil (25 mg/kg) groups. Following daily modelling, treatments were administered via gavage from Days 4 to 10. Electrocardiography (ECG) subsequently assessed AF susceptibility while echocardiography evaluated cardiac function. Systems pharmacology predicted HXP's targets/pathways for AF amelioration, with heart rate variability (HRV) and nerve activity recording examining autonomic balance. Electrical mapping quantified activation time (AT), conduction velocity (CV), conduction dispersion and effective refractory period (ERP) in isolated hearts. Results demonstrated that the AF group exhibited increased AF incidence/duration and decreased left ventricular ejection fraction/fractional shortening (LVEF/LVFS). Systems pharmacology revealed significant enrichment in cardiovascular pathways (including AF), while HRV and nerve recording indicated autonomic imbalance. Isolated AF hearts showed prolonged AT, slowed CV, increased conduction dispersion and shortened ERP. HXP significantly ameliorated these alterations. In conclusion, these findings suggest that HXP improves ACh-CaCl2-induced AF, potentially through modulating autonomic nervous balance and atrial electrical conduction heterogeneity.

Summary

  • This study investigated HXP, a traditional Chinese medicine, to understand how it prevents AF.
  • Experiments in AF-induced rats showed that HXP reduced the occurrence and duration of AF while improving heart function.
  • Systems pharmacology revealed that HXP is predominantly enriched in neuroinflammation and cardiac hypertrophy pathways. Additionally, HXP restored autonomic balance and stabilized irregular electrical signals in the heart.
  • These findings suggest HXP may offer a natural, multitarget approach to managing abnormal heart rhythms, supporting further exploration of traditional medicines for AF.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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