, Yuanyuan Li* 1
, Gaoran Xu 2
, Maochun Li 1
, Yingxiang Chen 3
, Li Xia 3
, Yiwei Ding 4
, Hankun Hu 5
, Yongji Lai 1
2Key Laboratory for Molecular Diagnosis of Hubei Province, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Thyroid and Breast Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
3Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
4Yicheng City People’s Hospital, Yicheng, China
5Department of Pharmacy, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China; Hubei Micro-explore Innovative Pharmaceutical Research Co., Ltd, Wuhan, China; Suzhou Organ-on-a-Chip System Science and Technology Co., Ltd, Suzhou, China
Abstract
Cardiac arrhythmias remain a leading cause of cardiovascular morbidity and mortality worldwide. Although conventional antiarrhythmic drugs are effective, their use is constrained by proarrhythmic risks and extracardiac toxicity. Wenxin Keli (WXKL), a traditional Chinese medicine (TCM) formula, has demonstrated antiarrhythmic properties in preclinical and clinical studies with a reportedly favorable safety profile. This article provides a critical synthesis of WXKL’s pharmacological mechanisms, including ion channel modulation (INa, ICaL, Ito), calcium handling, and calcium/calmodulin-dependent protein kinase II signaling, with explicit appraisal of translational limitations. Clinical trial evidence and meta-analyses for atrial fibrillation (AF), premature ventricular contractions, and other indications were systematically evaluated, with detailed discussion of effect sizes, heterogeneity, and methodological quality. Key challenges unique to WXKL as a TCM-derived product—formulation variability, quality control limitations, and regulatory approval pathways—are analyzed in depth. A prioritized research agenda is proposed to address evidence gaps.
*These authors contributed equally to this work and share first authorship.