小檗碱调控心房颤动相关心房重构的多维机制——从炎症免疫、代谢重编程到离子通道重塑
Multidimensional Mechanisms of Berberine in Regulating Atrial Fibrillation-Related Atrial Remodeling—From Inflammation and Immunity, Metabolic Reprogramming to Ion Channel Remodeling
DOI: 10.12677/hjbm.2026.164069, PDF,   
作者: 宗光达, 郭智杰：内蒙古医科大学鄂尔多斯临床医学院，内蒙古 鄂尔多斯；王海军*：内蒙古医科大学鄂尔多斯临床医学院，内蒙古 鄂尔多斯；鄂尔多斯市中心医院心血管内科，内蒙古 鄂尔多斯
关键词: 小檗碱；心房颤动；心房重构；炎症免疫；代谢重编程；Berberine； Atrial Fibrillation； Atrial Remodeling； Inflammation and Immunity； Metabolic Reprogramming
摘要: 心房颤动(atrial fibrillation, AF)是临床最常见的心律失常之一，其病理基础涉及心房结构、电生理及代谢的复杂重构。小檗碱作为天然异喹啉类生物碱，近年研究揭示其可通过多靶点、多通路调控心房重构，具有潜在抗AF作用。然而，现有研究多聚焦于单一机制，缺乏对小檗碱多维调控作用的系统整合。本文旨在系统综述小檗碱在AF相关心房重构中的调控机制，重点从炎症免疫反应、代谢重编程、离子通道重塑及心房纤维化/结构重构等维度展开：通过抑制核因子κB (nuclear factor-κB, NF-κB)及含NLR家族Pyrin结构域蛋白3 (NLR family pyrin domain containing 3, NLRP3)炎症小体信号通路减轻炎症反应；通过激活腺苷酸活化蛋白激酶(adenosine monophosphate-activated protein kinase, AMPK)相关通路纠正能量代谢紊乱；通过调节钙、钾、钠通道及缝隙连接改善电生理异常；并通过抑制成纤维细胞活化、氧化应激和内质网应激减轻结构重构。本文还探讨了小檗碱临床转化的挑战与前景，为AF的精准治疗提供理论依据。
Abstract: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias encountered in clinical practice, and its pathological basis involves complex remodeling of atrial structure, electrophysiology, and metabolism. Berberine, a natural isoquinoline alkaloid, has recently been shown to regulate atrial remodeling through multiple targets and pathways, suggesting its potential anti-AF effects. However, existing studies have mainly focused on individual mechanisms, and a systematic integration of the multidimensional regulatory effects of berberine remains lacking. This review aims to systematically summarize the regulatory mechanisms of berberine in AF-related atrial remodeling, with a focus on inflammation and immune responses, metabolic reprogramming, ion-channel remodeling, and atrial fibrosis/structural remodeling. Specifically, berberine may attenuate inflammatory responses by inhibiting nuclear factor-κB (NF-κB) and NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathways; correct energy metabolic disturbances by activating adenosine monophosphate-activated protein kinase (AMPK)-related pathways; improve electrophysiological abnormalities by modulating calcium, potassium, and sodium channels as well as gap junctions; and alleviate structural remodeling by inhibiting fibroblast activation, oxidative stress, and endoplasmic reticulum stress. This review also discusses the challenges and prospects of the clinical translation of berberine, providing a theoretical basis for precision therapy in AF.
文章引用：宗光达, 郭智杰, 王海军. 小檗碱调控心房颤动相关心房重构的多维机制——从炎症免疫、代谢重编程到离子通道重塑[J]. 生物医学, 2026, 16(4): 675-685. https://doi.org/10.12677/hjbm.2026.164069

参考文献

[1] Brundel, B.J.J.M., Ai, X., Hills, M.T., Kuipers, M.F., Lip, G.Y.H. and de Groot, N.M.S. (2022) Atrial Fibrillation. Nature Reviews Disease Primers, 8, Article No. 21. [Google Scholar] [CrossRef] [PubMed]
[2] Sridhar, A., DeSantiago, J., Chen, H., Pavel, M.A., Ly, O., Owais, A., et al. (2024) Modulation of NOX2 Causes Obesity-Mediated Atrial Fibrillation. Journal of Clinical Investigation, 134, e175447. [Google Scholar] [CrossRef] [PubMed]
[3] Zhao, N., Li, Q., Zhang, K., Wang, K., He, R., Yuan, Y., et al. (2020) Heart Failure-Induced Atrial Remodelling Promotes Electrical and Conduction Alternans. PLOS Computational Biology, 16, e1008048. [Google Scholar] [CrossRef] [PubMed]
[4] Spinelli, V., Laurino, A., Balducci, V., Gencarelli, M., Ruzzolini, J., Nediani, C., et al. (2024) Interleukin-6 Modulates the Expression and Function of HCN Channels: A Link between Inflammation and Atrial Electrogenesis. International Journal of Molecular Sciences, 25, Article 12212. [Google Scholar] [CrossRef] [PubMed]
[5] Haugaard, S.L., Nissen, S.D., Schneider, M.J., Birk, J.B., Carstensen, H., Hopster-Iversen, C., et al. (2025) The Horse Cardiac Transcriptome: Moving Towards a Molecular Understanding of Atrial Fibrillation. Equine Veterinary Journal. [Google Scholar] [CrossRef] 
[6] Ju, H., Liu, T., Yang, M., Cheng, M. and Wu, G. (2023) Iron and Atrial Fibrillation: A Review. Pacing and Clinical Electrophysiology, 46, 312-318. [Google Scholar] [CrossRef] [PubMed]
[7] Wang, G., He, Q., Shuai, W., Yang, H., Kong, B., Lu, S., et al. (2025) The Gut Microbial Metabolite Phenylacetylglutamine Increases Susceptibility to Atrial Fibrillation after Myocardial Infarction through Ferroptosis and NLRP3 Inflammasome. Apoptosis, 30, 210-225. [Google Scholar] [CrossRef] [PubMed]
[8] Zhang, H., Shan, Y., Wu, Y., Xu, C., Yu, X., Zhao, J., et al. (2017) Berberine Suppresses LPS-Induced Inflammation through Modulating Sirt1/NF-κB Signaling Pathway in RAW264.7 Cells. International Immunopharmacology, 52, 93-100. [Google Scholar] [CrossRef] [PubMed]
[9] Zhang, M., Wang, S.J., Du, X.Q., Li, G.A., et al. (2026) Decoding the Healing Secrets of Gegenqinlian Decoction: A Promising Approach to Radiation-Induced Intestinal Injury. Journal of Ethnopharmacology, 354, Article 120473. [Google Scholar] [CrossRef] 
[10] Guo, T., Liu, Z., Chang, L., Jiang, J., Lu, M., Fan, Y., et al. (2025) Holistic Modulation of TLR4, MAPK, and Apoptosis Signalings and Gut Microbiota by Sihuangzhili Granule: A Herbal Strategy against Avian Colibacillosis. Poultry Science, 104, Article 106032. [Google Scholar] [CrossRef] 
[11] Zhang, J., Wang, Y., Jiang, H., Tao, D., Zhao, K., Yin, Z., et al. (2022) Preventive Effect of Berberine on Postoperative Atrial Fibrillation. Circulation: Arrhythmia and Electrophysiology, 15, e011160. [Google Scholar] [CrossRef] [PubMed]
[12] Zhou, Z., Xu, Y., Xiao, X., Huang, T., Zhao, J., Huang, Y., et al. (2026) Berberine Inhibits NLRP3 Inflammasome Activation by Upregulating the SIRT6-AMPK Pathway to Prevent Angiotensin II-Induced Fibrosis and Vulnerability to Atrial Fibrillation. International Immunopharmacology, 168, Article 115919. [Google Scholar] [CrossRef] 
[13] An, N., Yang, F., Liu, N., Gao, Y., Shang, H. and Xing, Y. (2025) Berberine Ameliorates Atrial Remodeling and Inhibits the Atrial Fibrillation of Mice via Regulating NLRP3 Inflammasome. Phytotherapy Research, 39, 3998-4010. [Google Scholar] [CrossRef] [PubMed]
[14] DiNicolantonio, J.J., McCarty, M.F. and O’Keefe, J.H. (2022) Nutraceutical Activation of Sirt1: A Review. Open Heart, 9, e002171. [Google Scholar] [CrossRef] [PubMed]
[15] Cao, Z., Duan, J., Meng, S., Zhou, Z., Huang, Y., Chen, X., et al. (2026) Berberine Reduces Atrial Lipotoxicity and Endoplasmic Reticulum Stress to Alleviate Heart Failure with Preserved Ejection Fraction (HFpEF)-Associated Atrial Fibrillation via AMPK Signaling. Phytotherapy Research, 40, 1195-1216. [Google Scholar] [CrossRef] 
[16] Xiong, K., Deng, J., Yue, T., Hu, W., Zeng, X., Yang, T., et al. (2023) Berberine Promotes M2 Macrophage Polarisation through the IL-4-STAT6 Signalling Pathway in Ulcerative Colitis Treatment. Heliyon, 9, e14176. [Google Scholar] [CrossRef] [PubMed]
[17] Qi, Y., Zhao, X., Wu, W., Wang, N., Ge, P., Guo, S., et al. (2025) Coptisine Improves LPS-Induced Anxiety-Like Behaviors by Regulating the Warburg Effect in Microglia via PKM2. Biomedicine & Pharmacotherapy, 183, Article 117837. [Google Scholar] [CrossRef] [PubMed]
[18] Huang, J., Lu, J., Wu, C., Chen, S., Chang, T., Xu, L., et al. (2025) Berberine Hydrochloride Reduces the Intracellular Survival of Salmonella Typhimurium by Enhancing Host Autophagic Flux through the Inhibition of the Type III Secretion System. Biomolecules, 15, Article 1589. [Google Scholar] [CrossRef] 
[19] Yanru, Y., Jia, C. and Yan, Y. (2025) Berberine in Diabetic Nephropathy: Mechanistic Overview. Diabetology International, 17, Article No. 9. [Google Scholar] [CrossRef] 
[20] Wang, Y., Sun, Z., Yin, Z., Zhang, J., Xin, F., Xu, Y., et al. (2025) Berberine Improves Atrial Remodeling by Regulating the AMPK/PPARα Signaling Pathway in a Rabbit Model of Atrial Fibrillation. Journal of Applied Biomedicine, 23, 63-79. [Google Scholar] [CrossRef] [PubMed]
[21] Tao, J., Hao, T.C., Zhang, X.Y., Lu, P. and Yang, Y. (2025) Coptisine Inhibits Lipid Accumulation in High Glucose-and Palmitic Acid-Induced HK-2 Cells by Regulating the AMPK/ACC/CPT-1 Signaling Pathway. Naunyn-Schmiedeberg’s Archives of Pharmacology, 398, 5465-5474. [Google Scholar] [CrossRef] [PubMed]
[22] Hori, I., Harashima, H. and Yamada, Y. (2023) Development of a Mitochondrial Targeting Lipid Nanoparticle Encapsulating Berberine. International Journal of Molecular Sciences, 24, Article 903. [Google Scholar] [CrossRef] [PubMed]
[23] Wang, H., Gao, Y., Ma, P., Jiang, X., Wang, Z., Tang, Y., et al. (2025) Jiao-Tai-Wan and Its Component Coptisine Attenuate PCOS by Regulating Mitochondrial Cholesterol Import through Suppression of SIRT1 Ubiquitination. Phytomedicine, 148, Article 157446. [Google Scholar] [CrossRef] 
[24] Yang, K.T., Chao, T.H., Wang, I.C., Luo, Y.P., et al. (2022) Berberine Protects Cardiac Cells against Ferroptosis. Tzu Chi Medical Journal, 34, 310-317. [Google Scholar] [CrossRef] [PubMed]
[25] Huang, X., Wang, C., Wang, Y., Yang, S., Du, L., Li, L., et al. (2026) The Mechanism of Electrical Remodeling in Atrial Fibrillation and Current Research Status of Natural Drugs and Active Ingredients Inhibiting Atrial Electrical Remodeling. Frontiers in Cardiovascular Medicine, 13, Article 1705565. [Google Scholar] [CrossRef] 
[26] Masoumi, S., Moetazedian, M., Jafari, S., Heidari-Soureshjani, S. and Sherwin, C.M. (2025) Mechanistic Effects and Complications of Berberine on Cardiac Arrhythmias: A Systematic Review. Current Reviews in Clinical and Experimental Pharmacology, 21, 117-132. [Google Scholar] [CrossRef] [PubMed]
[27] Liu, X., Liang, Q., Wang, Y., Xiong, S. and Yue, R. (2024) Advances in the Pharmacological Mechanisms of Berberine in the Treatment of Fibrosis. Frontiers in Pharmacology, 15, Article 1455058. [Google Scholar] [CrossRef] [PubMed]
[28] An, N., Zhang, G., Li, Y., Yuan, C., Yang, F., Zhang, L., et al. (2022) Promising Antioxidative Effect of Berberine in Cardiovascular Diseases. Frontiers in Pharmacology, 13, Article 865353. [Google Scholar] [CrossRef] [PubMed]
[29] Ai, X., Yu, P., Peng, L., Luo, L., Liu, J., Li, S., et al. (2021) Berberine: A Review of Its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases. Frontiers in Pharmacology, 12, Article 762654. [Google Scholar] [CrossRef] [PubMed]
[30] Vanti, G., Coronnello, M., Bani, D., Mannini, A., Bergonzi, M.C. and Bilia, A.R. (2021) Co-Delivery of Berberine Chloride and Tariquidar in Nanoliposomes Enhanced Intracellular Berberine Chloride in a Doxorubicin-Resistant K562 Cell Line Due to P-GP Overexpression. Pharmaceutics, 13, Article 306. [Google Scholar] [CrossRef] [PubMed]
[31] Salek, A., Selmi, M., Barboura, M., Martinez, M.C., Chekir-Ghedira, L. and Andriantsitohaina, R. (2022) Enhancement of the in Vitro Antitumor Effects of Berberine Chloride When Encapsulated within Small Extracellular Vesicles. Pharmaceutics, 14, Article 1913. [Google Scholar] [CrossRef] [PubMed]
[32] Yang, D., Cao, J., Jiao, L., Yang, S., Zhang, L., Lu, Y., et al. (2020) Solubility and Stability Advantages of a New Cocrystal of Berberine Chloride with Fumaric Acid. ACS Omega, 5, 8283-8292. [Google Scholar] [CrossRef] [PubMed]
[33] Liu, Z.B., Lu, Q., Liu, J. and Ding, S.F. (2025) Combination of Colchicine and Berberine for Reducing Atrial Fibrillation Recurrence Post-Ablation and Preventing Postoperative Atrial Fibrillation: A Promising Approach? International Journal of Cardiology, 435, Article 133393. [Google Scholar] [CrossRef] [PubMed]
[34] Harrison, S.A., Gunn, N., Neff, G.W., Kohli, A., Liu, L., Flyer, A., et al. (2021) A Phase 2, Proof of Concept, Randomised Controlled Trial of Berberine Ursodeoxycholate in Patients with Presumed Non-Alcoholic Steatohepatitis and Type 2 Diabetes. Nature Communications, 12, Article No. 5503. [Google Scholar] [CrossRef] [PubMed]

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