Exploring the Anti-Epileptic Mechanism of Chaihu Longgu Muli Decoction from the Perspective of “The Heart and Gallbladder Have a Separate Connection”
DOI:
https://doi.org/10.53469/wjimt.2025.08(09).08Keywords:
The Heart and Gallbladder Have a Separate Connection, Epilepsy, Chaihu Longgu Muli Decoction, Phlegm-fire disturbing the heart, Bile acid metabolism, NeuroinflammationAbstract
Epilepsy is a chronic central nervous system disorder characterized by abnormal synchronous neuronal discharges, posing a serious threat to global public health. The classic Chinese medicine formula Chaihu Longgu Muli Decoction has demonstrated significant anti-epileptic efficacy in clinical practice. Guided by the TCM theory that “The Heart and Gallbladder Have a Separate Connection,” and incorporating the principles of meridian interconnectivity and Qi transformation, this study analyzes the core pathogenesis of epilepsy as “dysfunction of the Gallbladder Pivot leading to Qi stagnation, phlegm, and fire, which ascend to disturb the Heart Spirit.” Modern medical research supports this theory, confirming that bile acid metabolism disorders and neuroinflammatory responses are common in epilepsy patients. Through a systematic analysis of the composition and compatibility of Chaihu Longgu Muli Decoction, this article reveals its triple mechanism of action: “unblocking and facilitating the Gallbladder Pivot,” “clearing and transforming phlegm-fire,” and “restoring the ascending and descending movement of Qi.” This multi-target, multi-level approach enables systematic intervention in the complex pathological network of epilepsy. This study not only offers innovative insights into TCM treatment of epilepsy from the unique perspective of “The Heart and Gallbladder Have a Separate Connection,” but also highlights the systemic advantages of TCM formulas in holistic regulation and multi-target intervention. Furthermore, it provides important theoretical foundations and new research directions for clinical application, integrative medicine approaches, and TCM treatment of complex neurological disorders.
References
Asadi-Pooya A A, Brigo F, Lattanzi S, et al. Adult epilepsy[J]. Lancet,2023,402: 412-424.
Ding D, Zhou D, Sander JW, et al. Epilepsy in China: major progress in the past two decades[J]. Lancet Neurol,2021,20:316-326.
Shakhatreh L, Foster E, Siriratnam P, et al. Impact of epilepsy surgery on quality of life: systematic review and meta- analysis[J]. Epilepsia, 2023, 64(7): 1709- 1721.
Tashakori- miyanroudi M, Souresrafil A, Hashemi P, et al. Prevalence of depression, anxiety, and psychological distress in patients with epilepsy during Covid-19: a systematic review[J]. Epilepsy Behav, 2021, 125:108410.
Moshé S L, Perucca E, Ryvlin P, et al. Epilepsy: new advances [J]. Lancet (London, England), 2015, 385(9971): 884-98.
Jin Liang, Chen Yujie, Chen Yongjun. Research progress on the genetic etiology and diagnosis and treatment of developmental and epileptic encephalopathy[J]. Heredity, 2023, 45(07): 553-567.
Chen TS, Huang TH, Lai MC, et al. The Role of Glutamate Receptors in Epilepsy[J]. Biomedicines, 2023, 11(3): 783.
Daniela Zizioli, Simona Bernardi, Marco Varinelli, et al. Development of BCR-ABL1 transgenic zebrafish model reproducing chronic myeloid leukemia (CML) like-disease and providing a new insight into CML mechanisms[J]. Cells (Basel, Switzerland), 2021,10(2):445.
Löscher W, Potschka H, Sisodiya S M, et al. Drug resistance in epilepsy: clinical impact, potential mechanisms, and new innovative treatment options[J]. Pharmacol Rev, 2020, 72(3): 606-638.
Victor T R, Tsirka S E. Microglial contributions to aberrant neurogenesis and pathophysiology of epilepsy[J]. Neuroimmunol Neuroinflamm, 2020, 7: 234-247.
Löscher W, Friedman A. Structural, molecular, and function alalterations of the blood-brain barrier during epileptogenesis and epilepsy: a cause, consequence, or both? [J]. Int J Mol Sci, 2020, 21(2): 591.
Wang Yixi, Huang Baiwei. Research progress on epilepsy-related induction mechanisms and treatment methods[J]. Chinese Journal of Practical Neurological Diseases, 2024, 27(09): 1168-1172.
Lukawski K, Czuczwar S J. Oxidative stress and neurodegeneration in animal models of seizures and epilepsy [J]. Antioxidants (Basel),2023, 12(5):1049. D0I:10.3390/antiox12051049.
Li Yu, Shangguan Yafei. Research progress and clinical application of immunotherapy in the treatment of epilepsy[J]. Journal of Epilepsy and Neuroelectrophysiology, 2025, 34(02): 110-114. DOI: 10.19984/ j.cnki.1674-8972.2025.02.09.
Olson C A, Vuong H E, Yano J M, et al. The gut microbiota mediates the anti- seizure effects of the ketogenic diet[J]. Cell,2018,173(7):1728- 1741.
Siarava E, Hyphantis T, Pelidou S H, et al. Factors related to the adverse events of antiepileptic drugs[J]. Epilepsy Behav, 2020, 111: 107199.
Wang Kaiyue, Sun Tianye, Wang Yue, et al. Exploring the pathogenesis of epilepsy from the perspective of the correlation between the theory of “clear and turbid coherence” and ferroptosis[J]. Journal of Traditional Chinese Medicine, 2024, 39(06): 1177-1181.
Huang Qin, Sui Lisen, Xie Haitao, et al. On the guiding significance of the “poison-channel-viscera” theory for the diagnosis and treatment of epilepsy[J]. Chinese Journal of Emergency Medicine, 2017, 26(09): 1572-1575.
Li Chen. Introduction to Medicine[M]. Beijing: China Traditional Chinese Medicine Press, 1995:72
Zong Xueyu, Wang Shuai, Chi Lili. Treatment of chronic cholecystitis with anxiety and depression based on the theory of heart-gallbladder communication[J]. Shandong Journal of Traditional Chinese Medicine, 2022, 41(03): 255-258.
Li Zhiyong. Zhang Jingyue's Complete Medical Works[M]. Beijing: China Traditional Chinese Medicine Press, 2015.
Sui Dynasty. Chao Yuanfang. Treatise on the Origin and Symptoms of Various Diseases[M]. Beijing: China Medical Science and Technology Press, 2011:95.
Wang Yaqi, Dong Hong, Cui Yumiao, et al. Analysis of the diagnosis and treatment of refractory epilepsy from the perspective of Shaoyang phlegm and blood stasis[J]. Traditional Chinese Medicine Forum, 2024, 39(06): 1-4.
Zhang H Y, Wang Y, He Y, et al. A1 astrocytes contribute to murine depression-like behavior and cognitive dysfunction, which can be alleviated by IL-10 or fluorocitrate treatment[J]. J Neuroinflammation, 2020, 17(1):200.
Pearson-smith J N, Patel M. Metabolic dysfunction and oxidative stress in epilepsy[J]. Int J Mol Sci,2017, 18(11):2365.
Guzior D V, Quinn R A. Review: Microbial transformations of human bile acids[J]. Microbiome, 2021, 9(1): 140.
Gu X, Yuan L, Gan L, et al. Understanding the Role of Exercise and Probiotic Interventions on Non-Alcoholic Fatty Liver Disease Alleviation in Zebrafish: Dialogue Between the Gut and Liver[J]. Int J Mol Sci. 2025;26(3):1360.
Zhou X, Hollern D, Liao J, et al. NMDA receptor-mediated excitotoxicity depends on the coactivation of synaptic and extrasynapticreceptors [J]. Cell death & disease, 2013, 4(3): e560-e560.
Gulcebi M, Akman O, Carcak N, et al. Evaluation of GAD67 immunoreactivity in the region of substantia nigra pars reticulata in resistance to development of convulsive seizure in genetic absence epilepsy rats[J]. North Clin Istanb, 2017, 3(3):161-167.
Akyuz E, Polat AK, Eroglu E, et al. Revisiting the role of neurotransmitters in epilepsy:an updated review[J]. Life Sci,2021, 265:118826.
Wang Y K, Li J, Wu L, et al. Saikosaponins regulate bile acid excretion in mice liver and ileum by activating farnesoid X receptor and bile acid transporter[J]. Phytother Res, 2023, 37(10): 4572-4586.
Wang Aiting, Miao Zenghui, Zhang Ying, et al. Study on the mechanism of baicalin in alleviating metformin-induced early diarrhea in mice by regulating microbiota-bile acid-intestinal barrier[J]. Acta Pharmaceutical Sinica, 2025, 60(07): 2246-2253.
Li C, Li B, Liu H, et al. Mechanism of Chaihu Longgu oyster adjusted decoction for the treatment of depression based on network pharmacology and molecular docking technology. Ann Transl Med,2023, 11(4):172.
Yan Deqi, Zhang Xingping, Liang Zhengting, et al. Sedative mechanism of Guizhi Jia Longgu Muli Decoction on anxiety-like behavior in rats with insomnia caused by Po Anrest in the Lungs[J]. Chinese Journal of Traditional Chinese Medicine, 2024, 39(03): 1468-1475.
Yang Feihong, Lin Chao, Sun Xiangyu, et al. Ginsenoside Rb1 improves hypoxic-ischemic brain damage in neonatal mice through the ERK pathway[J]. Journal of Neuroanatomy, 2025, 41(03): 261-271.
Xie Zhe, Shi Yifan, Su Linzhe, et al. Research progress on the treatment of depression with Pinellia ternata and its prescription compatibility [J/OL]. Chinese Journal of Experimental Traditional Chinese Medicine, 1-21 [2025-08-19].
Xu Yongjie, Jia Xiaolong, Wang Yanling. Effect of Pachycolic Acid on Brain Tissue Damage in Rats with Cerebral Hemorrhage by Regulating cAMP/PKA/CREB Signaling Pathway[J]. Anhui Medical Journal, 2025, 29(05): 898-902+1061.
Ji C L, Deng Y S, Yang A C, et al. Rhubarb enema improved colon mucosal barrier injury in 5/6 nephrectomy rats may associate with gut microbiota modification[J]. Front Pharmacol, 2020, 11:1092.
Wang Weichen, Ma Yaping, Wang Meng, et al. Exploring the therapeutic effect of emodin on mice with cholestatic liver injury based on the CYP7A1/FXR/SHP pathway [J/OL]. Chinese Journal of Clinical Pharmacology and Therapeutics, 1-10 [2025-08-19].
Yan Wenting. Clinical study on modified Chaihu Guizhi Longmu decoction combined with flupentixol and melitracen in the treatment of anxiety-related insomnia[J]. Practical Clinical Integration of Traditional Chinese and Western Medicine, 2023, 23(11):60-63.
Shan Ping, Zhang Jilong. Effects and mechanisms of Chaihu Jia Longgu Muli Decoction on neuronal damage in rats with refractory epilepsy[J]. Chinese Pharmacy, 2025, 36(06): 692-697.
Han Hui, Zhang Keyi, Wang Ying, et al. Exploring the intervention mechanism of Bupleurum Longgu Muli Decoction on energy metabolism in epileptic rats based on AMPK/Nrf2 signaling pathway[J]. Sichuan Journal of Traditional Chinese Medicine, 2025, 43(04): 143-148.
Yizhi M A O, Liang L, Zhihong L, et al. Chaihu Longgu Muli Decoction relieving temporal lobe epilepsy in rats by inhibiting TLR4 signaling pathway through miR-146a-3p and miR-146a-5p[J]. Digital Chinese Medicine, 2022, 5(3): 317-325.
Zhu Yong, Li Liang, Wu Huaying, et al. Exploration of the mechanism of action of Chaihu Longgu Muli Decoction in treating epilepsy based on network pharmacology[J]. Journal of Hunan University of Traditional Chinese Medicine, 2019, 39(10): 1212-1217.
Wang Xin, Zhang Xiaoqian, Yan Limei, et al. Effect of Chaihu Jia Longgu Muli Decoction on glial fibrillary acidic protein, neuropeptide Y and S100B in patients with epilepsy based on the brain-gut axis theory[J]. Liaoning Journal of Traditional Chinese Medicine, 2023, 50(1): 1-5.