Effects and Mechanisms of Wendan Decoction on Anxiety,Fear,and Insomnia in the Rat Model of Insomnia Due to Heart-Gallbladder Qi Deficiency

Runchen FANG, Songlin WANG, Hongsheng BIAN, Shuang YU, Yanyan WANG, Lili HUANG

Acta Academiae Medicinae Sinicae ›› 2025, Vol. 47 ›› Issue (6) : 863-872.

PDF(6459 KB)
Home Journals Acta Academiae Medicinae Sinicae
Acta Academiae Medicinae Sinicae

Abbreviation (ISO4): Acta Academiae Medicinae Sinicae      Editor in chief: Xuetao CAO

About  /  Aim & scope  /  Editorial board  /  Indexed  /  Contact  / 
PDF(6459 KB)
Acta Academiae Medicinae Sinicae ›› 2025, Vol. 47 ›› Issue (6) : 863-872. DOI: 10.3881/j.issn.1000-503X.16503
Original Articles

Effects and Mechanisms of Wendan Decoction on Anxiety,Fear,and Insomnia in the Rat Model of Insomnia Due to Heart-Gallbladder Qi Deficiency

Author information +
History +

Abstract

Objective To explore the effects and mechanisms of Wendan Decoction(WDT)on anxiety-like and fear-like behaviors,as well as sleep,in the rat model of insomnia due to heart-gallbladder qi deficiency. Methods SD male rats were randomly allocated into blank,model,Anshen Dingzhi pills(0.54 g/kg),low-,medium-,and high-dose(8.7,17.4,and 34.8 g/kg)WDT groups.Plantar electric stimulation combined with forced exercise was used for modeling,and the rats were administrated with corresponding agents by gavage for 7 consecutive days after the modeling.Behavioral tests were performed,and the c-Fos protein level,neuron firing rate,and hippocampal neurotransmitter content in brain regions were determined. Results Compared with the model group,medium-dose WDT shortened the avoidance time,freezing time,and sleep latency(P<0.001,P<0.001,P=0.010).Furthermore,medium-dose WDT attenuated the elevated c-Fos expression in emotion-related brain regions,including the prelimbic cortex(P<0.001),infralimbic cortex(P<0.001),basolateral amygdala(P<0.001),central amygdala(P<0.001),ventral hippocampus(P=0.004),periaqueductal gray(P<0.001),and dorsal raphe nucleus(P<0.001),as well as the increased firing rate of ventral hippocampal interneurons(P=0.005).In addition,it reduced the hippocampal glutamate content and the glutamate/gamma-aminobutyric acid ratio(P<0.001,P=0.013). Conclusions WDT can reduce the excitatory drive of glutamic acid to interneurons by inhibiting the release of glutamic acid from pyramidal neurons of ventral hippocampus,thus playing a role in improving sleep and mitigating the anxiety-like,fear-like,and depression-like behaviors in the rat model of insomnia due to heart-gallbladder qi deficiency.

Key words

Wendan Decoction / insomnia due to heart-gallbladder qi deficiency / ventral hippocampus / anxiety / fear

Cite this article

Download Citations
Runchen FANG , Songlin WANG , Hongsheng BIAN , et al . Effects and Mechanisms of Wendan Decoction on Anxiety,Fear,and Insomnia in the Rat Model of Insomnia Due to Heart-Gallbladder Qi Deficiency[J]. Acta Academiae Medicinae Sinicae. 2025, 47(6): 863-872 https://doi.org/10.3881/j.issn.1000-503X.16503

References

[1]
杨丹, 石岩, 王艺璇, 等. 睡眠剥夺引起机体损伤的分子机制及中药防治研究进展[J]. 中国中药杂志, 2023, 48(21):5707-5718.DOI:10.19540/j.cnki.cjcmm.20230710.703.
[2]
吴小薇. 常规针刺联合梅花针治疗心胆气虚型失眠的临床疗效研究[D]. 广州: 广州中医药大学, 2020.DOI:10.27044/d.cnki.ggzzu.2020.000356.
[3]
黄海阳. 温胆片治疗广泛性焦虑症的药效学实验研究与机制探讨[D]. 广州: 广州中医药大学, 2019.
[4]
胡莹, 李亮, 戴卫波, 等. 黄连温胆汤对氯苯丙氨酸致失眠小鼠的睡眠改善及γ-氨基丁酸能系统通路递质含量及受体表达的影响[J]. 中药新药与临床药理, 2022, 33(8):1009-1016.DOI:10.19378/j.issn.1003-9783.
[5]
关慧泉. 温胆汤合参芍片治疗失眠症临床研究[D]. 北京: 中国中医科学院, 2014.
[6]
Kim WB, Cho JH. Encoding of contextual fear memory in hippocampal-amygdala circuit[J]. Nat Commun, 2020, 11(1):1382.DOI:10.1038/s41467-020-15121-2.
[7]
Kim WB, Cho JH. Synaptic targeting of double-projecting ventral calhippocampal neurons to the medial prefrontal cortex and basal amygdala[J]. J Neurosci, 2017, 37(19):4868-4882.DOI:10.1523/JNEUROSCI.3579-16.2017.
[8]
Marrocco J, Mairesse J, Ngomba RT, et al. Anxiety-like behavior of prenatally stressed rats is associated with a selective reduction of glutamate release in the ventral hippocampus[J]. J Neurosci, 2012, 32(48):17143-17154.DOI:10.1523/jneurosci.1040-12.2012.
[9]
Silva J, Shao AS, Shen Y, et al. Modulation of hippocampal GABAergic neurotransmission and gephyrin levels by dihydromyricetin improves anxiety[J]. Front Pharmacol, 2020, 11:1008.DOI:10.3389/fphar.2020.01008.
[10]
Schiel JE, Holub F, Petri R, et al. Affect and arousal in insomnia:through a lens of neuroimaging studies[J]. Curr Psychiatry Rep, 2020, 22(9):44.DOI:10.1007/s11920-020-01173-0.
[11]
Spiegelhalder K, Regen W, Baglioni C, et al. Neuroimaging studies in insomnia[J]. Curr Psychiatry Rep, 2013, 15(11):405.DOI:10.1007/s11920-013-0405-0.
[12]
Graeff FG, Netto CF, Zangrossi H, et al. The elevated t-maze as an experimental model of anxiety[J]. Neurosci Biobehav Rev, 1998, 23(2):237-246.DOI:10.1016/s0149-7634(98)00024-4.
[13]
Huang L, Lv X, Ze X, et al. Combined probiotics attenuate chronic unpredictable mild stress-induced depressive-like and anxiety-like behaviors in rats[J]. Front Psychiatry, 2022, 13:990465.DOI:10.3389/fpsyt.2022.990465.
[14]
马剑飞. 十味温胆汤治疗心胆气虚证不寐临床观察[J]. 光明中医, 2022, 37(6):947-949.
[15]
李亮, 王珠强, 胡莹, 等. 基于神经递质和5-HT1A/Gαi/o/cAMP信号通路研究黄连温胆汤对失眠大鼠的治疗作用及机制[J]. 中药新药与临床药理, 2023, 34(5):591-598.DOI:10.19378/j.issn.1003-9783.
[16]
Jimenez JC, Su K, Goldberg AR, et al. Anxiety cells in a hippocampal-hypothalamic circuit[J]. Neuron, 2018, 97(3):670-683.e6.DOI:10.1016/j.neuron.2018.01.016.
[17]
Sotres-Bayon F, Sierra-Mercado D, Pardilla-Delgado E, et al. Gating of fear in prelimbic cortex by hippocampal and amygdala inputs[J]. Neuron, 2012, 76(4):804-812.DOI:10.1016/j.neuron.2012.09.028.
[18]
邝慧. 海马CA1区锥体神经元和多种中间神经元在情景事件编码中的作用[D]. 上海: 华东师范大学, 2011.
[19]
Tzilivaki A, Tukker JJ, Maier N, et al. Hippocampal GABAergic interneurons and memory[J]. Neuron, 2023, 111(20):3154-3175.DOI:10.1016/j.neuron.2023.06.016.
[20]
Udakis M, Pedrosa V, Chamberlain SEL, et al. Interneuron-specific plasticity at parvalbumin and somatostatin inhibitory synapses onto CA1 pyramidal neurons shapes hippocampal output[J]. Nat Commun, 2020, 11(1):4395.DOI:10.1038/s41467-020-18074-8.
[21]
Linley SB, Vertes RP. Serotonergic systems in sleep and waking[M]// Dringenberg HC.Handbook of behavioral neuroscience. London: Academic Press, 2019:101-123.
[22]
Hung C, Yamanaka A. The role of orexin neuron activity in sleep/wakefulness regulation[J]. Peptides, 2023, 165:171007.DOI:10.1016/j.peptides.2023.171007.
[23]
De Luca R, Nardone S, Grace KP, et al. Orexin neurons inhibit sleep to promote arousal[J]. Nat Commun, 2022, 13(1):4163.DOI:10.1038/s41467-022-31591-y.
[24]
Wang Y, Liu N, Ma L, et al. Ventral hippocampal ca1 pyramidal neuronsencode nociceptive information[J]. Neurosci Bull, 2024, 40(2):201-217.DOI:10.1007/s12264-023-01086-x.
[25]
Volitaki E, Forro T, Li K, et al. Activity of ventral hippocampal parvalbumin interneurons during anxiety[J]. Cell Rep, 2024, 43(6):114295.DOI:10.1016/j.celrep.2024.114295.
[26]
Singewald N, Schmuckermair C, Whittle N, et al. Pharmacology of cognitive enhancers for exposure-based therapy of fear,anxiety and trauma-related disorders[J]. Pharmacol Ther, 2015, 149:150-190.DOI:10.1016/j.pharmthera.2014.12.004.
PDF(6459 KB)

Accesses

Citation

Detail

Sections
Recommended

/