Antidepressant Effects and Mechanism of Dingzhixiaowan and Kaixinwan on CUMS Model Rats

doi:10.19803/j.1672-8629.2021.12.08

Abstract

Abstract: Objective To compare the effect of Dingzhixiaowan pills recorded in Essential Recipes for Emergent Use Worth One Thousand and Kaixinwan pills recored in Yimenfang on chronic unpredictable mild stress (CUMS) depression model rats and its possible mechanism.Methods A CUMS rat model was established. The rats were randomly divided into the normal group, model group, Dingzhixiaowan group, and Kaixinwan group. The rats in the last two groups were given their respective drug intragastrically for two weeks. The antidepressant effect of the two drugs was evaluated in terms of body weight, syrup partiality and open field test. The changes of glutamic acid (GLU), gama-aminobutyric acid (GABA) serum hypothalamic-pituitary-adrenal (HPA) axis transmitters, IL-1 and other cytokines in the hippocampus and cortex of rats in each group were determined. The difference in chemical composition between Dingzhixiaowan and Kaixinwan pills was analyzed. Results Dingzhixiaowan significantly increased the body weight, glycemic preference and open field scores of CUMS rats, reduced GLU content in the hippocampus and cortex of rats, increased GABA content, reduced HPA axis transmitters, and regulated serum cytokine levels. Kaixinwan increased GABA content in the hippocampus and cortex of model rats, but reduced serum cytokine levels.Conclusion Dingzhixiaowan pills have obvious antidepressant effect, but Kaixinwan pills do not in behavioral experiments. The antidepressant effect of Dingzhixiaowan may be related to the regulation of central neuron amino acid secretion, reversal of the hyperactivity of HPA axis, and reduction of the immune regulation of IL-1 and other cytokines. The antidepressant effect of the prescription may be closely related to the content of main chemical components such as ginsenosides.

Key words: depression, Dingzhixiaowan, Kaixinwan, chronic unpredictable mild stress

CLC Number:

R971R961

YANG Li, LIU Wanwan, ZHOU Xiaojiang, ZHANG Lan, DONG Xianzhe, LIU Ping. Antidepressant Effects and Mechanism of Dingzhixiaowan and Kaixinwan on CUMS Model Rats[J]. Chinese Journal of Pharmacovigilance, 2021, 18(12): 1138-1143.

References

[1] Li MH, Zhang J, Zhao RQ, et al.Effect of six class of Kaixin San formulas on pharmacological and preliminary mechanism of Alzheimer’s disease mice[J]. China Journal of Chinese Materia Medica(中国中药杂志),2016,7(41): 1269-1274.
[2] Malhi GS, Mann JJ.Depression[J]. Lancet, 2018, 392: 2299-2312.
[3] WHO. The global burden of disease: 2004 update[M]. Geneva: World Health Organization, 2008.
[4] Rahman AS, Aziz A, Jamal Q, et al.Prevalence of recognised and unrecognised depression among medical and surgical patients in a tertiary care hospital[J]. J Pak Med Assoc, 2015, 65(12): 1320-1324.
[5] Ignácio ZM, da Silva RS, Plissari ME, et al. Physical exercise and neuroinflammation in major depressive disorder[J]. Mol Neurobiol, 2019, 56(12): 8323-8335.
[6] Duman RS, Sanacora G, Krystal JH.Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments[J]. Neuron, 2019, 102(1): 75-90.
[7] Abdallah CG, Sanacora G, Duman RS, et al.The neurobiology of depression, ketamine and rapid-acting antidepressants: is it glutamate inhibition or activation?[J]. Pharmacol Ther, 2018, 190: 148-158.
[8] Wierońska JM, Pilc A.Depression and schizophrenia viewed from the perspective of amino acidergic neurotransmission: antipodes of psychiatric disorders[J]. Pharmacol Ther, 2019, 193: 75-82.
[9] Keller J, Gomez R, Williams G, et al.HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition[J]. Mol Psychiatry, 2017, 22(4): 527-536.
[10] Bollen J, Trick L, Llewellyn D, et al.The effects of acute inflamm-ation on cognitive functioning and emotional processing in humans: A systematic review of experimental studies[J]. J Psychosom Res, 2017, 94(3): 47-55.
[11] Jia Y, Liu L, Sheng C, et al.Increased serum levels of cortisol and inflammatory cytokines in people with depression[J]. J Nerv Ment Dis, 2019, 207(4): 271-276.
[12] Dong XZ, Wang DX, Yu BY, et al.Kai-xin-san, a traditional Chinese medicine formulation, exerts antidepressive and neuroprotective effects by promoting pCREB upstream pathways[J]. Exp Ther Med, 2016, 12(5): 3308-3314.
[13] Cao C, Xiao J, Liu M, et al.Active components, derived from Kai-xin-san, a herbal formula, increase the expressions of neurotrophic factor NGF and BDNF on mouse astrocyte primary cultures via cAMP-dependent signaling pathway[J]. J Ethnopharmacol, 2018, 224: 554-562.
[14] Zhu Y, Chao C, Duan X, et al.Kai-Xin-San series formulae alleviate depressive-like behaviors on chronic mild stressed mice via regulating neurotrophic factor system on hippocampus[J]. Sci Rep, 2017, 7(1): 1467.
[15] Yan JJ, Liu M, Hu Y, et al.The effect and mechanism of Dingzhi Xiaowan on scopolamine-induced learning and memory impairment in mice[J]. China Journal of Chinese Materia Medica(中国中药杂志), 2012, 21(37): 3293-3296.
[16] Dong XZ, Li ZL, Zheng XL, et al.A representative prescription for emotional disease, Ding-zhi-xiao-wan restores 5-HT system deficit through interfering the synthesis and transshipment in chronic mild stress-induced depressive rats[J]. J Ethnopharmacol, 2013, 150(3): 1053-1061.
[17] Xu L, Mu LH, Peng J, et al.UPLC-Q-TOF-MS(E) analysis of the constituents of Ding-zhi-xiao-wan, a traditional Chinese antidepressant, in normal and depressive rats[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2016,1026: 36-42.