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Original Article | Open Access

Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway

Shuling Liua,1, Fafeng Chenga,1, Beida Renb,c, Wenxiu Xua, Congai Chena, Chongyang Mad, Xiaole Zhanga, Feifei Tanga, Qingguo Wanga, Xueqian Wanga( )
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, China
Dongzhizmen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China
Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, China
School of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, China

Peer review under responsibility of Beijing University of Chinese Medicine.

1 These authors have contributed equally to this work.

Show Author Information

Abstract

Objective

The Qinzhi Zhudan formula (QZZD) exhibits a prominent therapeutic effect in the treatment of vascular dementia (VaD). This study combined a network pharmacology approach and experimental validation to identify the underlying biological mechanism of QZZD against VaD.

Methods

Male Wistar rats received bilateral common carotid artery occlusion (BCCAO) surgery, and after 4 weeks of intragastric administration of QZZD, the therapeutic effect was assessed using the Morris water maze test and cerebral blood flow (CBF) assessment. Hematoxylin and eosin staining, Nissl staining, and electron microscopy were used to measure the histopathological changes in the neurons of rats. The effect of QZZD treatment on hippocampal neurotransmitters was assessed by high-performance liquid chromatography with electrochemical detection and liquid chromatography mass spectrometry. Immunofluorescence was used to observe VaD-induced microglia activation. The inflammatory cytokine levels were assessed by enzyme linked immunosorbent assay. Western blot was used to examine the TNFR1-mediated TNF pathway, which was screened out by network pharmacology analysis.

Results

QZZD treatment alleviated pathological changes and neuronal damage in VaD rats and attenuated their cognitive impairment. In addition, QZZD increased CBF and the expression of acetylcholine and 5-hydroxytryptamine in the hippocampal region. Notably, QZZD inhibited microglial activation and the expression of IL-6 and TNF-α. Network pharmacology and western blot indicated that QZZD inhibited the levels of TNFR1, NF-κBp65, p-ERK, TNF-α, and IL-6, which are related to the TNFR1-mediated TNF signaling pathway.

Conclusion

QZZD clearly improved learning and memory function, reduced brain pathological damage, elevated CBF and hippocampal neurotransmitter levels, and alleviated neuroinflammation of VaD rats partly by inhibiting the TNFR1-mediated TNF pathway, indicating its potential value in the clinical therapy of VaD.

Keywords

MicrogliaCerebral blood flowVascular dementiaNeuroinflammationNetwork pharmacologyInflammatory cytokinesTNF signaling PathwayChronic cerebral ischemia

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Journal of Traditional Chinese Medical Sciences
Volume 9 Issue 3,
July 2022
Pages 298-310
DOI: 10.1016/j.jtcms.2022.06.011
Cite this article:
Liu S, Cheng F, Ren B, et al. Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway. Journal of Traditional Chinese Medical Sciences, 2022, 9(3): 298-310. https://doi.org/10.1016/j.jtcms.2022.06.011

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Received: 23 March 2022
Revised: 13 June 2022
Accepted: 14 June 2022
Published: 17 June 2022
© 2022 Beijing University of Chinese Medicine.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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