Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway
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 r...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-07-01
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| Series: | Journal of Traditional Chinese Medical Sciences |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S209575482200059X |
| _version_ | 1797758577223401472 |
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| author | Shuling Liu Fafeng Cheng Beida Ren Wenxiu Xu Congai Chen Chongyang Ma Xiaole Zhang Feifei Tang Qingguo Wang Xueqian Wang |
| author_facet | Shuling Liu Fafeng Cheng Beida Ren Wenxiu Xu Congai Chen Chongyang Ma Xiaole Zhang Feifei Tang Qingguo Wang Xueqian Wang |
| author_sort | Shuling Liu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-12T18:32:00Z |
| format | Article |
| id | doaj.art-7882254a73844f28a2c6b342806c0c9f |
| institution | Directory Open Access Journal |
| issn | 2095-7548 |
| language | English |
| last_indexed | 2024-03-12T18:32:00Z |
| publishDate | 2022-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Traditional Chinese Medical Sciences |
| spelling | doaj.art-7882254a73844f28a2c6b342806c0c9f2023-08-02T08:17:01ZengElsevierJournal of Traditional Chinese Medical Sciences2095-75482022-07-0193298310Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathwayShuling Liu0Fafeng Cheng1Beida Ren2Wenxiu Xu3Congai Chen4Chongyang Ma5Xiaole Zhang6Feifei Tang7Qingguo Wang8Xueqian Wang9School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaDongzhizmen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China; Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Capital Medical University, Beijing, 100069, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, ChinaSchool of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S209575482200059XVascular dementiaNeuroinflammationInflammatory cytokinesMicrogliaTNF signaling PathwayNetwork pharmacology |
| spellingShingle | Shuling Liu Fafeng Cheng Beida Ren Wenxiu Xu Congai Chen Chongyang Ma Xiaole Zhang Feifei Tang Qingguo Wang Xueqian Wang 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 Vascular dementia Neuroinflammation Inflammatory cytokines Microglia TNF signaling Pathway Network pharmacology |
| title | Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway |
| title_full | Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway |
| title_fullStr | Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway |
| title_full_unstemmed | Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway |
| title_short | Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway |
| title_sort | qinzhi zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the tnfr1 mediated tnf pathway |
| topic | Vascular dementia Neuroinflammation Inflammatory cytokines Microglia TNF signaling Pathway Network pharmacology |
| url | http://www.sciencedirect.com/science/article/pii/S209575482200059X |
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