Shuling Liu , Fafeng Cheng , Beida Ren , Wenxiu Xu , Congai Chen , Chongyang Ma , Xiaole Zhang , Feifei Tang , Qingguo Wang , Xueqian Wang
{"title":"芩栀助丹方改善血管性痴呆大鼠记忆，部分通过抑制tnfr1介导的TNF通路缓解神经炎症","authors":"Shuling Liu , Fafeng Cheng , Beida Ren , Wenxiu Xu , Congai Chen , Chongyang Ma , Xiaole Zhang , Feifei Tang , Qingguo Wang , Xueqian Wang","doi":"10.1016/j.jtcms.2022.06.011","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>","PeriodicalId":36624,"journal":{"name":"Journal of Traditional Chinese Medical Sciences","volume":"9 3","pages":"Pages 298-310"},"PeriodicalIF":0.0000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S209575482200059X/pdfft?md5=f1346d900933d790d7dc1685aea63410&pid=1-s2.0-S209575482200059X-main.pdf","citationCount":"3","resultStr":"{\"title\":\"Qinzhi Zhudan formula improves memory and alleviates neuroinflammation in vascular dementia rats partly by inhibiting the TNFR1-mediated TNF pathway\",\"authors\":\"Shuling Liu , Fafeng Cheng , Beida Ren , Wenxiu Xu , Congai Chen , Chongyang Ma , Xiaole Zhang , Feifei Tang , Qingguo Wang , Xueqian Wang\",\"doi\":\"10.1016/j.jtcms.2022.06.011\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>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.</p></div><div><h3>Methods</h3><p>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.</p></div><div><h3>Results</h3><p>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.</p></div><div><h3>Conclusion</h3><p>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.</p></div>\",\"PeriodicalId\":36624,\"journal\":{\"name\":\"Journal of Traditional Chinese Medical Sciences\",\"volume\":\"9 3\",\"pages\":\"Pages 298-310\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-07-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S209575482200059X/pdfft?md5=f1346d900933d790d7dc1685aea63410&pid=1-s2.0-S209575482200059X-main.pdf\",\"citationCount\":\"3\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Traditional Chinese Medical Sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S209575482200059X\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Traditional Chinese Medical Sciences","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S209575482200059X","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
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 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.
期刊介绍：
Production and Hosting by Elsevier B.V. on behalf of Beijing University of Chinese Medicine Peer review under the responsibility of Beijing University of Chinese Medicine. Journal of Traditional Chinese Medical Sciences is an international, peer-reviewed publication featuring advanced scientific research in Traditional Chinese medicine (TCM). The journal is sponsored by Beijing University of Chinese Medicine and Tsinghua University Press, and supervised by the Ministry of Education of China. The goal of the journal is to serve as an authoritative platform to present state-of-the-art research results. The journal is published quarterly. We welcome submissions of original papers on experimental and clinical studies on TCM, herbs and acupuncture that apply modern scientific research methods. The journal also publishes case reports, reviews, and articles on TCM theory and policy.
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