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T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

Neural Regeneration Research 2025年第5期20卷 1277-1292页

作者： Yuxiao Zheng Zilin Ren Ying Liu Juntang Yan Congai Chen Yanhui He Yuyu Shi fafeng cheng Qingguo Wang Changxiang Li Xueqian Wang School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijingChina Library Beijing University of Chinese MedicineBeijingChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue *** the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the *** an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune *** review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic *** found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic ***1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain ***2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain *** interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke *** trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic ***,such studies have been relatively infrequent,and clinical experience is still *** summary,in ischemic stroke,T cell subsets and activated micro

关键词： brain immune inflammation interaction ischemic stroke mechanism microglia neuron secondary injury T cells

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Therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion injury

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Neural Regeneration Research 2011年第21期6卷 1605-1611页

作者： fafeng cheng Wenting Song Xianggen Zhong Yi Lu Shaoying Guo Dong Wang Weipeng Zhao Qingguo Wang College of Basic Medicine Beijing University of Chinese Medicine Beijing 100029 China Xiyuan Hospital of China Academy of Chinese Medical Sciences Beijing 100091 China

The time window in which a drug is effective varies between drugs. The present study investigated the therapeutic window of Qingkailing injection for focal cerebral ischemia/reperfusion in mice. Animals underwent middle cerebral artery occlusion and were injected with Qingkailing （1.5, 3, 6 mL/kg）. Infarct volume and neurological function were assessed after 24 hours of ischemia. In addition, to establish the therapeutic time window, mice were injected with 3 mL/kg Qingkailing at 0, 1, 3, 4, 6, 9 and 12 hours after occlusion. Results revealed that Qingkailing injection significantly reduced infarct volume and improved neurological function in model mice after cerebral infarction for up to 9 hours, demonstrating that the therapeutic window of Qingkailing injection can extend to 9 hours for cerebral ischemia/reperfusion in mice.

关键词： focal cerebral ischemia Qingkailing injection time window infarct volume

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Liangxue Xiaoban decoction and its disassembled prescriptions ameliorate psoriasis-like skin lesions induced by imiquimod in mice via T cell regulation

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Journal of Traditional Chinese Medical Sciences 2022年第4期9卷 409-419页

作者： Feifei Tang Shuling Liu fafeng cheng Qingguo Wang Xueqian Wang School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing102488China

Objective:To explore the therapeutic capacity of the Liangxue Xiaoban(LXXB)decoction and its disassembled prescriptions in the modulation of T cell subsets and recurrence-related indexes of psoriasis using a psoriasis-like mouse ***:The psoriasis model was generated by the treatment of BALB/c mice(n=48)with *** were divided into six groups:control,psoriasis model,tripterygium glycosides,LXXB decoction,Liangxue decoction,and Qingqi *** the intervention period,the interleukin(IL)-17A,IL-22,and interferon-γ levels in mice were examined and hematoxylin and eosin staining was conducted to determine pathological changes in the skin tissues.T cell subset changes in the skin-draining lymph nodes were analyzed using flow cytometry,and the expression levels of the associated transcription factors and recurrence-related indexes in the skin tissues were determined using a polymerase chain ***:LXXB decoction attenuated the levels of CD8^(+)T,Th17,and Th1 cells and induced an increase in the Th2 and Treg cell *** disassembled prescriptions promoted or inhibited specific subsets of T cells to improve the symptoms of ***,the LXXB and Liangxue decoctions suppressed the expression of IL-22 at both the gene and protein levels and restored the CD103 and IL-15 expressions in the skin tissue to the normal ***:LXXB decoction exerted significant immunoregulatory effects on T cell subsets and improved the recurrence-related ***,the Liangxue prescription appeared to have a therapeutic advantage in terms of Th17 modulation and psoriasis recurrence,while the Qingqi prescription performed better in Treg immunoregulation.

关键词： Psoriasis T cells Recurrence Liangxue Xiaoban decoction Disassembled prescription Tripterygium glycoside

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Paeoniflorin inhibits lipopolysaccharide-induced inflammation in LO2 cells by regulating RhoA/NLRP3 pathway

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Journal of Traditional Chinese Medical Sciences 2021年第2期8卷 161-165页

作者： Haixia Liu fafeng cheng Feifei Tang Yifang Wang Shuling Liu Xueqian Wang School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing102488China

Background:Inflammation is an essential component of liver ***(PF),a monoterpenoid component derived from peony root(Paeonia lactiflora Pall.),has anti-inflammatory,immunoregulatory,and hepatoprotective ***,whether PF affects liver inflammation and its underlying mechanisms is *** this study,we investigated the effects of PF on lipopolysaccharide(LPS)-induced inflammation in LO2 cells and the underlying molecular ***:LPS was used to induce *** PF pretreatment for 2 h,the cells were treated with PF and *** counting kit-8 was used to measure cell *** necrosis factor-a(TNF-a)and interleukin(IL)-6 were tested by Enzyme-linked immunosorbent *** blot was used to evaluate TNF-a,Ras homolog family member A(RhoA),NOD-,LRR-and pyrin domain-containing protein 3(NLRP3),apoptosis-associated speck-like protein containing a CARD(ASC),caspase-1,and IL-1b proteins ***:In LPS-induced LO2 cells,PF reduced TNF-a and IL-6 inflammatory cytokine production in a dose-dependent ***-induced TNF-a expression was also suppressed by *** addition,PF significantly inhibited LPS-induced RhoA activation(P=.0014).Finally,PF suppressed LPS-induced NLRP3 inflammasome activation by downregulating NLRP3,ASC,caspase-1,and IL-1b ***:These findings suggest that PF alleviates inflammation induced by LPS and further suggest the anti-inflammatory effect of PF may follow via reduced RhoA and NLRP3 inflammasome activity.

关键词： Paeoniflorin Lipopolysaccharide Inflammation RhoA NLRP3 inflammasome

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Possible mechanisms underlying treatment of Alzheimer’s disease with Traditional Chinese Medicine: active components, potential targets and synthetic pathways of Bulao Elixir

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Journal of Traditional Chinese Medicine 2020年第3期40卷 484-496页

作者： Ren Beida cheng fafeng Wang Xueqian Wan Yuxiang Ji Wenting Du Xin Zhang Shuang Liu Shilling Ma Chongyang Xiong Yiliang Hao Gaoting Wang Qingguo School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 100029China The Third Affiliated Hospital Beijing University of Chinese MedicineBeijing 100029China School of Chinese Classics Beijing University of Chinese MedicineBeijing 100029China Affiliated Hospital of Shanxi University of Traditional Chinese Medicine Taiyuan 030000China

OBJECTIVE: To elucidate the mechanisms underlying the treatment of Alzheimer’s disease(AD) with Traditional Chinese Medicine(TCM), by examining the active components, potential targets and synthetic pathways of Bulao Elixir(BLE).METHODS: The Absorption, Distribution, Metabolism, Excretion(ADME)/Toxicology(T) calculation was used to screen the active components of Bulao Elixir. Based on the TCM Systems Pharmacology Analysis Platform(TCMSP database) and a text mining tool(GoPubMed database), we predicted and screened the active components of Bulao Elixir and its therapeutic targets for AD. Using the Database for Annotation, Visualization and Integrated Discovery(DAVID), we obtained the targets for AD. Cytoscape software was used to establish a network map of the active component-target and target-pathway of Bulao Elixir. Gene function, related biological processes and signaling pathways were analyzed using the DAVID ***: Twelve active components were selected from 196 components of Bulao Elixir. Among 2209 targets, 102 effective targets were selected, and 30 important targets were identified via matching with the disease targets. After further analysis, 14 core targets were identified. Enrichment analysis revealed that most of these important targets were involved in multiple biological processes, including apoptosis, inflammatory reactions, and cell regulation cycles. The synthetic pathways for AD treatment were identified after analyzing and confirming the relevant pathways, providing potentially useful information for diagnosis and treatment methods for ***: The current study elucidated the potential treatment mechanisms of Bulao Elixir in AD using network pharmacology, providing a foundation for further clarification of its treatment targets.

关键词： Alzheimer disease Pharmacology Components Targets Pathway Bulao Elixir

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Sini powder ameliorates the inflammatory response in rats with stress-induced non-alcoholic fatty liver disease by inhibiting the nuclear factor kappa-B/pyrin domain-containing protein 3 pathway

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Journal of Traditional Chinese Medicine 2020年第2期40卷 253-266页

作者： Mu Jie cheng fafeng Wang Qingguo Wang Xueqian Zhu Wenxiang Ma Chongyang Yin Xiangjun Ren Beida Lian Yajun Du Xin Zhang Haixia Liu Shuling Zhang Shuang Teaching and Research Office of Clinical Foundation of Chinese Medicine School of Basic MedicineInnovation Team of"Basic Research on the Application of Classical Formulas"Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE: To evaluate the effectiveness of Sini powder for the treatment of non-alcoholic fatty liver disease(NAFLD) in rats and the molecular mechanisms ***: A rat model of stress-induced NAFLD was established by a combination of long-term tethering and feeding of a high-fat, high-calorie diet. These rats were then intragastrically administered with either simvastatin, Sini powder, or vehicle for 1 week. The body mass and field test scores for each group were recorded weekly. Serum aspartate aminotransferase and alanine aminotransferase activities, and triglyceride, total cholesterol,and free fatty acid concentrations were *** tissue histopathology was examined on hematoxylin and eosin-stained paraffin sections and oil red O-stained frozen sections. The hepatic m RNA expression of nuclear factor kappa-B(NF-κB),NOD-, LRR-, and pyrin domain-containing protein 3(NLRP3), apoptosis-associated speck-like protein containing CARD(ASC), and caspase-1 were measured by reverse transcription-polymerase chain reaction(RT-PCR). The hepatic protein concentrations of NF-κB and NLRP3, ASC, caspase-1, interleukin-1β(IL-1β), interleukin-6(IL-6), and the serum concentrations of IL-1β and IL-6 were measured by enzyme-linked immunosorbent ***: Compared with the Blank group, rats in the Compound model group showed significant pathologic manifestations of NAFLD, and the expression of NF-κB, NLRP3, ASC, caspase-1, IL-1βand IL-6 were significantly higher(all P < 0.01). Both simvastatin and Sini powder significantly ameliorated the NAFLD pathology and the abnormal expression of NF-κB, NLRP3, ASC, caspase-1, IL-1β, and IL-6(all P < 0.01).CONCLUSION: Sini powder inhibits the inflamma-tory response in rats with NAFLD, which is mediated by NF-κB/NLRP3, IL-1β, and IL-6, reduces the effects of psychological stress, and improves lipid metabolism. Therefore, Sini powder may be effective for the treatment of stress-related NAFLD through multiple mechanisms.

关键词： Non-alcoholic fatty liver Stress,psychological NLR family,pyrin domain-containing 3 protein NF-kappa B Interleukins Sini powder

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Molecular mechanism of non-alcoholic fatty liver disease induced and aggravated by chronic stress through HSL/ATGL-FFA which promotes fat mobilization

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Journal of Traditional Chinese Medical Sciences 2019年第4期6卷 315-324页

作者： Jie Mu Xueqian Wang Qingguo Wang fafeng cheng Wenxiang Zhu Changxiang Li Chongyang Ma Changming Zhai Yajun Lian Xin Du School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 102488China

Objective:To study the effects of social stress(CS)and social stress combined with high-fat diet on fat mobilization as a candidate mechanism for the induction or aggravation of non-alcoholic fatty liver disease(NAFLD).Methods:Thirty-two male Wistar rats(250±10 g)were randomly allocated to a blank control group(BC),a high-fat diet group(HFD),a CS group,and a combined CS and high-fat diet group(CS t HFD).Rats were sacrificed and tissues were collected after 8 *** and body mass were measured and used to calculate the liver *** aspartate aminotransferase(AST),alanine aminotransferase(ALT),and free fatty acids(FFAs)were *** sections were examined microscopically after oil red O and hematoxylin and eosin *** relative mRNA expression of acetyl-CoA carboxylase(ACCase),hydroxymethylglutaryl coenzyme A(HMG-CoA)reductase in liver,and hormone-sensitive lipase(HSL),and adipose triglyceride lipase(ATGL)in subcutaneous adipose tissue,were measured by real-time *** liver concentrations of triglyceride,reactive oxygen species,and ACCase were measured by ELISA and HSL activity was determined using ***:NAFLD developed in the CS,HFD,and CS t HFD groups,with the most severe NAFLD being in the CS t HFD *** AST,ALT,and FFA,liver index,and hepatic triglyceride,FFA,and tumor necrosis factor-a were significantly higher in both the CS and CS t HFD ***,food intake and ACCase mRNA expression were *** mRNA expression of HSL and ATGL in adipose tissue was much higher,and HSL activity was higher in the CS group than in the BC group,and in the CS t HFD group than in the HFD ***:We have successfully established two models of stress-induced NAFLD,suggesting stress can induce and aggravate NAFLD by promoting fat mobilization through upregulation of HSL and ATGL.

关键词： Non-alcoholic fatty liver disease Chronic stress Fat mobilization Free fatty acid

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

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Journal of Traditional Chinese Medical Sciences 2022年第3期9卷 298-310页

作者： Shuling Liu fafeng cheng Beida Ren Wenxiu Xu Congai Chen Chongyang Ma Xiaole Zhang Feifei Tang Qingguo Wang Xueqian Wang School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing102488China Dongzhizmen Hospital Beijing University of Chinese MedicineBeijing100700China Institute for Brain Disorders Beijing University of Chinese MedicineBeijing100700China School of Traditional Chinese Medicine Capital Medical UniversityBeijing100069China

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 ***: Male Wistar rats received bilateral common carotid artery occlusion(BCCAO) surgery, and after4 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 *** 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 ***: 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-a. Network pharmacology and western blot indicated that QZZD inhibited the levels of TNFR1, NF-κBp65, p-ERK, TNF-a, and IL-6, which are related to the TNFR1-mediated TNF signaling ***: 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.

关键词： Vascular dementia Neuroinflammation Inflammatory cytokines Microglia TNF signaling Pathway Network pharmacology Cerebral blood flow Chronic cerebral ischemia

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Mechanism underlying effect of Chaihu Shugan San(柴胡疏肝散)on major depressive disorder:a network pharmacology-based study

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Journal of Traditional Chinese Medicine 2021年第2期41卷 338-348页

作者： MU Jie ZHANG Shuang TANG Feifei LIU Shuling ZHANG Qianyi DU Qianlei WANG Xueqian WANG Qingguo cheng fafeng Clinical basic teaching and Research Office of Traditional Chinese Medicine Chengdu University of Traditional Chinese MedicineWenjiang DistrictChengdu 611137China Innovation Team of"Basic Research on Application of Classical Prescription" Teaching and Research Department of Clinical Foundation of Chinese MedicineSchool of Basic Medical SciencesBeijing University of Chinese MedicineBeijing 100029China

OBJECTIVE:To investigate the mechanism underpinning the effect of Chaihu Shugan San(柴胡疏肝散,CHSGS)on major depressive disorder(MDD).METHODS:We searched the compound components of from seven herbal ingredients of CHSGS from TCMSP,SymMap,ETCM,NPASS databases,and the chemical structure of the compound from PubChem,and collected the compound targets from TCMSP and TargetNet databases,and MDD-related targets from DiseaseGene *** established protein-protein interaction in the STRING *** gene mapping,topology analysis and enrichment analysis,the core targets and pathways of CHSGS for MDD,and the involved biological processes(BP),cell components(CC),and molecular functions(MF)were ***:We collected a total of 1135 CHSGS *** screening by ADME standards and the five rules of Ribinski,we obtained 99 different chemical components with different chemical structures,and related targets of 183 different CHSGS *** the DiseaseGene Network,a total of 740 relevant targets for MDD were *** gene mapping and topological analysis,62 related targets of CHSGS for MDD,24 targets with topological Chinese herbal medicine were *** enrichment analysis,10 relevant pathways and 3 core pathways were obtained with the involvement of 127 BP,27 CC,and 43 ***:There are multiple targets and signaling pathways are involved in the action of CHSGS in the treatment of MDD.

关键词： Depressive disorder,major Pharmacology Chaihu Shugan San

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Biologic basis of TCM syndromes and the standardization of syndrome classification

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Journal of Traditional Chinese Medical Sciences 2014年第2期1卷 92-97页

作者： fafeng cheng Xueqian Wang Wenting Song Yi Lu Xiaoli Li Hanrui Zhang Qingguo Wang College of Basic Medicine Beijing University of Chinese MedicineBeijing 100029China Xiyuan Hospital of China Academy of Chinese Medical Sciences Beijing 100091China School of Humanities Beijing University of Chinese MedicineBeijing 100029China Perelman School of Medicine University of PennsylvaniaPhiladelphiaPA 19104USA

Traditional Chinese medicine(TCM)syndrome is an integral and essential component of TCM theory,and goes beyond philosophic *** article reviews the concept of TCM syndromes and summarizes research findings on the biologic foundation of *** addition,insight is provided into the promotion of standardization of syndrome classification by enforcing uniformity of TCM terminology,applying standardized diagnostic criteria and operating procedures to minimize subjective *** incorporating interdisciplinary approaches such as data mining and structure modeling,as well as integrating findings on biomarker research are *** is made of the fundamental TCM aspects of syndrome elements,symptoms,phenotypic features,as well as diseases,to form an integral process in the diagnostic *** believe that better understanding of the biologic basis of the TCM syndrome and standardization of syndrome classification will improve diagnosis,which in turn will enhance therapeutic efficacy and disease prognosis.

关键词： Traditional Chinese medicine Syndrome Syndrome elements Syndrome differentiation

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