1.Ligustilide improves demyelination of dMCAO mouse model by inhibiting inflammation through AIM2/caspase-1 signaling pathway
Ya-jie LIANG ; Jian LIU ; Ying CHEN ; Zi-wei ZHANG ; Meng PU ; Yi-bin TANG ; Hai-fei ZHANG ; Guo-bin SONG ; Cun-gen MA ; Qing WANG
Chinese Pharmacological Bulletin 2025;41(5):851-860
Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P<0.05),the expression of IBA1 in CX decreased(P<0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P<0.01).The results of ELISA showed that the levels ofTNF-α(P<0.01),IL-6(P<0.01),IL-1β(P<0.05)and IL-17A(P<0.01)significantly decreased,while the ex-pression of BDNF increased(P<0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P<0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.
2.Ligustilide improves demyelination of dMCAO mouse model by inhibiting inflammation through AIM2/caspase-1 signaling pathway
Ya-jie LIANG ; Jian LIU ; Ying CHEN ; Zi-wei ZHANG ; Meng PU ; Yi-bin TANG ; Hai-fei ZHANG ; Guo-bin SONG ; Cun-gen MA ; Qing WANG
Chinese Pharmacological Bulletin 2025;41(5):851-860
Aim To explore the mechanism of ligustil-ide(LIG)improving demyelination by inhibiting in-flammatory response in mice with distal middle cerebral artery occlusion(dMCAO)through AIM2/caspase-1 signal pathway.Methods Thirty C57BL/6N male mice were randomly divided into three groups:sham operation group(Sham group,n=10),model group(dMCAO group,n=10)and treatment group(LIG group,n=10).The dMCAO mouse model was estab-lished by electrocoagulation in dMCAO group and LIG group.The mice were scored by Longa after waking up,and the changes of cerebral blood flow were moni-tored by laser speckle blood flow imaging system after dMCAO.One hour after modeling,LIG(30 mg·kg-1·d-1)was injected intraperitoneally in LIG group,and the same amount of normal saline was injected in sham group and dMCAO group for one week until the end of the experiment.The mice in each group were stained with TTC,and the brain injury was observed pathologically.Fatigue turning bar test and open field test were used to evaluate the motor function and anxie-ty degree of mice,and then the brain tissues of mice were taken for black gold staining to compare the chan-ges of myelin sheath in each group.Immunofluores-cence staining was used to detect the average fluores-cence intensity of MBP,IBA1 and GFAP in CC,CPU and CX regions of mouse brains.ELISAwas used to de-tect the contents of TNF-α,IL-6,IL-1 β,IL-17A and BDNF in brain tissue proteins of mice.Western blot-ting was used to detect the protein expressions of AIM2,caspase-1 and ASC-in each group.Results Compared with the dMCAO group,the infarct area was reduced,the behavior was significantly improved and the demyelination was reduced in the LIG group.The expression of MBP protein in CC,CPU and CX regions increased(P<0.05),the expression of IBA1 in CX decreased(P<0.01),and the expression of GFAP in-creased in CC,CPU and CX regions(P<0.01).The results of ELISA showed that the levels ofTNF-α(P<0.01),IL-6(P<0.01),IL-1β(P<0.05)and IL-17A(P<0.01)significantly decreased,while the ex-pression of BDNF increased(P<0.05).The protein expression levels of AIM2,caspase-1 and ASC in mouse brain decreased after treatment(P<0.01).Conclusion LIG has a protective effect on demyelina-tion in dMCAO mice,which may be related to the inhi-bition of AIM2/caspase-1 signaling pathway and in-flammation and to the promotion of BDNF secretion.
3.Promotion mechanism of astragaloside on axon repair and regeneration in experimental autoimmune encephalomyelitis mice
Jian-Chun LIU ; Hong-Zhen ZHANG ; Qing WANG ; Hui-Jie FAN ; Li-Juan SONG ; Zhi CHAI ; Cun-Gen MA
Medical Journal of Chinese People's Liberation Army 2024;49(8):914-921
Objective To investigate the effects of astragaloside Ⅳ(AS-Ⅳ)on axon growth inhibitory factor A(Nogo-A)and its downstream pathway protein RHO-associated coiled spiral kinase 2(ROCK2)in experimental autoimmune encephalomyelitis(EAE)mice,and to explore the mechanism by which it promotes axon repair and regeneration.Methods EAE model was induced in C57BL/6 female mice by subcutaneous injection of myelin oligodendrocyte glycoprotein 35-55(MOG35-55).Mice were randomly divided into EAE group and AS-Ⅳ group(n=8 per group).EAE group received intraperitoneal injection of PBS on the 3rd day post-immunization,while AS-Ⅳ group was administered AS-Ⅳ at a dosage of 30mg/(kg.d)once daily,0.2 ml per injection,for 25 consecutive days.On the 28th day post-immunization,the expression levels of growth-associated protein 43(GAP-43),neuronal core antigen(NeuN),microtubule associated protein 2(MAP-2),glial fibroacidic protein(GFAP),and Iba1 in the spinal cord were detected using immunofluorescence assay.Real-time fluorescence quantitative PCR(qRT-PCR)was conducted to detect mRNA expression levels of GAP-43,Nogo-A,and Nogo receptor(NgR)genes.Western blotting was utilized to determine the expression levels of GAP-43,Nogo-A,ROCK2,phosphorylated myosin phosphatase(p-MYPT1),B-lymphoblastoma-2(Bcl-2),and Bcl-2 associated X protein(Bax).Results Compared with EAE group,AS-Ⅳ treatment significantly reduced the positive cell expression rates of Iba1 microglia and GFAP astrocyte in spinal cord(P<0.01 and P<0.001,respectively),while it also increased the positive expression rates of NeuN and MAP-2(P<0.001 and P<0.05,respectively).The treatment also upregulated the expression level of anti-apoptotic factor Bcl-2(P<0.001)and downregulated the expression level of pro-apoptotic factor Bax(P<0.05),leading to an increase in Bcl-2/Bax ratio(P<0.05).Furthermore,AS-Ⅳ enhanced the expression of GAP-43 protein(P<0.05)and decreased the mRNA expression levels of neuroregeneration inhibitor Nogo receptor(NgR)and ROCK2 gene(P<0.001,P<0.05,respectively);as well as decreased the expression levels of Nogo-A,ROCK2 and p-MYPT1 proteins(P<0.05,P<0.001).Conclusion AS-Ⅳ may inhibit the activation of microglia and astrocytes and neuronal apoptosis in EAE mice by inhibiting Nogo-A and downstream pathway ROCK 2,thereby promoting the expression of GAP-43,NeuN and MAP-2,alleviating neuronal damage,and facilitating axon repair and regeneration.
4.Proanthocyanin B2 inhibits oxidative stress and alleviates H2O2 induced damage to human oligodendrocytes through NRF2/HO-1/xCT/GPX4 axis
Jian LIU ; Ying CHEN ; Ya-Jie LIANG ; Meng PU ; Zi-Wei ZHANG ; Lu-Lu ZHENG ; Zhi CHAI ; Ying XIAO ; Cun-Gen MA ; Qing WANG
Chinese Pharmacological Bulletin 2024;40(9):1735-1743
Aim To explore the protective effect of an-thocyanin B2(PCB2)on hydrogen peroxide(H2O2)induced oxidative damage and apoptosis in human oli-godendrocytes(MO3.13)and the underlying mecha-nism.Methods The optimal concentration of H2O2 and PCB2 for action was screened,and divided into normal group,PCB2 group(100 mg·L-1 PCB2 treat-ment for 24 hours),H2 O2 model group(500 μmol·L-1 H2O2 treatment for 24 hours),and H2O2+PCB2 group(500 μmol·L-1 H2O2 and 100 mg·L-1 PCB2 co-treated for 24 hours).FRAP method was used to detect the antioxidant capacity of PCB2;CCK-8 meth-od was used to detect the survival rate of cells in each group,while LDH method was used to assess cytotoxic-ity.Microenzyme-linked immunosorbent assay and ELISA were used to examine the levels of LDH,NO,H2O2,as well as the activities of CAT and SOD in each group of cells.Immunofluorescence and Western blot were used to detect the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4 in each group of cells.FerroOrange fluorescent probe was used to de-tect the intracellular content of ferrous ions(Fe2+).Results H2O2 could induce MO3.13 oxidative dam-age and lead to cell ferroptosis,while PCB2 could alle-viate MO3.13 oxidative damage and ferroptosis.Com-pared with the H2O2 model group,PCB2 intervention could significantly increase LDH content in MO3.13,reduce NO and H2O2 content,and improve SOD and CAT activity,and up-regulate the protein expression levels of NRF2,xCT,HO-1,ferritin,and GPX4.Conclusion PCB2 can enhance cellular antioxidant capacity and alleviate H2O2 induced MO3.13 oxidative damage through the NRF2/HO-1/xCT/GPX4 axis.
5. GLPS improves EAE demyelination through inhibition of TLR4/NF-KB pathway
Yan-Qing LI ; Qing WANG ; Zhi-Chao YANG ; Li-Juan SONG ; Jian-Chun LIU ; Cun-Gen MA ; Han-Bin WANG ; Li-Zhi YANG ; Bao-Guo XIAO
Chinese Pharmacological Bulletin 2023;39(10):1914-1920
Aim To explore the protective effects of ganoderma lucidum polysaccharides (GLPS) on experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS) and the underlying mechanism. Methods Thirty C57BL/6 mice were randomly divided into three groups: normal control group, EAE model group and GLPS group (5 mg • kg
6. Procyanidin B2 protects H
Yi-Wei DONG ; Zhi-Chao YANG ; Wei-Jia JIANG ; Jian-Chun LIU ; Wan-Fang YANG ; Shu-Wen YUAN ; Xiao-Hui LI ; Cun-Gen MA ; Qing WANG ; Bao-Guo XIAO
Chinese Pharmacological Bulletin 2023;39(9):1654-1661
Aim To explore the protective effect of proanthocyanidin B2 (PC-B2) on oxidative damage of PC 12 cells induced by hydrogen peroxide (H
7. Neuroprotective Mechanism of Buyang Huanwu Tang on Experimental Autoimmune Encephalomyelitis Mice
Jian-chun LIU ; Hong-zhen ZHANG ; Wen-juan GUO ; Zhi CHAI ; Jie-zhong YU ; Jing-wen YU ; Bao-guo XIAO ; Cun-gen MA
Chinese Journal of Experimental Traditional Medical Formulae 2019;25(14):55-61
Objective:To explore the neuroprotective effect and mechanism of Buyang Huanwu Tang (BYHWT) on experimental autoimmune encephalomyelitis (EAE) at different stages. Method:The 36 female C57BL/6 mice were immunized subcutaneously with myelin oligodendrocyte glycoprotein peptides (MOG35-55),then randomly divided into 9, 17, 28 d EAE control group. Each BYHWT group was orally given drugs on the 3rd day after immunization (50 g·kg-1·d-1), and EAE control group was given the same volume of normal saline in the same way once a day for 9, 17 and 28 d after immunization. The effect of BYHWT on EAE mice was observed with internationally accepted clinical score. Brain and spinal cord specimens were collected at 9, 17 and 28 d after immunization. The neuroprotective effect of BYHWT was observed by hematoxylin-eosin(HE)staining and solid blue staining (LFB). The expressions of BDNF and GAP-43 in spinal cord and brain were detected by Western blot. Result:After treatment, BYHWT can significantly inhibit myelitis cell infiltration and alleviate myelin loss. Compared with EAE group, the expression of Nogo-A in the spinal cord of each BYHWT group was significantly down-regulated (P<0.01), and the expression of BDNF in the spinal cord was significantly up-regulated (P<0.05, P<0.01) in the BYHWT group 17 and 28 d group compared with EAE group 17 and 28 d group. Compared with EAE 9, 17 d group, GAP-43 expression was significantly up-regulated in the spinal cord of BYHWT 9, 17 d group (P<0.01). Conclusion:BYHWT can improve the local nerve growth microenvironment and promote the expression of NTFs, reduce the expressions of neuroinhibitory factors, and play a role in neuroprotection.
8.Neuroprotective effect of fasudil combined with bone marrow-derived neural stem cells on mice with experimental autoimmune encephalomyelitis
bin Guo SONG ; ping Guo XI ; hua Yan LI ; shan Jia LI ; chun Jian LIU ; Zhi CHAI ; guo Bao XIAO ; xian Guang ZHANG ; gen Cun MA
Chinese Journal of Pathophysiology 2017;33(12):2113-2120
AIM: To explore the neuroprotective effect of fasudil combined with bone marrow -derived neural stem cells ( BM-NSCs) on the mice with experimental autoimmune encephalomyelitis ( EAE).METHODS: Female C57BL/6 mice (8~10 weeks old, n=32) were immunized with myelin oligodendrocyte glycoprotein 35-55 (MOG35-55) to establish chronic EAE model .The mice were randomly divided into control ( ddH2 O ) group, fasudil group , BM-NSCs group , and fasudil+BM-NSCs group .The clinical score and body weight were recorded every other day .The expression of neurotrophic factors was determined by immunofluorescence staining .RESULTS:In comparison with ddH2O group, fasud-il combined with BM-NSCs delayed onset and ameliorated severity of EAE .The numbers of brain-derived neurotrophic fac-tor, glial cell-derived neurotrophic factor , nerve growth factor , neurotrophin-3 and ciliary neurotrophic factor positive cells in fasudil group, BM-NSCs group and fasudil +BM-NSCs group were all increased in various extents .In particularly, the expression of these neurotrophic factors in fasudil +BM-NSCs group was significantly higher than that in the mice treated with fasudil or BM-NSCs alone (P<0.01).CONCLUSION:Fasudil combined with BM-NSCs promotes the expression of neurotrophic factors and improves microenvironment of central nervous system , thus playing a positive role in neural restora-tion and regeneration through a synergistic and superimposed effect .
9.Antimicrobial susceptibility pattern and epidemiology of male urinary tract infections in China, 2012
Gen-Jie RUAN ; Bo ZHENG ; Yu-Cun LIU
The Chinese Journal of Clinical Pharmacology 2015;(11):1007-1013,1021
Objective To investigate the bacterial distribution and resistance to antibiotic of male urinary tract infections in China,2012.Methods The urine specimens from the tertiary hospitals and the second class hospitals were routinely isolated and identified.Disc diffusion test, MIC test and E -test were used to detect the antimicrobial sensitivity.Results All the clinical stains isolated from 557 tertiary hospitals and 232 second class hospitals.A total of 61293 pathogenic strains were co-llected from male urine specimen, which included E.coli 20357strains ( 33.2%) , E.faecalis 5280 strains ( 8.6%) , K.pneumonia 5249 strains (8.6%) and E.faecium 4516 strains (7.4%).In tertiary hos-pital, The top four bacteria were E.coli, E.faecalis.K.pneumonia and E.faecium, and in second class hospitals were E.coli, P.aeruginosa, K.pneumonia and E.faecalis.The resistant rate of E.coli, K.pneumo-nia and E.cloaecae strains to cefotaxime were above 70%.The resistant rate to levofloxacin were 63.8%, 40.9%and 35.7%, respectively.The 4.2%and 4.0%of E.faecium isolates were resistant to vancomycin and teicoplanin, respectively.The 1.1% and 2.8% of E.faecalis isolates were resistant to vancomyicin and teicoplanin, respectively.Conclusion E.coli were predominant organism in male urinary tract infections in China.There were some difference in bacterial distribution and resistance between the tertiary hospitals and second class hospitals.
10.Effect of qingyi decoction in preventing post-endoscopic retrograde cholangiopancreatography pancreatitis and hyperamylasemia.
Cun-Gen LIU ; Da-Yue LENG ; Huan LIU
Chinese Journal of Integrated Traditional and Western Medicine 2009;29(7):607-610
OBJECTIVETo explore the preventive effect of Qingyi Decoction (QYD) on post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and hyperamylasemia.
METHODSOne hundred and twenty-five patients scheduled to receive ERCP were randomized by the digital table into three groups, two were medicated respectively with QYD (39 cases) and octreotide (42 cases), the other one was untreated for control (44 cases). Changes of blood levels of amylase, C-reactive protein (CRP), and interleukin-10 (IL-10), as well as the incidence of pancreatitis and hyperamylasemia was observed and compared.
RESULTSThe 4 h and 24 h post-operational blood amylase (U/L) was 132.03 +/- 75.29 and 153.15 +/- 78.69 in the QYD group, and 134.74 +/- 22.24 and 148.50 +/- 79.37 in the octreotide group, all were significantly lower than those in the control group (241.27 +/- 137.04 and 286.89 +/- 133.77), respectively. The 24 h CRP (mg/L) in both QYD and octreotide group (11.05 +/- 3.57 and 12.48 +/- 3.80) was also lower than that in the control group (17.70 +/- 4.93, P < 0.05), while the 24 h IL-10 (ng/L) in the QYD group (105.00 +/- 31.85) was higher than that in the octreotide group (77.98 +/- 33.13) and the control group (75.98 +/- 30.99) respectively. The incidence of pancreatitis in the QYD, octreotide, and the control group was 2.6%, 0 and 11.4%, that of hyperamylasemia in them 28.2%, 21.4%, and 56.8%, respectively. The occurrence rate of hyperamylasemia was lower in the QYD group and the octreotide group than in the control group (P < 0.05).
CONCLUSIONQYD could lower CRP and up-regulate IL-10 level, restrain the inflammation reaction and reduce the blood amylase level in the post-ERCP period, thus reducing the incidence of hyperamylasemia.
Adolescent ; Adult ; Amylases ; blood ; C-Reactive Protein ; analysis ; Cholangiopancreatography, Endoscopic Retrograde ; adverse effects ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Hyperamylasemia ; etiology ; prevention & control ; Interleukin-10 ; blood ; Male ; Middle Aged ; Octreotide ; therapeutic use ; Pancreatitis ; etiology ; prevention & control ; Young Adult

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