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AstragalosideⅣplays a role in reducing radiation-induced liver inflammation in mice by inhibiting thioredoxin-interacting protein/nod-like receptor protein 3 signaling pathway

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Journal of Traditional Chinese Medicine 2023年第1期43卷 87-94页

作者： DING Yanping DONG Xiaoqing MA Yifan CHEN Lili ZHOU Jie LI Xinyan SHAO Baoping College of Life Science Northwest Normal UniversityLanzhou 730000China College of Life Science Lanzhou UniversityLanzhou 730000China

OBJECTIVE:To investigate the efficacy of Astragaloside IV(AS-IV)on radiation-induced liver inflammation in mice.METHODS:The mice were divided into normal group,dimethyl sulfoxide solvent group,irradiation group(IR),irradiation+AS-IV(20 mg/kg)group(IR+AS-20)and irradiation+AS-IV(40 mg/kg)group(IR+AS-40).One month after intraperitoneal injection of AS-IV,the mice were irradiated with 8Gry Co60γ,the blood was collected for biochemical analysis,and the liver was collected for hematoxylin-eosin staining,immunofluorescence and electron microscopic observation,oxidative stress,and Western blot analysis.RESULTS:The AS-IV treatment significantly ameliorated the pathological morphology of liver and reduced the alanine aminotransferase and aspertate aminotransferase levels in serum induced by radiation;AS-IV treatment also significantly reduced the expression of inflammatory factors tumor necrosis factor alpha and interleukin 6 and antagonized malonaldehyde content and superoxide dismutase activity in liver caused by radiation;in addition,AS-IV treatment can significantly inhibited the positive expression of thioredoxin-interacting protein(TXNIP)and nod-like receptor protein 3(nlrP3)inflammasome in liver tissue after radiation;The expression of TXNIP,nlrP3 inflammasome,apoptosisassociated speck-like protein containing a CARD,cysteinyl aspartate-specific proteinase 1 and interleukin 1beta in the AS-IV prevention group decreased significantly compared to the radiation group.CONCLUSIONS:These findings suggested that Co60γradiation can cause structural and functional damage to the liver,which may be related to the nlrP3 mediated inflammatory pathway;AS-IV may play a protective role by inhibiting the TXNIP/nlrP3 inflammasome signaling pathway in the radiation-induced liver injury model.

关键词： radiation,ionizing astragalosideⅣ liver inflammation nlr family,pyrin domain-containing 3 protein thioredoxin-interacting protein

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Ginsenoside Rb1 Reduces D-GalN/LPS-induced Acute Liver Injury by Regulating TLR4/NF-κB Signaling and nlrP3 Inflammasome

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Journal of Clinical and Translational Hepatology 2022年第3期10卷 474-485页

作者： Yimei Liu Ninghua Liu Yujing Liu Hongyu He Zhe Luo Wenjun Liu Nan Song Minjie Ju Department of Critical Care Medicine Zhongshan Hospital of Fudan UniversityShanghaiChina Department of Facial Plastic and Reconstructive Surgery Eye&ENT Hospital of Fudan UniversityShanghaiChina Department of Nursing Zhongshan Hospital of Fudan UniversityShanghaiChina

Background and Aims:The effect of ginsenoside Rb1 on D-galactosamine(D-GalN)/lipopolysaccharide(LPS)-induced acute liver injury(ALI)is unknown.The aim of this study was to evaluate the effect of ginsenoside Rb1 on ALI and its underlying mechanisms.Methods:Mice were pretreated with ginsenoside Rb1 by intraperitoneal injection for 3 days before D-GalN/LPS treatment,to induce ALI.The survival rate was monitored every hour for 24 h,and serum biochemical parameters,hepatic index and histopathological analysis were evaluated to measure the degree of liver injury.ELISA was used to detect oxidative stress and inflammatory cytokines in hepatic tissue and serum.Immunohistochemistry staining,RT-PCR and western blotting were performed to evaluate the expression of toll-like receptor 4(TLR4),nuclear factorkappa B(NF-κB),and nlr family,pyrin domain-containing 3 protein(nlrP3)in liver tissue and Kupffer cells(KCs).Results:Ginsenoside Rb1 improved survival with D-GalN/LPS-induced ALI by up to 80%,significantly ameliorated the increased alanine and aspartate transaminase,restored the hepatic pathological changes and reduced the levels of oxidative stress and inflammatory cytokines altered by D-GalN/LPS.Compared to the control group,the KCs were increased in the D-GalN/LPS groups but did not increase significantly with Rb1 pretreatment.D-GalN/LPS could upregulate while Rb1 pretreatment could downregulate the expression of interleukin(IL)-1β,IL-18,nlrP3,apoptosis associated specklike protein containing CARD(ASC)and caspase-1 in isolated KCs.Furthermore,ginsenoside Rb1 inhibited activation of the TLR4/NF-κB signaling pathway and nlrP3 inflammasome induced by D-GalN/LPS administration.Conclusions:Ginsenoside Rb1 protects mice against D-GalN/LPS-induced ALI by attenuating oxidative stress and the inflammatory response through the TLR4/NF-κB signaling pathway and nlrP3 inflammasome activation.

关键词： Ginsenosides Chemical and drug induced liver injury Toll-like receptor 4 nlr family,pyrin domain-containing 3 protein

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Reduning plus ribavirin display synergistic activity against severe pneumonia induced by H1N1 influenza A virus in mice

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Journal of Traditional Chinese Medicine 2020年第5期40卷 803-811页

作者： Chen Weitao Ma Yuexia Zhang Hong Guo Yali Guan Mengyue Wang Yuguang Department of Respiratory Medicine Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing 100010China Department of Respiratory Medicine Fangshan HospitalBeijing University of Chinese MedicineBeijing 102400China Department of Internal Medicine Fangshan HospitalBeijing University of Chinese MedicineBeijing 102400China

OBJECTIVE:To investigate synergistic effect of Reduning(RDN)injection plus ribavirin against severe pneumonia induced by H1 N1 influenza A virus in mice.METHODS:We established a mouse model of severe pneumonia induced by influenza A virus by infecting Balb/c mice with CA07 virus.We randomly assigned the infected mice into four groups,and treated them with normal saline(NS group),RDN(injection,86.6 mg/kg),ribavirin(injection,66.6 mg/kg)or double Ribavirin plus RDN group,the same dosage as used in the single treatments)for 5 d.Lung index and lung pathology were recorded or calculated in terms of the curative effective.Cytokines,NOD-like receptor family pyrin domain containing 3(nlrP3)inflammasome related protein including caspase-associated recruitment domain(CARD)domain Apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1 and NOD-like receptor family,pyrin domain containing 3(nlrP3),and reactive oxygen species were simultaneously investigated.RESULTS:RDN plus ribavirin treatment,not RDN or ribavirin alone,provided a significant survival benefit to the influenza A virus-infected mice.The combination treatment protected the mice against severe influenza infection by attenuating the severe lung injury.The combined treatment also reduced the viral titers in mouse lungs and lung index,downregulated their immunocytokine levels,including IL-1βand IL-18,and down regulated the nlrP3,especially the transcription and translation of caspase-1.Meanwhile NS group had significantly higher reactive oxygen species(ROS)expression which could was dramatically reduced by the treatment of RDN plus ribavirin.CONCLUSION:Our study showed that RDN combined with ribavirin could protect the mice,and reduce the lung immunopathologic damage caused by severe influenza pneumonia.The mechanism could be that it reduced ROS produce and inhibited nlrP3 inflammasome activation so that mainly lower the downstream inflammatory cytokines IL-1βand IL-18.

关键词： Influenza A Virus,H1N1 Subtype Pneumonia nlr family,pyrin domain-containing 3 protein Inflammasomes Ribavirin Reduning

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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 involved.METHODS: 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 measured.Liver 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 assay.RESULTS: 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 nlrP3, ASC, caspase-1, IL-1β, and IL-6(all P 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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Qingre Jianpi decoction(清热健脾汤)attenuates inflammatory responses by suppressing NOD-like receptor family pyrin domain-containing 3 inflammasome activation in dextran sulfate sodium-induced colitis mice

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Journal of Traditional Chinese Medicine 2021年第1期41卷 68-78页

作者： ZHANG Jiayan KANG Xiuhong SUN Mengyun ZHANG Shengsheng Department of Digestive System Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical UniversityBeijing 100010China Department of Digestive system Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical UniversityBeijing 100010China

OBJECTIVE:To investigate the effects of Qingre Jianpi decoction(清热健脾汤,QRJPD)on dextran sulfate sodium(DSS)-induced colitis mice and explore its mechanism.METHODS:All mice were randomly divided into six groups.Weight changes,disease activity index values,and histological damage were detected.Inflammatory cytokines and immune cell infiltration were measured using enzyme-linked immunosorbent assays(ELISA)and immunohistochemistry(IHC)method.The key protein expression levels of the NOD-like receptor family pyrin domain-containing 3(nlrP3)inflammasome were detected by western blot analysis,IHC,and quantitative reverse transcription polymerase chain reaction.RESULTS:QRJPD played an anti-inflammatory role in the treatment of ulcerative colitis(UC),reduced the secretion of inflammatory cytokines,and inhibited the inflammatory infiltration of immune cells by suppressing DSS-induced activation of the nlrP3 inflammasome.CONCLUSION:QRJPD exerts protective effects by inhibiting DSS-induced nlrP3 inflammasome activation.

关键词： Colitis,ulcerative anti-inflammatory agents nlr family,pyrin domain-containing 3 protein inflammasomes

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