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Ethyl Lithospermate Reduces Lipopolysaccharide-Induced Inflammation through Inhibiting NF-κB and STAT3 Pathways in RAW 264.7 Cells and Zebrafish

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Chinese Journal of Integrative Medicine 2023年第12期29卷 1111-1120页

作者： ZHOU Chun-hong YANG Hua ZOU Li-fang LIU Di-fa YU Lin-zhong CAO Hui-hui DENG Li-e WANG Zhang-wei LU Zi-bin LIU Jun-shan Third Level Research Laboratory of State Administration of Traditional Chinese Medicine Guangdong Provincial Key Laboratory of Chinese Medicine PharmaceuticsSchool of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou(510515)China Department of Pharmacy Zhujiang HospitalSouthern Medical UniversityGuangzhou(510282)China State Key Laboratory of Innovative Natural Medicine and Traditional Chinese Medicine Injections Jiangxi Qingfeng Pharmaceutical Co.Ltd.GanzhouJiangxi Province(341000)China Affiliated Dongguan People's Hospital Southern Medical UniversityDongguanGuangdong Province(523076)China

Objective:To explore the anti-inflammatory effects of ethyl lithospermate in Lipopolysaccharide(LPS)-stimulated RAW 264.7 murine-derived macrophages and zebrafish,and its underlying mechanisms.Methods:3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide(MTT)assays were performed to investigate the toxicity of ethyl lithospermate at different concentrations(12.5–100μmol/L)in RAW 264.7 cells.The cells were stimulated with LPS(100 ng/mL)for 12 h to establish an inflammation model in vitro,the production of proinflammatory cytokines interleukin(IL)-6 and tumor necrosis factorα(TNF-α)were assessed by enzyme linked immunosorbent assay(ELISA).Western blot was used to ascertain the protein expressions of signal transducer and activator of transcription 3(STAT3),nuclear factor kappa B(NF-κB)p65,phospho-STAT3(p-STAT3,Tyr705),inhibitor of NF-κB(IκB)α,and phospho-IκBα(p-IκBα,Ser32),and confocal imaging was used to identify the nuclear translocation of NF-κB p65 and p-STAT3(Tyr705).Additionally,the yolk sacs of zebrafish(3 days post fertilization)were injected with 2 nL LPS(0.5 mg/mL)to induce an inflammation model in vivo.Survival analysis,hematoxylin-eosin(HE)staining,observation of neutrophil migration,and quantitative real-time polymerase chain reaction(qR T-PCR)were used to further study the anti-inflammatory effects of ethyl lithospermate and its probable mechanisms in vivo.Results:The non-toxic concentrations of ethyl lithospermate have been found to range from 12.5 to 100μmol/L.Ethyl lithospermate inhibited the release of IL-6 and TNF-α(P<0.05 or P<0.01),decreased IκBαdegradation and phosphorylation(P<0.05)as well as the nuclear translocation of NF-κB p65 and p-STAT3(Tyr705)in LPS-induced RAW 264.7 cells(P<0.01).Ethyl lithospermate also decreased inflammatory cells infiltration and neutrophil migration while increasing the survival rate of LPS-stimulated zebrafish(P<0.05 or P<0.01).In addition,ethyl lithospermate also inhibited the mR NA expression levels of of IL-6,TNF-α,IκBα,STAT3,and NF-κB in LPS-stimulated

关键词： ethyl lithospermate anti-inflammation nuclear factor kappa B signal transducer and activator of transcription 3 Lipopolysaccharide zebrafish

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Anti-oxidant and Anti-inflammatory Effects of Ethanol Extract from Polygala sibirica L.var megalopha Fr.on Lipopolysaccharide-Stimulated RAW264.7 Cells

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中国结合医学杂志:英文版 2023年第10期29卷 905-913页

作者： YANG Cheng-liu WANG Shi-bo HE Wen-ping LIU Jin-juan Key Laboratory of Biotechnology for Medicinal Plants of Jiangsu Province School of Life ScienceJiangsu Normal UniversityXuzhouJiangsu Province221116China

Objective To investigate the anti-oxidant and anti-inflammatory effects of ethanol extract of Polygala sibirica L.var megalopha Fr.(EEP)on RAW264.7 mouse macrophages.Methods RAW264.7 cells were pretreated with 0–200µg/mL EEP or vehicle for 2 h prior to exposure to 1µg/mL Lipopolysaccharide(LPS)for 24 h.Nitric oxide(NO)and prostaglandin(PGE2)production were determined by Griess reagent and enzyme-linked immunosorbent assay(ELISA),respectively.The mRNA levels of inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2),tumor necrosis factorα(TNF-α),interleukin-1beta(IL-1β),and IL-6 were determined using reverse transcription polymerase chain reaction(RT-PCR).Western blot assay was used to determine the protein expressions of iNOS,COX-2,phosphorylation of extracellular regulated protein kinases(ERK1/2),c-Jun N-terminal kinase(JNK),inhibitory subunit of nuclear factor Kappa B alpha(IκB-α)and p38.Immunofluorescence was used to observe the nuclear expression of nuclear factor-κB p65(NF-κB p65).Additionally,the anti-oxidant potential of EEP was evaluated by reactive oxygen species(ROS)production and the activities of catalase(CAT)and superoxide dismutase(SOD).The 2,2-diphenyl-1-picrylhydrazyl(DPPH),hydroxyl(OH),superoxide anion(O2−)radical and nitrite scavenging activity were also measured.Results The total polyphenol and flavonoid contents of EEP were 23.50±2.16 mg gallic acid equivalent/100 g and 43.78±3.81 mg rutin equivalent/100 g.With EEP treatment(100 and 150µg/mL),there was a notable decrease in NO and PGE2 production induced by LPS in RAW264.7 cells by downregulation of iNOS and COX-2 mRNA and protein expressions(P<0.01 or P<0.05).Furthermore,with EEP treatment(150µg/mL),there was a decrease in the mRNA expression levels of TNF-α,IL-1βand IL-6,as well as in the phosphorylation of ERK,JNK and p38 mitogen-activated protein kinase(MAPK,P<0.01 or P<0.05),by blocking the nuclear translocation of NF-κB p65 in LPS-stimulated cells.In addition,EEP(100 and 150µg/mL)led to an increase in the anti-oxidant enzymes activ

关键词： Polygala sibirica L.var megalopha Fr. anti-inflammatory anti-oxidant RAW264.7 cells Lipopolysaccharide Chinese medicine

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Leaky Gut Plays a Critical Role in the Pathophysiology of Autism in Mice by Activating the Lipopolysaccharide‑Mediated Toll‑Like Receptor 4-Myeloid Differentiation Factor 88-Nuclear Factor Kappa B Signaling Pathway

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Neuroscience Bulletin 2023年第6期39卷 911-928页

作者： Fang Li Haoran Ke Siqi Wang Wei Mao Cexiong Fu Xi Chen Qingqing Fu Xiaori Qin Yonghua Huang Bidan Li Shibing Li Jingying Xing Minhui Wang Wenlin Deng Department of Gastroenterology Gastroenterology Endoscopy CenterHainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Hepatology Unit Department of Infectious DiseasesNanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Gastroenterology First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Medical UniversityGuangzhou 510120China Department of Hepatopancreatobiliary Surgery Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Otolaryngology‑Head and Neck Surgery Hospital of Hainan ProvinceDepartment of OtorhinolaryngologyHead and Neck SurgeryHainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Department of Radiology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Department of Pediatric Surgery Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Department of Gastroenterology Hainan General HospitalHainan Affiliated Hospital of Hainan Medical UniversityHaikou 570311China Department of Nephrology Department of NephrologyHainan Affiliated Hospital of Hainan Medical CollegeHainan General HospitalHaikou 570311China Department of Pediatrics The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510655China

Increased intestinal barrier permeability,leaky gut,has been reported in patients with autism.However,its contribution to the development of autism has not been determined.We selected dextran sulfate sodium(DSS)to disrupt and metformin to repair the intestinal barrier in BTBR T+tf/J autistic mice to test this hypothesis.DSS treatment resulted in a decreased affinity for social proximity;however,autistic behaviors in mice were improved after the administration of metformin.We found an increased affinity for social proximity/social memory and decreased repetitive and anxiety-related behaviors.The concentration of Lipopolysaccharides in blood decreased after the administration of metformin.The expression levels of the key molecules in the toll-like receptor 4(TLR4)–myeloid differentiation factor 88(MyD88)–nuclear factor kappa B(NF-κB)pathway and their downstream inflammatory cytokines in the cerebral cortex were both repressed.Thus,“leaky gut”could be a trigger for the development of autism via activation of the Lipopolysaccharide-mediated TLR4–MyD88–NF-κB pathway.

关键词： Autism Gut Lipopolysaccharide Toll-like receptor 4 Metformin

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Rice bran oil supplementation protects swine weanlings against diarrhea and Lipopolysaccharide challenge

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第5期24卷 430-441页

作者： Juncheng HUANG Wenxia QIN Baoyang XU Haihui SUN Fanghua JING Yunzheng XU Jianan ZHAO Yuwen CHEN Libao MA Xianghua YAN State Key Laboratory of Agricultural Microbiology Hubei Hongshan LaboratoryFrontiers Science Center for Animal Breeding and Sustainable ProductionCollege of Animal Sciences and TechnologyHuazhong Agricultural UniversityWuhan 430070China The Cooperative Innovation Center for Sustainable Pig Production Wuhan 430070China Hubei Provincial Engineering Laboratory for Pig Precision Feeding and Feed Safety Wuhan 430070China Yichun Dahaigui Life Science Co. Ltd.Yichun 336000China

Early weaned piglets suffer from oxidative stress and enteral infection,which usually results in gut microbial dysbiosis,serve diarrhea,and even death.Rice bran oil(RBO),a polyphenol-enriched by-product of rice processing,has been shown to have antioxidant and anti-inflammatory properties both in vivo and in vitro.Here,we ascertained the proper RBO supplementation level,and subsequently determined its effects on Lipopolysaccharide(LPS)-induced intestinal dysfunction in weaned piglets.A total of 168 piglets were randomly allocated into four groups of seven replicates(42 piglets each group,(21±1)d of age,body weight(7.60±0.04)kg,and half males and half females)and were given basal diet(Ctrl)or basal diet supplemented with 0.01%(mass fraction)RBO(RBO1),0.02%RBO(RBO2),or 0.03%RBO(RBO3)for 21 d.Then,seven piglets from the Ctrl and the RBO were treated with LPS(100μg/kg body weight(BW))as LPS group and RBO+LPS group,respectively.Meanwhile,seven piglets from the Ctrl were treated with the saline vehicle(Ctrl group).Four hours later,all treated piglets were sacrificed for taking samples of plasma,jejunum tissues,and feces.The results showed that 0.02%was the optimal dose of dietary RBO supplementation based on diarrhea,average daily gain,and average daily feed intake indices in early weaning piglets.Furthermore,RBO protected piglets against LPS-induced jejunal epithelium damage,which was indicated by the increases in villus height,villus height/crypt depth ratio,and Claudin-1 levels,as well as a decreased level of jejunal epithelium apoptosis.RBO also improved the antioxidant ability of LPS-challenged piglets,which was indicated by the elevated concentrations of catalase and superoxide dismutase,and increased total antioxidant capacity,as well as the decreased concentrations of diamine oxidase and malondialdehyde in plasma.Meanwhile,RBO improved the immune function of LPS-challenged weaned piglets,which was indicated by elevated immunoglobulin A(IgA),IgM,β-defensin-1,and lysozyme levels in the plasma.In addition,RBO supp

关键词： Rice bran oil Gut microbiota Weaned piglets Oxidative stress Lipopolysaccharide

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Yeast hydrolysate attenuates Lipopolysaccharide-induced inflammatory responses and intestinal barrier damage in weaned piglets

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Journal of Animal Science and Biotechnology 2023年第4期14卷 1569-1583页

作者： Runqi Fu Chan Liang Daiwen Chen Gang Tian Ping Zheng Jun He Jie Yu Xiangbing Mao Yuheng Luo Junqiu Luo Bing Yu Key Laboratory of Animal Disease-Resistance Nutrition Ministry of EducationMinistry of Agriculture and Rural AffairsKey Laboratory of Sichuan ProvinceChengdu 611130China Institute of Animal Nutrition Sichuan Agricultural UniversityChengdu 611130SichuanChina

Background Intestinal inflammation is the main risk factor causing intestinal barrier dysfunction and Lipopolysaccharide(LPS)can trigger inflammatory responses in various eukaryotic species.Yeast hydrolysate(YH)possesses multibiological effects and is received remarkable attention as a functional ingredient for improving growth performance and promoting health in animals.However,there is still inconclusive on the protective effects of dietary YH supplementation on intestinal barrier of piglets.This study was conducted to investigate the attenuate effects of YH supplementation on inflammatory responses and intestinal barrier injury in piglets challenged with LPS.Methods Twenty-four piglets(with an average body weight of 7.42±0.34 kg)weaned at 21 days of age were randomly assigned to one of two dietary treatments(12 replications with one pig per pen):a basal diet or a basal diet containing YH(5 g/kg).On the 22nd d,6 piglets in each treatment were intraperitoneally injected with LPS at 150μg/kg BW,and the others were injected with the same amount of sterile normal saline.Four hours later,blood samples of each piglet were collected and then piglets were euthanized.Results Dietary YH supplementation increased average daily feed intake and average daily gain(PLipopolysaccharide(LPS)injection induced systemic inflammatory ref serum concentrations of haptoglobin(HP),adrenocorticotropic hormone(ACTH),cortisol,and interleukin-1β(IL-1β).Furthermore,LPS challenge resulted in inflammatory intestinal damage,by up-regulation of the protein or mRNA abundances of tumor necrosis factor-α(TNF-α),IL-1β,toll-like receptors 4(TLR4)and phosphor-nuclear factor-κB-p65(p-NFκB-p65)(P<0.01),and down-regulation of the jejunal villus height,the protein and mRNA abundances of zonula occludens-1(ZO-1)and occludin(OCC;P<0.05)in jejunal mucosa.Dietary YH supplementation decreased the impaired effects of ACTH,cortisol,HP,IL-1βand diamine oxidas

关键词： Inflammatory response Intestinal barrier Lipopolysaccharide Piglets Yeast hydrolysate

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Lipopolysaccharide induced intestinal epithelial injury:a novel organoids-based model for sepsis in vitro

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Chinese Medical Journal 2022年第18期135卷 2232-2239页

作者： Sisi Huang Sheng Zhang Limin Chen Xiaojun Pan Zhenliang Wen Yizhu Chen Lidi Zhang Jiao Liu Dechang Chen Department of Critical Care Medicine Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200020China Department of Critical Care Medicine Ruijin Hospital NorthShanghai Jiao Tong University School of MedicineShanghai 201801China

Background: Advances in organoid culture technology have provided a greater understanding of disease pathogenesis, which has been rarely studied in sepsis before. We aim to establish a suitable organoids-based intestinal injury model for sepsis.Methods: Stable passaged organoids were constructed and pre-treated with Lipopolysaccharide (LPS) to mimic sepsis-induced intestinal injury. The LPS-induced sepsis model was used as a reference. We used quantitative real-time polymerase chain reaction to evaluate the RNA levels of inflammatory factors and antimicrobial peptides. Enzyme-linked immunosorbent assay was used to evaluate the protein levels, hematoxylin and eosin staining was used to evaluate the pathology of the small intestine of mice, and immunohistochemistry and immunofluorescence were used to evaluate the intestinal epithelial barrier function. Perkin Elmer OperettaTM was used to obtain high-resolution images of three-dimensional organoids.Results: An LPS concentration >150 μg/mL after 24 h was identified to cause organoid growth restriction. The fluorescence intensity of zonula occludens-1 and occludins at LPS concentrations >100 μg/mL decreased significantly after 24 h. After LPS stimulation for 8 h, the RNA expression levels of interleukin (IL)-1α, tumor necrosis factor alpha, granulocyte-macrophage colony-stimulating factor, IL-6, and regenerating islet-derived protein 3 alpha, beta, and gamma increased. These results resembled those of intestinal epithelial layer alterations in a mouse sepsis model. For IL-10, the RNA expression level increased only when the LPS level >200 μg/mL for 24 h.Conclusions: This study provides the primary intestinalin vitro model to study the effects of LPS-induced intestinal injury resembling sepsis. This model provides a platform for immune associated mechanism exploration and effective drug screening.

关键词： Organoids Sepsis Lipopolysaccharide Barrier function Inflammatory factors

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Early-life galacto-oligosaccharides supplementation alleviates the small intestinal oxidative stress and dysfunction of Lipopolysaccharide-challenged suckling piglets

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Journal of Animal Science and Biotechnology 2022年第5期13卷 1543-1556页

作者： Shiyi Tian Jue Wang Ren Gao Jing Wang Weiyun Zhu Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal HealthNational Center for International Research on Animal Gut NutritionNational Experimental Teaching Demonstration Center of Animal ScienceCollege of Animal Science and TechnologyNanjing Agricultural UniversityNanjing 210095China

Background:Galacto-oligosaccharides(GOS)are non-digestible food ingredients that promote the growth of beneficial bacteria in the gut.This study investigated the protective effect of the early-life GOS supplement on the piglets’gut function against the oxidative stress induced by Lipopolysaccharide(LPS)-challenge.Methods:Eighteen neonatal piglets were assigned to three groups including CON,LPS and LPS+GOS groups.The piglets in CON group and LPS group received physiological saline,while those in LPS+GOS group received GOS solution for 13 d after birth.On d 14,the piglets in LPS group and LPS+GOS group were injected with LPS solutions,while the piglets in CON group were injected with the same volume of physiological saline.Results:The results showed that the early-life GOS supplement blocked the LPS-induced reactive oxygen species(ROS)secretion,malondialdehyde(MDA)production and the increase of pro-apoptotic factor expression.Meanwhile,the early-life GOS supplement improved the activities of antioxidant enzymes,disaccharidase enzymes activities,and digestive enzymes activities,and increased the mRNA abundance of the gene related to nutrient digestion and absorption and the relative protein expression of tight junction.The study also showed that the early-life GOS supplement improved the expression of Hemeoxygenase-1(HO-1)and NAD(P)H/quinone acceptor oxidoreductase-1(NQO-1),and activated the AMP-activated protein kinase(AMPK).Conclusions:These results suggested that GOS enhanced the gut function,reduced the ROS production and proapoptotic factors gene expression,and activated the AMPK signaling pathway in LPS-challenged piglets.

关键词： Early-life Galacto-oligosaccharides Lipopolysaccharide Oxidative stress Suckling piglets

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Lipopolysaccharide-induced Trigeminal Ganglion Nerve Fiber Damage is Associated with Autophagy Inhibition

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当代医学科学(英文) 2023年第3期43卷 489-495页

作者： Yong LI Jing LI Sheng-sheng WEI Jing DU Refractive Surgery Center Shaanxi Eye HospitalXi'an People's Hospital(Xi'an Fourth Hospital)Affiliated Guangren HospitalSchool of MedicineXi'an Jiaotong UniversityXi'an 710004China

Objective This study aimed to determine whether Lipopolysaccharide(LPS)induces the loss of corneal nerve fibers in cultured trigeminal ganglion(TG)cells,and the underlying mechanism of LPS-induced TG neurite damage.Methods TG neurons were isolated from C57BL/6 mice,and the cell viability and purity were maintained for up to 7 days.Then,they were treated with LPS(1µg/mL)or the autophagy regulator(autophibib and rapamycin)alone or in combination for 48 h,and the length of neurites in TG cells was examined by the immunofluorescence staining of the neuron-specific proteinβ3-tubulin.Afterwards,the molecular mechanisms by which LPS induces TG neuron damage were explored.Results The immunofluorescence staining revealed that the average length of neurites in TG cells significantly decreased after LPS treatment.Importantly,LPS induced the impairment of autophagic flux in TG cells,which was evidenced by the increase in the accumulation of LC3 and p62 proteins.The pharmacological inhibition of autophagy by autophinib dramatically reduced the length of TG neurites.However,the rapamycin-induced activation of autophagy significantly lessened the effect of LPS on the degeneration of TG neurites.Conclusion LPS-induced autophagy inhibition contributes to the loss of TG neurites.

关键词： Lipopolysaccharide autophagy trigeminal ganglion neurons

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Effect of dual targeting procyanidins nanoparticles on metabolomics of Lipopolysaccharide-stimulated inflammatory macrophages

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Food Science and Human Wellness 2023年第6期12卷 2252-2262页

作者： Shanshan Tie Lijuan Zhang Bin Li Shanghua Xing Haitao Wang Yannan Chen Weina Cui Shaobin Gu Mingqian Tan Academy of Food Interdisciplinary Science School of Food Science and TechnologyDalian Polytechnic UniversityDalian 116034China College of Food and Bioengineering Henan University of Science and TechnologyLuoyang 471023China College of Food Science Shenyang Agricultural UniversityNational R&D Professional Center for Berry ProcessingShenyang 110866China

Inflammation plays an important role in the occurrence and development of many inflammatory diseases.The purpose of this study was to evaluate the anti-inflammatory effect and metabolic behavior of the dual targeting procyanidins(PC)nanoparticles on Lipopolysaccharide(LPS)-stimulated inflammatory macrophages by metabolomics method.The double-targeting PC nanoparticles could specifi cally target both the CD44 receptor and mitochondria,while the single targeting PC-loaded nanoparticles that could target the CD44 receptor on the surface of macrophages.The double-targeting PC nanoparticles had better inhibitory effect than single-targeting PC nanoparticles on the leakage of lactate dehydrogenase and reactive oxygen species overexpression induced by LPS.Amino acid metabolism,energy metabolism and purine metabolism were disordered in LPS-treated group,and metabolic pathway analysis indicated that the double-targeting PC nanoparticles reversed some of LPS impacts.The changes of these potential biomarkers and their corresponding pathways are helpful to further understand the mechanism of PC nanoparticles in alleviating inflammation,and promote their application in nutrition intervention.

关键词： Procyanidins nanoparticles Metabolomics Inflammation Macrophages Lipopolysaccharide

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Minocycline Activates the Nucleus of the Solitary Tract- Associated Network to Alleviate Lipopolysaccharide-Induced Neuroinflammation

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Chinese Medical Sciences Journal 2022年第1期37卷 1-14页

作者： Jianbo Xiu Lanlan Li Qi Xu State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100005China Neuroscience Center Chinese Academy of Medical SciencesBeijing 100005China

Objective To examine the neuroanatomical substrates underlying the effects of minocycline in alleviating Lipopolysaccharide(LPS)-induced neuroinflammation.Methods Forty C57BL/6 male mice were randomly and equally divided into eight groups.Over three conse-cutive days,saline was administered to four groups of mice and minocycline to the other four groups.Immediately after the administration of saline or minocycline on the third day,two groups of mice were additionally injected with saline and the other two groups were injected with LPS.Six or 24 hours after the last injection,mice were sacrificed and the brains were removed.Immunohistochemical staining across the whole brain was performed to detect microglia activation via Iba1 and neuronal activation via c-Fos.Morphology of microglia and the number of c-Fo-positive neurons were analyzed by Image-Pro Premier 3D.One-way ANOVA and Fisher’s least-significant differences were employed for statistical analyses.Results Minocycline alleviated LPS-induced neuroinflammation as evidenced by reduced activation of microglia in multiple brain regions,including the shell part of the nucleus accumbens(Acbs),paraventricular nucleus(PVN)of the hypothalamus,central nucleus of the amygdala(CeA),locus coeruleus(LC),and nucleus tractus solitarius(NTS).Minocycline significantly increased the number of c-Fo-positive neurons in NTS and area postrema(AP)after LPS treatment.Furthermore,in NTS-associated brain areas,including LC,lateral parabrachial nucleus(LPB),periaqueductal gray(PAG),dorsal raphe nucleus(DR),amygdala,PVN,and bed nucleus of the stria terminali(BNST),minocycline also significantly increased the number of c-Fo-positive neurons after LPS administration.Conclusion Minocycline alleviates LPS-induced neuroinflammation in multiple brain regions,possibly due to increased activation of neurons in the NTS-associated network.

关键词： neuroinflammation Lipopolysaccharide depression nucleus tractus solitaries microglia

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