AIM: To investigate the effect of oridonin on nuclear transcription factors and to study the relationship between biological behavior and inflammatory factors in human pancreatic cancer (BxPC-3) cells.
Inflammatory bowel disease(IBD)is a chronic inflammatory lesion of the intestine,mainly manifested by infiltration of intestinal inflammatory cells and imbalance of gut microbiota.Conventional treatments for IBD inclu...Inflammatory bowel disease(IBD)is a chronic inflammatory lesion of the intestine,mainly manifested by infiltration of intestinal inflammatory cells and imbalance of gut microbiota.Conventional treatments for IBD include antibiotics,immunosuppressive agents,5-aminosalicylic acid,steroids and surgery,which have high toxic side effects.Resveratrol is a natural polyphenol,and its various derivatives have anti-oxidation and anti-inflammatory properties.In this paper,we comprehensively review the mechanism of resveratrol and its derivates to alleviate IBD by improving intestinal barrier,regulating the unbalanced gut microbiota,and targeting various inflammatory signaling pathways.展开更多
The“longevity protein”SIRT5 could hold the key to delaying age-related muscle decline.A study led by researchers from the Institute of Zoology(IOZ)of the Chinese Academy of Sciences and Capital Medical University in...The“longevity protein”SIRT5 could hold the key to delaying age-related muscle decline.A study led by researchers from the Institute of Zoology(IOZ)of the Chinese Academy of Sciences and Capital Medical University in Beijing reveals that SIRT5 mitigates skeletal muscle aging by blocking pro-inflammatory pathways.Published in Nature Metabolism on March 14,2025,the work identifies SIRT5’s interaction with protein kinase TBK1 as critical to preserving muscle mass and function.展开更多
Inflammation represents a critical immune response triggered by cellular activities and inflammatory mediators following tissue damage.It plays a central role in the pathological progression of diverse diseases,includ...Inflammation represents a critical immune response triggered by cellular activities and inflammatory mediators following tissue damage.It plays a central role in the pathological progression of diverse diseases,including psychiatric disorders,cancer,and immunological conditions,rendering it an essential target for therapeutic intervention.Periodontitis,a prevalent oral inflammatory disease,is a leading cause of tooth loss and poses significant health challenges globally.Traditionally,inflammatory diseases such as periodontitis have been treated with systemic administration of synthetic chemicals.However,recent years have witnessed challenges,including drug resistance and microbial dysbiosis associated with these treatments.In contrast,natural products derived from Chinese medicine offer numerous benefits,such as high safety profiles,minimal side effects,innovative pharmacological mechanisms,ease of extraction,and multiple targets,rendering them viable alternatives to conventional antibiotics for treating inflammatory conditions.Numerous effective anti-inflammatory natural products have been identified in traditional Chinese medicine(TCM),including alkaloids,flavonoids,terpenoids,lignans,and other natural products that exhibit inhibitory effects on inflammation and are potential therapeutic agents.Several studies have confirmed the substantial anti-inflammatory and immunomodulatory properties of these compounds.This comprehensive review examines the literature on the anti-inflammatory effects of TCM-derived natural products from databases such as PubMed,Web of Science,and CNKI,focusing on terms like"inflammation","periodontitis","pharmacology",and"traditional Chinese medicine".The analysis systematically summarizes the molecular pharmacology,chemical composition,and biological activities of these compounds in inflammatory responses,alongside their mechanisms of action.This research seeks to deepen understanding of the mechanisms and biological activities of herbal extracts in managing inflammatory diseases,potentially leading to the development of promising new anti-inflammatory drug candidates.Future applications could extend to the treatment of various inflammatory conditions,including periodontitis.展开更多
Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive functi...Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive function of offspring are not yet fully understood.The present study classified institute of cancer research(ICR)mice into control and BDE-209 treatment groups,administering doses of 0 and 75 mg/(kg·day),respectively.After 50 days of exposure,normal female mice were co-housed with the male mice,and their male offspring were sacrificed at 2 and 12 months of age.Paternal BDE-209 exposure reduced both sperm quantity and quality in offspring.Furthermore,exposure to BDE-209 resulted in DNA damage and the upregulation of the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)DNA-sensing and inflammatory signaling pathways.The activation resulted in Z-DNA binding protein 1(ZBP1)binding to the mitochondrial antiviral signaling protein(MAVS),subsequently activating mitochondrial apoptosis in the testes.The activation of the cGAS-STING pathway inhibited mitophagy,leading to senescence in the testes of male offspring.In vitro studies indicated that the cGAS inhibitor RU320521(RU.521)effectively reversed the cGAS-STING pathway activation,alleviated the mitophagy inhibition,and decreased apoptosis and senescence in mouse spermatocyte line GC-2spd cells treated with BDE-209.The results showed that paternal BDE-209 exposure might disrupt spermatogenesis in mouse offspring by activating the cGAS-STING pathway and inhibiting mitophagy.This study provides essential data on the toxicity of BDE-209 to male reproduction and have important scientific and practical implications for maintaining biodiversity and population health in general.展开更多
Rheumatoid arthritis(RA)is one of the most common refractory diseases in the world,and traditional Chinese medicine Notopterygium(NE)has been used in the treatment of upper limb pain for a long time.NE can significant...Rheumatoid arthritis(RA)is one of the most common refractory diseases in the world,and traditional Chinese medicine Notopterygium(NE)has been used in the treatment of upper limb pain for a long time.NE can significantly reduce the expression of inflammatory pain target P2X3 receptor in rats with upper-limb arthritis.To verify the relationship between the mechanism of NE for“upper limb paralysis”and the P2X3 receptor-mediated PKC inflammatory response pathway,UPLC was taken to measure the exact medicinal substance of ethyl acetate from NE.Sprague Dawley rats were randomly divided into a blank group,a model group,a live-action group,and a positive group.The joint cavity was removed after 21 d.Moreover,a model group,a live group,and a positive group were also set up with RA-FLS cells in our in vitro study.The expressions of P2X3 and PKC inflammation pathway indicators were detected by Western blotting analysis.A P2X3 inhibitor(A-317491)acted on RA-FLS cells,and a model group and a positive group were set.Then the protein expression of PKC was detected.NE reduced the expressions of P2X3,Rab7,PKC,and NF-κB at the protein level in both systems.NE and P2X3 receptor antagonists reduced the expressions of key proteins in the PKC pathway in RA-FLS cells to similar extents,and their effects were not additive.NE could effectively improve the“forelimb pain”of RA rats,with a mechanism closely related to the P2X3/Rab7/PKC/NF-κB pathway.展开更多
MicroRNAs(miRNAs)are small non-coding RNA molecules that regulate post-transcriptional gene expression and contribute to all aspects of cellular function.We previously reported that the activities of several mitochond...MicroRNAs(miRNAs)are small non-coding RNA molecules that regulate post-transcriptional gene expression and contribute to all aspects of cellular function.We previously reported that the activities of several mitochondria-enriched miRNAs regulating inflammation(i.e.,miR-142-3p,miR-142-5p,and miR-146a)are altered in the hippocampus at 3–12 hours following a severe traumatic brain injury.In the present study,we investigated the temporal expression profile of these inflammatory miRNAs in mitochondria and cytosol fractions at more chronic post-injury times following severe controlled cortical impact injury in rats.In addition,several inflammatory genes were analyzed in the cytosol fractions.The analysis showed that while elevated levels were observed in cytoplasm,the mitochondria-enriched miRNAs,miR-142-3p and miR-142-5p continued to be significantly reduced in mitochondria from injured hippocampi for at least 3 days and returned to near normal levels at 7 days post-injury.Although not statistically significant,miR-146a also remained at reduced levels for up to 3 days following controlled cortical impact injury,and recovered by 7 days.In contrast,miRNAs that are not enriched in mitochondria,including miR-124a,miR-150,miR-19b,miR-155,and miR-223 were either increased or demonstrated no change in their levels in mitochondrial fractions for 7 days.The one exception was that miR-223 levels were reduced in mitochondria at 1 day following injury.No major alterations were observed in sham operated animals.This temporal pattern was unique to mitochondria-enriched miRNAs and correlated with injury-induced changes in mitochondrial bioenergetics as well as expression levels of several inflammatory markers.These observations suggested a potential compartmental re-distribution of the mitochondria-enriched inflammatory miRNAs and may reflect an intracellular mechanism by which specific miRNAs regulate injury-induced inflammatory signaling.To test this,we utilized a novel peptide-based nanoparticle strategy for in vitro and in vivo delivery of a miR-146a mimic as a potential therapeutic strategy for targeting nuclear factor-kappa B inflammatory modulators in the injured brain.Nanoparticle delivery of miR-146a to BV-2 or SH-SY5Y cells significantly reduced expression of TNF receptor-associated factor 6(TRAF6)and interleukin-1 receptor-associated kinase 1(IRAK1),two important modulators of the nuclear factor-kappa B(NF-κB)pro-inflammatory pathway.Moreover,injections of miR-146a containing nanoparticles into the brain immediately following controlled cortical impact injury significantly reduced hippocampal TNF receptor-associated factor 6 and interleukin-1 receptor-associated kinase 1 levels.Taken together,our studies demonstrate the subcellular alteration of inflammatory miRNAs after traumatic brain injury and establish proof of principle that nanoparticle delivery of miR-146a has therapeutic potential for modulating pro-inflammatory effectors in the injured brain.All of the studies performed were approved by the University of Kentucky Institutional Animal Care and Usage Committee(IACUC protocol#2014-1300)on August 17,2017.展开更多
Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent ye...Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.展开更多
Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.Howev...Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.展开更多
COVID-19,as a concern in the world,can lead to death with a wide range of symptoms.Coronavirus,like other viral diseases,leads to the activation of inflammatory responses such as triggering the cytokine cascade.During...COVID-19,as a concern in the world,can lead to death with a wide range of symptoms.Coronavirus,like other viral diseases,leads to the activation of inflammatory responses such as triggering the cytokine cascade.During the contact of the surface of the virus and its internal components with the human immune system,the path of expression and activation of cytokines begins.The body fights the virus through this operation and sometimes cell apoptosis.In the current review study,PubMed,Scopes,and Google Scholar were searched to provide information have shown the inflammasomes of COVID-19.In a review study,we examine the evidence that shows that COVID-19 activates inflammasomes;inflammasomes are cytosolic receptors that can identify microbial pathogens and endogenous signals resulting from stress or cell damage,including NLRP3(NLR Family Pyrin Domain Containing 3)type,NLRP4(NLR Family Pyrin Domain Containing 4),NLRP3.Through the activation of ASC and caspase 1,inflammasomes lead to the secretion of cytokines IL-1β(Interleukin-1 beta),IL-18(Interleukin-18),and IL6(Interleukin-6),TNF-α(Tumor Necrosis Factor-alpha).They can lead to the activation of inflammatory pathways.The results of this research can be useful in clarifying the relationship between the inflammatory pathways caused by the COVID-19 virus in people and the discovery of drugs in infected people.展开更多
As a classic noninvasive physiotherapy,photobiomodulation,also known as low-level laser therapy,is widely used for the treatment of many diseases and has anti-inflammatory and tissue repair effects.Photobiomodulation ...As a classic noninvasive physiotherapy,photobiomodulation,also known as low-level laser therapy,is widely used for the treatment of many diseases and has anti-inflammatory and tissue repair effects.Photobiomodulation has been shown to promote spinal cord injury repair.In our previous study,we found that 810 nm low-level laser therapy reduced the M1 polarization of macrophages and promoted motor function recovery.However,the mechanism underlying this inhibitory effect is not clear.In recent years,transcriptome sequencing analysis has played a critical role in elucidating the progression of diseases.Therefore,in this study,we performed M1 polarization on induced mouse bone marrow macrophages and applied low-level laser therapy.Our sequencing results showed the differential gene expression profile of photobiomodulation regulating macrophage polarization.We analyzed these genes using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.Networks of protein-protein interactions and competing RNA endogenous networks were constructed.We found that photobiomodulation inhibited STAT3 expression through increasing the expression of miR-330-5p,and that miR-330-5p binding to STAT3 inhibited STAT3 expression.Inducible nitric oxide synthase showed trends in changes similar to the changes in STAT3 expression.Finally,we treated a mouse model of spinal cord injury using photobiomodulation and confirmed that photobiomodulation reduced inducible nitric oxide synthase and STAT3 expression and promoted motor function recovery in spinal cord injury mice.These findings suggest that STAT3 may be a potential target of photobiomodulation,and the miR-330-5p/STAT3 pathway is a possible mechanism by which photobiomodulation has its biological effects.展开更多
Objective： To observe the effects of red yeast rice（RYR） on blood lipid levels, aortic atherosclerosis（AS）, and plaque stability in apolipoprotein E gene knockout（Apo E-/-） mice. Methods： Twentyfour Apo E-/-mi...Objective： To observe the effects of red yeast rice（RYR） on blood lipid levels, aortic atherosclerosis（AS）, and plaque stability in apolipoprotein E gene knockout（Apo E-/-） mice. Methods： Twentyfour Apo E-/-mice were fed with a high-fat diet starting from 6 weeks of age. Mice were randomized into three groups（n = 8 in each group）： model group（Apo E-/-group）, RYR group（Apo E-/-＋ RYR group）, and simvastatin group（Apo E-/-＋ simvastatin group）. Eight 6-week-old C57BL/6 mice were assigned as the control group and fed with a basic diet. After 36 weeks, plasma lipids and inflammatory factors were measured. Aortic atherosclerotic lesions by microscope, scanning electron microscope and transmission electron microscope were observed. Plasma levels of interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） were measured with enzymelinked immunosorbent assay. The level of high sensitivity C-reaction protein（Hs-CRP） was detected by the scattering immunoturbidimetric assay. Protein expression of matrix metalloproteinase-9（MMP-9） and nuclear factor κB（NF-κB） in aorta were tested by immunohistochemistry. Results： Compared with the model group, treatment with RYR significantly decreased the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, lipoprotein（a）, and apolipoprotein B100 in Apo E-/-mice（P〈0.01）. Compared with the model group, treatment with RYR decreased the levels of Hs-CRP, IL-6, and TNF-α（P〈0.01）. RYR also reduced the protein levels of NF-κB and MMP-9 of the aorta. Conclusions： RYR has the anti-atherosclerotic and stabilizing unstable plaque effects. The mechanism might be related to the inflammatory signaling pathways.展开更多
Gastric cancer is closely related to the stomach microbiota,especially Helicobacter pylori.Numerous reports and clinical studies have shown that microbial behavior in the stomach may lead to pathological changes in th...Gastric cancer is closely related to the stomach microbiota,especially Helicobacter pylori.Numerous reports and clinical studies have shown that microbial behavior in the stomach may lead to pathological changes in the gastrointestinal tract of the host,which ultimately leads to the production and development of gastric cancer.This review outlines the major pathogenic processes of Helicobacter pylori in the stomach,specifically focusing on Cag A,Vac A,inflammatory pathways and oxidative stress.In addition,we describe the effects of some non-Helicobacter pylori factors,such as other microbiota,alcohol,and tobacco,on the carcinogenesis induced by Helicobacter pylori.The effects of family history are also taken into account.We hope that understanding the stomach microbiota will make it possible to more easily prevent,detect and treat gastric cancer.展开更多
The aim of this work was evaluate the effects of terpinolene on acute inflammatory responses in mice.In vivo preclinical research using different inflammatory agents to induce acute responses and evaluate the effects ...The aim of this work was evaluate the effects of terpinolene on acute inflammatory responses in mice.In vivo preclinical research using different inflammatory agents to induce acute responses and evaluate the effects of terpinolene in orally treated mice.The acute inflammatory responses were induced by injecting phlogistic agents in the mice paw to observe the development of pain responses(formalin test)or edema(carrageenan,dextran,histamine,arachidonic acid,and prostaglandin).The antiedematogenic activity was also evaluated using a croton oil-induced ear edema model.Finally,cotton pellet-induced granuloma was used to carry out a pre-liminary evaluation of terpinolene in a chronic inflammatory model.Topically administered terpinolene(5,10,and 20 mg/mL)significantly inhibited ear edema development(by 33.82%,29.63%,and 33,30%,respectively).Following an oral administration,only the highest dose of the monoterpene(200 mg/kg)reduced the licking time of the formalin test in both phases 1(73.55%)and 2(96.61%).The carrageenan-induced edema signifi-cantly inhibited over time following the oral administration of terpinolene at 50 mg/kg(T1:47.74%,T2:54.67%,T3:48.63%,and T4:62.99%),100 mg/kg(T1:72.86%,T2:71.03%,T3:48.63%,and T4:57.83%),and 200 mg/kg(T1:43.22%,T2:34.11%,T3:36.47%,and T4:45.20%).On the other hand,only the dose of 200 (mg/kg)caused a significant reduction of the dextran-induced paw edema(T1:51.18%,T2:60%,T3:50.92%,and T4:65.15%).Regarding the participation of inflammatory pathways,the monoterpene(200 mg/kg,p.o.)had little impact on histamine-induced edema,while the edema induced by arachidonic acid was significantly reduced at all time-points(T1:37.04%,T2:24.32%,and T3:35.13%,and T4:35.53%),which was corroborated by the observation that the compound inhibited the response triggered by prostaglandin E2(PGE2),suggesting inter-ference with downstream signaling cascades.Finally,terpinolene(200 mg/kg,p.o.)reduced both the weight(21.43%)and total protein content(36.21%)of the cotton pellet-induced granuloma,indicating an anti-inflammatory activity in this chronic model.Terpinolene inhibited acute inflammatory responses and reduced granuloma development in vivo,possibly by interfering with the tissue changes orchestrated by inflammatory mediators such as histamine and PGE2.However,the molecular mechanisms underlying this pharmacological observation need to be confirmed by further research.展开更多
Objective To investigate whether exogenous hydrogen sulfide（H2S）protects high glucose（HG）-inducedH9c2 cardiomyocyte injury and inflammation response by inhibiting reactive oxygen species（ROS）-Toll-like receptor ...Objective To investigate whether exogenous hydrogen sulfide（H2S）protects high glucose（HG）-inducedH9c2 cardiomyocyte injury and inflammation response by inhibiting reactive oxygen species（ROS）-Toll-like receptor 4（TLR4）pathway.Methods Cell counter kit-8（CCK-8）assay was used to measure the cell viability,展开更多
Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biog...Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats,sertraline,and meloxicam,the inhibitors of arachidonic acid-cyclooxygenase-2/lipoxygenase(AA-COX-2/5-LO)pathways,were given to depressive rats.After the development of depression model by chronic unpredictable mild stress(CUMS)for 6 weeks,Successful modeling rats were selected and randomly divided into CUMS group and medication administration group.After given medicine,The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector(HPLC-ECD).Compared with the normal group,the concentration of norepinephrine(NE)significantly decreased and the concentrations of Tyrosine(Tyr),Tryptophan(Trp),3,4-dihydroxyphenyl acetic acid(DOPAC),3-methoxy-4-hydroxyphenylglycol(MHPG),homovanillic acid(HVA)and 5-hydroxyindoleacetic acid(5-HIAA)significantly increased in the CUMS group.Sertraline significantly inhibited the elevation of 5-HIAA.Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp,MHPG,and 5-HIAA level in a dose-dependent manner.Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner.The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMSinduced changes in biogenic amines.Compared with the single-dose lipoxygenase(5-LO)or Cyclooxygenase-2(COX-2)inhibitor,the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.展开更多
基金Supported by The Qianjiang Talent Project of Zhejiang Province,No.2013R10072the Natural Science Foundation of Zhejiang Province,Nos.LY14H160037 and LY12H16007
文摘AIM: To investigate the effect of oridonin on nuclear transcription factors and to study the relationship between biological behavior and inflammatory factors in human pancreatic cancer (BxPC-3) cells.
基金financial supported by the key research and development of general projects of Jiangxi province(20192BBF60026).
文摘Inflammatory bowel disease(IBD)is a chronic inflammatory lesion of the intestine,mainly manifested by infiltration of intestinal inflammatory cells and imbalance of gut microbiota.Conventional treatments for IBD include antibiotics,immunosuppressive agents,5-aminosalicylic acid,steroids and surgery,which have high toxic side effects.Resveratrol is a natural polyphenol,and its various derivatives have anti-oxidation and anti-inflammatory properties.In this paper,we comprehensively review the mechanism of resveratrol and its derivates to alleviate IBD by improving intestinal barrier,regulating the unbalanced gut microbiota,and targeting various inflammatory signaling pathways.
文摘The“longevity protein”SIRT5 could hold the key to delaying age-related muscle decline.A study led by researchers from the Institute of Zoology(IOZ)of the Chinese Academy of Sciences and Capital Medical University in Beijing reveals that SIRT5 mitigates skeletal muscle aging by blocking pro-inflammatory pathways.Published in Nature Metabolism on March 14,2025,the work identifies SIRT5’s interaction with protein kinase TBK1 as critical to preserving muscle mass and function.
基金supported by the Scientific and Technological Development Program of Jilin Province,China (Nos.20210203090SF and 20200403119SF)
文摘Inflammation represents a critical immune response triggered by cellular activities and inflammatory mediators following tissue damage.It plays a central role in the pathological progression of diverse diseases,including psychiatric disorders,cancer,and immunological conditions,rendering it an essential target for therapeutic intervention.Periodontitis,a prevalent oral inflammatory disease,is a leading cause of tooth loss and poses significant health challenges globally.Traditionally,inflammatory diseases such as periodontitis have been treated with systemic administration of synthetic chemicals.However,recent years have witnessed challenges,including drug resistance and microbial dysbiosis associated with these treatments.In contrast,natural products derived from Chinese medicine offer numerous benefits,such as high safety profiles,minimal side effects,innovative pharmacological mechanisms,ease of extraction,and multiple targets,rendering them viable alternatives to conventional antibiotics for treating inflammatory conditions.Numerous effective anti-inflammatory natural products have been identified in traditional Chinese medicine(TCM),including alkaloids,flavonoids,terpenoids,lignans,and other natural products that exhibit inhibitory effects on inflammation and are potential therapeutic agents.Several studies have confirmed the substantial anti-inflammatory and immunomodulatory properties of these compounds.This comprehensive review examines the literature on the anti-inflammatory effects of TCM-derived natural products from databases such as PubMed,Web of Science,and CNKI,focusing on terms like"inflammation","periodontitis","pharmacology",and"traditional Chinese medicine".The analysis systematically summarizes the molecular pharmacology,chemical composition,and biological activities of these compounds in inflammatory responses,alongside their mechanisms of action.This research seeks to deepen understanding of the mechanisms and biological activities of herbal extracts in managing inflammatory diseases,potentially leading to the development of promising new anti-inflammatory drug candidates.Future applications could extend to the treatment of various inflammatory conditions,including periodontitis.
基金supported by the National Natural Science Foundation of China(No.32171492)。
文摘Decabromodiphenyl ether(BDE-209)has been recognized for its adverse effects on the male reproductive system.The specific negative effects and underlying mechanisms through which BDE-209 impacts the reproductive function of offspring are not yet fully understood.The present study classified institute of cancer research(ICR)mice into control and BDE-209 treatment groups,administering doses of 0 and 75 mg/(kg·day),respectively.After 50 days of exposure,normal female mice were co-housed with the male mice,and their male offspring were sacrificed at 2 and 12 months of age.Paternal BDE-209 exposure reduced both sperm quantity and quality in offspring.Furthermore,exposure to BDE-209 resulted in DNA damage and the upregulation of the cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)DNA-sensing and inflammatory signaling pathways.The activation resulted in Z-DNA binding protein 1(ZBP1)binding to the mitochondrial antiviral signaling protein(MAVS),subsequently activating mitochondrial apoptosis in the testes.The activation of the cGAS-STING pathway inhibited mitophagy,leading to senescence in the testes of male offspring.In vitro studies indicated that the cGAS inhibitor RU320521(RU.521)effectively reversed the cGAS-STING pathway activation,alleviated the mitophagy inhibition,and decreased apoptosis and senescence in mouse spermatocyte line GC-2spd cells treated with BDE-209.The results showed that paternal BDE-209 exposure might disrupt spermatogenesis in mouse offspring by activating the cGAS-STING pathway and inhibiting mitophagy.This study provides essential data on the toxicity of BDE-209 to male reproduction and have important scientific and practical implications for maintaining biodiversity and population health in general.
基金The Department of Science&Technology of Fujian Province(Grant No.2017J01539 and 2020J01729)the Education Department Of Fujian Province(Grant No.JAT190239).
文摘Rheumatoid arthritis(RA)is one of the most common refractory diseases in the world,and traditional Chinese medicine Notopterygium(NE)has been used in the treatment of upper limb pain for a long time.NE can significantly reduce the expression of inflammatory pain target P2X3 receptor in rats with upper-limb arthritis.To verify the relationship between the mechanism of NE for“upper limb paralysis”and the P2X3 receptor-mediated PKC inflammatory response pathway,UPLC was taken to measure the exact medicinal substance of ethyl acetate from NE.Sprague Dawley rats were randomly divided into a blank group,a model group,a live-action group,and a positive group.The joint cavity was removed after 21 d.Moreover,a model group,a live group,and a positive group were also set up with RA-FLS cells in our in vitro study.The expressions of P2X3 and PKC inflammation pathway indicators were detected by Western blotting analysis.A P2X3 inhibitor(A-317491)acted on RA-FLS cells,and a model group and a positive group were set.Then the protein expression of PKC was detected.NE reduced the expressions of P2X3,Rab7,PKC,and NF-κB at the protein level in both systems.NE and P2X3 receptor antagonists reduced the expressions of key proteins in the PKC pathway in RA-FLS cells to similar extents,and their effects were not additive.NE could effectively improve the“forelimb pain”of RA rats,with a mechanism closely related to the P2X3/Rab7/PKC/NF-κB pathway.
基金supported by a grant(15-12A)from the Kentucky Spinal Cord and Head Injury Research Trust to JES and WXW。
文摘MicroRNAs(miRNAs)are small non-coding RNA molecules that regulate post-transcriptional gene expression and contribute to all aspects of cellular function.We previously reported that the activities of several mitochondria-enriched miRNAs regulating inflammation(i.e.,miR-142-3p,miR-142-5p,and miR-146a)are altered in the hippocampus at 3–12 hours following a severe traumatic brain injury.In the present study,we investigated the temporal expression profile of these inflammatory miRNAs in mitochondria and cytosol fractions at more chronic post-injury times following severe controlled cortical impact injury in rats.In addition,several inflammatory genes were analyzed in the cytosol fractions.The analysis showed that while elevated levels were observed in cytoplasm,the mitochondria-enriched miRNAs,miR-142-3p and miR-142-5p continued to be significantly reduced in mitochondria from injured hippocampi for at least 3 days and returned to near normal levels at 7 days post-injury.Although not statistically significant,miR-146a also remained at reduced levels for up to 3 days following controlled cortical impact injury,and recovered by 7 days.In contrast,miRNAs that are not enriched in mitochondria,including miR-124a,miR-150,miR-19b,miR-155,and miR-223 were either increased or demonstrated no change in their levels in mitochondrial fractions for 7 days.The one exception was that miR-223 levels were reduced in mitochondria at 1 day following injury.No major alterations were observed in sham operated animals.This temporal pattern was unique to mitochondria-enriched miRNAs and correlated with injury-induced changes in mitochondrial bioenergetics as well as expression levels of several inflammatory markers.These observations suggested a potential compartmental re-distribution of the mitochondria-enriched inflammatory miRNAs and may reflect an intracellular mechanism by which specific miRNAs regulate injury-induced inflammatory signaling.To test this,we utilized a novel peptide-based nanoparticle strategy for in vitro and in vivo delivery of a miR-146a mimic as a potential therapeutic strategy for targeting nuclear factor-kappa B inflammatory modulators in the injured brain.Nanoparticle delivery of miR-146a to BV-2 or SH-SY5Y cells significantly reduced expression of TNF receptor-associated factor 6(TRAF6)and interleukin-1 receptor-associated kinase 1(IRAK1),two important modulators of the nuclear factor-kappa B(NF-κB)pro-inflammatory pathway.Moreover,injections of miR-146a containing nanoparticles into the brain immediately following controlled cortical impact injury significantly reduced hippocampal TNF receptor-associated factor 6 and interleukin-1 receptor-associated kinase 1 levels.Taken together,our studies demonstrate the subcellular alteration of inflammatory miRNAs after traumatic brain injury and establish proof of principle that nanoparticle delivery of miR-146a has therapeutic potential for modulating pro-inflammatory effectors in the injured brain.All of the studies performed were approved by the University of Kentucky Institutional Animal Care and Usage Committee(IACUC protocol#2014-1300)on August 17,2017.
基金funded by the National Natural Science Foundation of China(32102646)the Natural Science Foundation of Guangdong Province,China(2020A1515110315)+1 种基金the Start-up Research Project of Maoming Laboratory,China(2021TDQD002)the China Agriculture Research System of MOF and MARA(cars-35)。
文摘Coronaviruses are widely transmissible between humans and animals, causing diseases of varying severity. Porcine enteric alphacoronavirus(PEAV) is a newly-discovered pathogenic porcine enteric coronavirus in recent years, which causes watery diarrhea in newborn piglets. The host inflammatory responses to PEAV and its metabolic regulation mechanisms remain unclear, and no antiviral studies have been reported. Therefore, we investigated the pathogenic mechanism and antiviral drugs of PEAV. The transcriptomic analysis of PEAV-infected host cells revealed that PEAV could upregulate lipid metabolism pathways. In lipid metabolism, steady-state energy processes, which can be mediated by lipid droplets(LDs), are the main functions of organelles. LDs are also important in viral infection and inflammation. In infected cells, PEAV increased LD accumulation, upregulated NF-κB signaling, promoted the production of the inflammatory cytokines IL-1β and IL-8, and induced cell death. Inhibiting LD accumulation with a DGAT-1 inhibitor significantly inhibited PEAV replication, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. The NF-κB signaling pathway inhibitor BAY11-7082 significantly inhibited LD accumulation and PEAV replication. Metformin hydrochloride also exerted anti-PEAV effects and significantly inhibited LD accumulation, downregulated the NF-κB signaling pathway, reduced the production of IL-1β and IL-8, and inhibited cell death. LD accumulation in the lipid metabolism pathway therefore plays an important role in the replication and pathogenesis of PEAV, and metformin hydrochloride inhibits LD accumulation and the inflammatory response to exert anti-PEAV activity and reducing pathological injury. These findings contribute new targets for developing treatments for PEAV infections.
基金supported by the National Natural Science Foundation of China(Nos.81673881 and 81202644)Hebei Province Natural Science Foundation Traditional Chinese Medicine Joint Fund Cultivation Project(No.H2022423375)Graduate Innovation Project of Hebei University of Chinese Medicine in 2023(No.XCXZZBS2023003).
文摘Background:Depression is becoming increasingly prevalent around the world,imposing a substantial burden on individuals,families,as well as society.Quercetin is known to be highly effective in treating depression.However,additional research is needed to dissect the mechanisms of its anti-depressive effects.Methods:For this study,Sprague-Dawley(SD)rats were randomized into the control,model,quercetin,or fluoxetine group.The latter three groups were exposed to chronic unpredictable mild stress(CUMS)for 42 d.The first two groups received saline solution daily via oral gavage.Meanwhile,the quercetin group was orally administered a quercetin suspension(52.08 mg/kg)every day,while the fluoxetine group was orally administered a fluoxetine solution(2.08 mg/kg).Here,fluoxetine served as the positive control drug to compare the therapeutic effects of quercetin.The experimental period was 6 weeks.Depressive behaviors in rats were assessed through various physiological and behavioral measures.Additionally,pathological changes in hippocampal tissues were examined using Nissl staining.Serum cytokines were detected using an enzymelinked immunosorbent assay(ELISA),and immunohistochemistry was employed to quantify the levels and integral optical density(IOD)values of ionized calcium binding adaptor molecule-1(Iba-1)expression in the brain.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to evaluate the mRNA levels of inflammatory indicators as well as toll-like receptor 4(TLR4),and nuclear factor-κappa B P65(NF-κB P65)in hippocampus.Western blot(WB)technique was employed to observe the protein levels of TLR4,NF-κB P65,and phospho-NF-κB P65(p-NF-κB P65).Results:After 42 d of exposure to CUMS,rats exhibited a slow increase in body weight,a reduction in food intake,an abnormal preference for sugar water,and aberrant open-field behaviors.Pathological analysis revealed the disintegration,rupture,interruption,and disorganization of hippocampal neuronal cells after CUMS exposure,along with a decrease in Nissl bodies in the CA1 region.This was accompanied by the elevated expression of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and interleukin-6(IL-6)in the serum and the upregulation of IL-1β,IL-6,and TNF-αmRNA expression in the hippocampus.Increases in Iba-1-positive cells and the IOD values of Iba-1 were detected in hippocampal microglia.Furthermore,TLR4 and NF-κB P65 mRNA and protein levels were upregulated in hippocampal tissues.Quercetin,an antidepressant,could alleviate depression-like symptoms in rats and downregulate inflammatory factors associated with the TLR4/NF-κB signaling pathway in hippocampal microglia,and its therapeutic effect was comparable to fluoxetine.Conclusion:In rat models of CUMS,quercetin may act as an antidepressant by inhibiting inflammation in hippocampal microglia via TLR4/NF-κB signaling pathway.These results offer experimental and theoretical support for applying quercetin in the clinical management of depression.
文摘COVID-19,as a concern in the world,can lead to death with a wide range of symptoms.Coronavirus,like other viral diseases,leads to the activation of inflammatory responses such as triggering the cytokine cascade.During the contact of the surface of the virus and its internal components with the human immune system,the path of expression and activation of cytokines begins.The body fights the virus through this operation and sometimes cell apoptosis.In the current review study,PubMed,Scopes,and Google Scholar were searched to provide information have shown the inflammasomes of COVID-19.In a review study,we examine the evidence that shows that COVID-19 activates inflammasomes;inflammasomes are cytosolic receptors that can identify microbial pathogens and endogenous signals resulting from stress or cell damage,including NLRP3(NLR Family Pyrin Domain Containing 3)type,NLRP4(NLR Family Pyrin Domain Containing 4),NLRP3.Through the activation of ASC and caspase 1,inflammasomes lead to the secretion of cytokines IL-1β(Interleukin-1 beta),IL-18(Interleukin-18),and IL6(Interleukin-6),TNF-α(Tumor Necrosis Factor-alpha).They can lead to the activation of inflammatory pathways.The results of this research can be useful in clarifying the relationship between the inflammatory pathways caused by the COVID-19 virus in people and the discovery of drugs in infected people.
基金supported by the National Natural Science Foundation of China,Nos.81070996(to ZW),81572151(to XYH)Shaanxi Provincial Key R&D Program,China,Nos.2020ZDLSF02-05(to ZW),2021ZDLSF02-10(to XYH)。
文摘As a classic noninvasive physiotherapy,photobiomodulation,also known as low-level laser therapy,is widely used for the treatment of many diseases and has anti-inflammatory and tissue repair effects.Photobiomodulation has been shown to promote spinal cord injury repair.In our previous study,we found that 810 nm low-level laser therapy reduced the M1 polarization of macrophages and promoted motor function recovery.However,the mechanism underlying this inhibitory effect is not clear.In recent years,transcriptome sequencing analysis has played a critical role in elucidating the progression of diseases.Therefore,in this study,we performed M1 polarization on induced mouse bone marrow macrophages and applied low-level laser therapy.Our sequencing results showed the differential gene expression profile of photobiomodulation regulating macrophage polarization.We analyzed these genes using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.Networks of protein-protein interactions and competing RNA endogenous networks were constructed.We found that photobiomodulation inhibited STAT3 expression through increasing the expression of miR-330-5p,and that miR-330-5p binding to STAT3 inhibited STAT3 expression.Inducible nitric oxide synthase showed trends in changes similar to the changes in STAT3 expression.Finally,we treated a mouse model of spinal cord injury using photobiomodulation and confirmed that photobiomodulation reduced inducible nitric oxide synthase and STAT3 expression and promoted motor function recovery in spinal cord injury mice.These findings suggest that STAT3 may be a potential target of photobiomodulation,and the miR-330-5p/STAT3 pathway is a possible mechanism by which photobiomodulation has its biological effects.
基金Supported by the National Natural Science Foundation of China(No.81102721,No.81573821 and No.81202809)Beijing Natural Science Foundation(No.7172185)+3 种基金Technologic Item of State Administration of Traditional Chinese Medicine(No.04-05LP30,JDZX2015262)Chinese National Scientific Fund for Post-doctor(No.2015M570220)Its Special Aid Item(No.2016T90194)the Key Technologies R&D Program of Shandong Province,China(No.2010 GSF 10289)
文摘Objective： To observe the effects of red yeast rice（RYR） on blood lipid levels, aortic atherosclerosis（AS）, and plaque stability in apolipoprotein E gene knockout（Apo E-/-） mice. Methods： Twentyfour Apo E-/-mice were fed with a high-fat diet starting from 6 weeks of age. Mice were randomized into three groups（n = 8 in each group）： model group（Apo E-/-group）, RYR group（Apo E-/-＋ RYR group）, and simvastatin group（Apo E-/-＋ simvastatin group）. Eight 6-week-old C57BL/6 mice were assigned as the control group and fed with a basic diet. After 36 weeks, plasma lipids and inflammatory factors were measured. Aortic atherosclerotic lesions by microscope, scanning electron microscope and transmission electron microscope were observed. Plasma levels of interleukin-6（IL-6） and tumor necrosis factor-α（TNF-α） were measured with enzymelinked immunosorbent assay. The level of high sensitivity C-reaction protein（Hs-CRP） was detected by the scattering immunoturbidimetric assay. Protein expression of matrix metalloproteinase-9（MMP-9） and nuclear factor κB（NF-κB） in aorta were tested by immunohistochemistry. Results： Compared with the model group, treatment with RYR significantly decreased the levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol, lipoprotein（a）, and apolipoprotein B100 in Apo E-/-mice（P〈0.01）. Compared with the model group, treatment with RYR decreased the levels of Hs-CRP, IL-6, and TNF-α（P〈0.01）. RYR also reduced the protein levels of NF-κB and MMP-9 of the aorta. Conclusions： RYR has the anti-atherosclerotic and stabilizing unstable plaque effects. The mechanism might be related to the inflammatory signaling pathways.
基金the Yangzhou Science and Technology Bureau Social Development Project of Jiangsu Province[No.YZ2018087]the training project of Key Talents of Youth Medicine in Jiangsu Province,China[QNRC2016330]+1 种基金the Key Disease Standardization Diagnosis and Treatment Project in Jiangsu Province[BE2015664]the Academic Science and Technology Innovation Fund for College Students[x20180714].
文摘Gastric cancer is closely related to the stomach microbiota,especially Helicobacter pylori.Numerous reports and clinical studies have shown that microbial behavior in the stomach may lead to pathological changes in the gastrointestinal tract of the host,which ultimately leads to the production and development of gastric cancer.This review outlines the major pathogenic processes of Helicobacter pylori in the stomach,specifically focusing on Cag A,Vac A,inflammatory pathways and oxidative stress.In addition,we describe the effects of some non-Helicobacter pylori factors,such as other microbiota,alcohol,and tobacco,on the carcinogenesis induced by Helicobacter pylori.The effects of family history are also taken into account.We hope that understanding the stomach microbiota will make it possible to more easily prevent,detect and treat gastric cancer.
基金financial support provided of support of the Brazilian agencies CAPES,FUNCAP,CNPq,and FINEPNacional Institute of Science and Technology-Ethnobiology,Bioprospecting and Nature Conservation/CNPq/FACEPE.
文摘The aim of this work was evaluate the effects of terpinolene on acute inflammatory responses in mice.In vivo preclinical research using different inflammatory agents to induce acute responses and evaluate the effects of terpinolene in orally treated mice.The acute inflammatory responses were induced by injecting phlogistic agents in the mice paw to observe the development of pain responses(formalin test)or edema(carrageenan,dextran,histamine,arachidonic acid,and prostaglandin).The antiedematogenic activity was also evaluated using a croton oil-induced ear edema model.Finally,cotton pellet-induced granuloma was used to carry out a pre-liminary evaluation of terpinolene in a chronic inflammatory model.Topically administered terpinolene(5,10,and 20 mg/mL)significantly inhibited ear edema development(by 33.82%,29.63%,and 33,30%,respectively).Following an oral administration,only the highest dose of the monoterpene(200 mg/kg)reduced the licking time of the formalin test in both phases 1(73.55%)and 2(96.61%).The carrageenan-induced edema signifi-cantly inhibited over time following the oral administration of terpinolene at 50 mg/kg(T1:47.74%,T2:54.67%,T3:48.63%,and T4:62.99%),100 mg/kg(T1:72.86%,T2:71.03%,T3:48.63%,and T4:57.83%),and 200 mg/kg(T1:43.22%,T2:34.11%,T3:36.47%,and T4:45.20%).On the other hand,only the dose of 200 (mg/kg)caused a significant reduction of the dextran-induced paw edema(T1:51.18%,T2:60%,T3:50.92%,and T4:65.15%).Regarding the participation of inflammatory pathways,the monoterpene(200 mg/kg,p.o.)had little impact on histamine-induced edema,while the edema induced by arachidonic acid was significantly reduced at all time-points(T1:37.04%,T2:24.32%,and T3:35.13%,and T4:35.53%),which was corroborated by the observation that the compound inhibited the response triggered by prostaglandin E2(PGE2),suggesting inter-ference with downstream signaling cascades.Finally,terpinolene(200 mg/kg,p.o.)reduced both the weight(21.43%)and total protein content(36.21%)of the cotton pellet-induced granuloma,indicating an anti-inflammatory activity in this chronic model.Terpinolene inhibited acute inflammatory responses and reduced granuloma development in vivo,possibly by interfering with the tissue changes orchestrated by inflammatory mediators such as histamine and PGE2.However,the molecular mechanisms underlying this pharmacological observation need to be confirmed by further research.
文摘Objective To investigate whether exogenous hydrogen sulfide（H2S）protects high glucose（HG）-inducedH9c2 cardiomyocyte injury and inflammation response by inhibiting reactive oxygen species（ROS）-Toll-like receptor 4（TLR4）pathway.Methods Cell counter kit-8（CCK-8）assay was used to measure the cell viability,
基金supported by pharmacy school of Chongqing Medical University.This research work was financially supported by Research Fund of Chongqing Science&Technology Commission(No:cstc2013jcyjA10040)Research Start-up Fund of Pharmacy School of Chongqing Medical University.
文摘Inflammation drives the development of depression and may affect neurotransmitters and thus neurocircuits increase the risk of depression.To investigate the influence of inhibition of inflammatory pathways on the biogenic amine neurotransmitters metabolism in depressive rats,sertraline,and meloxicam,the inhibitors of arachidonic acid-cyclooxygenase-2/lipoxygenase(AA-COX-2/5-LO)pathways,were given to depressive rats.After the development of depression model by chronic unpredictable mild stress(CUMS)for 6 weeks,Successful modeling rats were selected and randomly divided into CUMS group and medication administration group.After given medicine,The biogenic amine neurotransmitters in rat cortex and hippocampus were measured by high-performance liquid chromatography equipped with an electrochemical detector(HPLC-ECD).Compared with the normal group,the concentration of norepinephrine(NE)significantly decreased and the concentrations of Tyrosine(Tyr),Tryptophan(Trp),3,4-dihydroxyphenyl acetic acid(DOPAC),3-methoxy-4-hydroxyphenylglycol(MHPG),homovanillic acid(HVA)and 5-hydroxyindoleacetic acid(5-HIAA)significantly increased in the CUMS group.Sertraline significantly inhibited the elevation of 5-HIAA.Meloxicam inhibited the decrease of NE level in CUMS-induced rat and the increase of Trp,MHPG,and 5-HIAA level in a dose-dependent manner.Caffeic acid inhibited the decrease of NE and the increase of Trp and MHPG in a dose-dependent manner.The inhibition of AA-COX-2/5-LO pathways can improve the behaviors of depression rats and suppress CUMSinduced changes in biogenic amines.Compared with the single-dose lipoxygenase(5-LO)or Cyclooxygenase-2(COX-2)inhibitor,the combination treatment with meloxicam 1 mg/kg and caffeic acid 10 mg/kg have no significant improvement in CUMS-induced depression behavior and the level of cortical monoamine neurotransmitters and their metabolites.
