Aim To study the effect and mechanism of Chlorogenic acid in allergic rhinitis （AR） mice. MethodsAR was induced in BALB/c mice according to a published method with ovalbumin （OVA）. The AR model was de- veloped by ...Aim To study the effect and mechanism of Chlorogenic acid in allergic rhinitis （AR） mice. MethodsAR was induced in BALB/c mice according to a published method with ovalbumin （OVA）. The AR model was de- veloped by intraperitoneal injection of adjuvant suspension on every other day for 7 times. Adjuvant suspension in- clude 50 μg of OVA and 2rag of AI（OH） s, which were combined in 2ml of normal saline （NS）. Then, the mice received a nasal drip of 10% OVA daily for 10days, and in normal control were dripped NS. After administration with 50 mg· kg^-1, 100 mg · kg^-1 and 200 mg · kg^-1 of Chlorogenic acid for 30min, The mice were attacked lo- cally for 10 days. We observed behavior analysis, evaluated the weight of nosal draingage, related the index of thy- mus and spleen, determined the effect of Chlorogenic acid on the contents of cytokines, IgE and histamine by ELISA in AR mice and analyzed the mRNA expression of inflammatory cytokines （IL-4, IL-5, IL-10, IFN-y） in the nasal mucosa tissues samples by RT-PCR. Results Chlorogenic acid decreased the number of nose-scratching events in 10min, the weight of nosal draingage, the index of spleen, the content of IL-4 in nasal lavage fluid（NLF） and the contents of cytokines, IgE and histamine in serum; while increased the index of thymus, the content of IFN-γ in NLF, the contents of IFN-γ in serum and the rate of IFN-γ/IL-4 ; The data showed a statistically signifi- cant up-regulation of IFN-γ mRNA expressions and down-regulation of IL-4mRNA, IL-5mRNA, IL-10mRNA ex- pressions after adiminstration of Chlorogenic acid. Conclusion Chlorogenic acid might exert the effect in AR mice through regulating the balance of Thl and Th2.展开更多
Aim The present study aimed to investigate anti-inflammatory activity of 6-AP on murine model of aller- gic contact dermatitis （ACD）. Methods 6＇-acetylpaeoniflorin （6-AP） was synthesized from paeoniflorin （Pae）...Aim The present study aimed to investigate anti-inflammatory activity of 6-AP on murine model of aller- gic contact dermatitis （ACD）. Methods 6＇-acetylpaeoniflorin （6-AP） was synthesized from paeoniflorin （Pae） via acetylation and the structure was characterized by 1H-NMR, 13C-NMR and EI-MS. ACD model was established by repeated application of dinitrochlorobenzene （DNCB） to induce skin immune inflammation. The mice were oral- ly administered 6-AP （35, 70, 140 mg. kg-1 ·d^-l）, Pae （70 rag. kg-1·d^-1） and prednisone （Pre, 5 rag. kg^- 1· d^-1 ） from day 1 to day 7 after Cutaneous inflammation was evaluated by ear swelling and histological exami- nation. Splenocyte proliferation was assayed by the 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyl-2H tetrazolium bromide assay. The cytokine production in the splenocytes was measured by enzyme-linked immunosorbent assay. Results Topical application of DNCB to the skin provoked obvious swelling and inflammatory cell infiltration. 6- AP significantly inhibited ear swelling, decreased inflammatory cell infiltration and epidermal keratinization. Ad- dtionally, 6-AP obviously alleviated the hyperplasia of red pulp and germinal center （GC） appearance, decreased spleen index, decreased spleen index, and inhibited splenocyte proliferation in ACD model, compared to that of Pae. Further, the study indicated that 6-AP treatment could increase IL-10 level, while reduce IL-17 level in splenocytes simultaneously. The correlation analysis displayed significantly positive correlations between IL-17 level and the severity of skin inflammation, while negative correlations between IL-10 level and skin inflammation. Con- clusion 6-AP has a significantly higher anti-inflammatory effect than Pae, and it may be a useful treatment for ACD.展开更多
OBJECTIVE To evaluate the in vivo anti-inflammatory and allergic rhinitis(AR)alleviating effect as well as in vitro antimicrobial activities of Artemisia ordosica Krasch.(AOK)extracts to verify its ethno-medicinal cla...OBJECTIVE To evaluate the in vivo anti-inflammatory and allergic rhinitis(AR)alleviating effect as well as in vitro antimicrobial activities of Artemisia ordosica Krasch.(AOK)extracts to verify its ethno-medicinal claims.METHODS Crude extracts(methanol/95%-ethanol/ethyl acetate)of AOK root/stem/leaf and fractions(petroleum ether/ethyl acetate/n-butanol/aqueous)of AOK root extractwere prepared.Xylene-induced ear swelling model in mouse and ovalbumin(OVA)-induced AR model in guinea pig were established.Ear swelling degrees of mice were measured.The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR.The serum levels of histamine,INF-γ,IL-2/4/10,and VCAM-1 were measured by ELISA assay.The histological changes of nasal mucosa were investigated by light microscope after H&E staining.Antimicrobial activities of AOK extracts were also tested.LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism.RESULTS In ear-swelling model,extract(100.00 mg·kg^-1)from the ethyl acetate layer of 95%ethanol(100.00 mg·kg^-1)showed better swelling inhibition in mice than positive control(dexamethasone,191.91 mg·kg^-1).In AR model,extract from the ethyl acetate layer of 95%ethanol significantly alleviated the AR symp⁃toms in guinea pigs,decreased the serum levels of histamine,INF-γ,IL-2/4/10,and VCAM-1,and reduced the infiltration of eosinophil in nasal mucosa.For Staphylococcus aureus,the ethyl acetate extract of AOK stem showed the highest inhibi⁃tion(MIC=1.25 g·L^-1),for Escherichia coli,n-butanol layer of 95%ethanol extract of AOK root showed the highest inhibi⁃tion(MIC=15.00 g·L^-1),for Candida glabrata,95%-ethanol extract of AOK stem showed the best inhibition(MIC=0.064 g·L^-1),while ethyl acetate and n-butanol layers showed similar inhibition on MRSA(MIC=7.50 g·L-1).LC-MS/MS characteriza⁃tion showed that dicaffeoylquinic acids account for more than 30%of ethyl acetate layer of AOK extract.Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes.CONCLUSION Extracts from AOK had interesting anti-inflammatory activity in mice,alleviating effect against OVA-induced AR in guinea pigs,and antimicrobial activities in vitro,which support the ethno-medicinal use of it.The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well.These findings highlighted the impor⁃tance of natural product chemistry study of AOK.展开更多
Epidemiological studies have shown that there is a link between asthma and brain damage,but toxicological studies have not fully confirmed yet,especially the effects of asthma on the brain. In this study,at first,we e...Epidemiological studies have shown that there is a link between asthma and brain damage,but toxicological studies have not fully confirmed yet,especially the effects of asthma on the brain. In this study,at first,we explore the effects of asthma on the brain through the establishment of an allergic asthma model. Then PM_(2.5),a typical outdoor air pollutant and formaldehyde,a typical indoor air pollutant were selected to be closer to the true environment and find whether there is any synergism between them. In this study,an ovalbumin( OVA)-sensitized mice asthma model was established. 30 male Balb/c mice were randomly divided into 5 groups:( 1) saline control group,( 2) OVA-sensitized group,( 3) OVA-combined with formaldehyde exposure group,( 4) OVA-combined with PM_(2.5) exposure group,( 5) Combination of OVA,formaldehyde and PM_(2.5) exposure group. The mice were inhaled with formaldehyde or/and instilled with PM_(2.5) from day 1 to 18. The mice asthma model was developed by OVA sensitization and challenge. The mice were sensitized with OVA+Al( OH)3( 5 mg OVA and 175 mg Al( OH)3 in 30 m L saline each time) or saline( 30 m L saline each time) by intraperitoneal injection on day 1,7 and 14.This was then followed by an aerosol challenge in 1% OVA( 30 min·d^(-1)) from day 19 to 25( 7 times) using an ultrasonic nebulizer. On the 26 th day,the organ coefficient of mice brain was counted,then the contents of oxidative stress of mice brain were measured,including reactive oxygen species( ROS),glutathione( GSH) and malondialdehyde( MDA),and the concentrations of NF-κB and interleukin-1β( IL-1β) were detected by using ELISA kits.Detection of interleukin-6( IL-6) was made with immunohistochemical method. Histological assay for brain was also conducted. In our results,all the OVA treated groups showed a significant increase of ROS and a significant decrease of GSH contents when compared with the control group. Except OVA-sensitized group,other OVA treated groups also showed a significant increase of MDA contents when compared with the control group,and MDA contents of OVA-sensitized group showed significant change when compared to the combined exposure group. In ROS and GSH,combined exposure showed some joint effect compared with single exposure. When OVA was applied in combination with formaldehyde and PM_(2.5),NF-κB was activated. And all the OVA treated groups showed increased levels of IL-1β and IL-6 compared with the control group. And the combined exposure showed an aggravated effect when compared with OVA-sensitized group. Histopathological observation of the hippocampus in mice brain clearly showed the difference of eosin( EO) stained neurons in the combined exposure group compared with the control group and OVA-sensitized group. The pyramidal neurons of the mice with allergic asthma exposed to formaldehyde and/or PM_(2.5) had been reduced in number,the cells were swollen and the dendrites had disappeared. Allergic asthma can cause damage to the brain through oxidative stress. Exposure to formaldehyde and PM_(2.5) will increase the damage caused by allergic asthma to the brain,which may be mediated by oxidative stress and NF-κB activation.This promotes the release of the inflammatory factors,resulting in increased inflammation.展开更多
文摘Aim To study the effect and mechanism of Chlorogenic acid in allergic rhinitis （AR） mice. MethodsAR was induced in BALB/c mice according to a published method with ovalbumin （OVA）. The AR model was de- veloped by intraperitoneal injection of adjuvant suspension on every other day for 7 times. Adjuvant suspension in- clude 50 μg of OVA and 2rag of AI（OH） s, which were combined in 2ml of normal saline （NS）. Then, the mice received a nasal drip of 10% OVA daily for 10days, and in normal control were dripped NS. After administration with 50 mg· kg^-1, 100 mg · kg^-1 and 200 mg · kg^-1 of Chlorogenic acid for 30min, The mice were attacked lo- cally for 10 days. We observed behavior analysis, evaluated the weight of nosal draingage, related the index of thy- mus and spleen, determined the effect of Chlorogenic acid on the contents of cytokines, IgE and histamine by ELISA in AR mice and analyzed the mRNA expression of inflammatory cytokines （IL-4, IL-5, IL-10, IFN-y） in the nasal mucosa tissues samples by RT-PCR. Results Chlorogenic acid decreased the number of nose-scratching events in 10min, the weight of nosal draingage, the index of spleen, the content of IL-4 in nasal lavage fluid（NLF） and the contents of cytokines, IgE and histamine in serum; while increased the index of thymus, the content of IFN-γ in NLF, the contents of IFN-γ in serum and the rate of IFN-γ/IL-4 ; The data showed a statistically signifi- cant up-regulation of IFN-γ mRNA expressions and down-regulation of IL-4mRNA, IL-5mRNA, IL-10mRNA ex- pressions after adiminstration of Chlorogenic acid. Conclusion Chlorogenic acid might exert the effect in AR mice through regulating the balance of Thl and Th2.
文摘Aim The present study aimed to investigate anti-inflammatory activity of 6-AP on murine model of aller- gic contact dermatitis （ACD）. Methods 6＇-acetylpaeoniflorin （6-AP） was synthesized from paeoniflorin （Pae） via acetylation and the structure was characterized by 1H-NMR, 13C-NMR and EI-MS. ACD model was established by repeated application of dinitrochlorobenzene （DNCB） to induce skin immune inflammation. The mice were oral- ly administered 6-AP （35, 70, 140 mg. kg-1 ·d^-l）, Pae （70 rag. kg-1·d^-1） and prednisone （Pre, 5 rag. kg^- 1· d^-1 ） from day 1 to day 7 after Cutaneous inflammation was evaluated by ear swelling and histological exami- nation. Splenocyte proliferation was assayed by the 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyl-2H tetrazolium bromide assay. The cytokine production in the splenocytes was measured by enzyme-linked immunosorbent assay. Results Topical application of DNCB to the skin provoked obvious swelling and inflammatory cell infiltration. 6- AP significantly inhibited ear swelling, decreased inflammatory cell infiltration and epidermal keratinization. Ad- dtionally, 6-AP obviously alleviated the hyperplasia of red pulp and germinal center （GC） appearance, decreased spleen index, decreased spleen index, and inhibited splenocyte proliferation in ACD model, compared to that of Pae. Further, the study indicated that 6-AP treatment could increase IL-10 level, while reduce IL-17 level in splenocytes simultaneously. The correlation analysis displayed significantly positive correlations between IL-17 level and the severity of skin inflammation, while negative correlations between IL-10 level and skin inflammation. Con- clusion 6-AP has a significantly higher anti-inflammatory effect than Pae, and it may be a useful treatment for ACD.
基金Science Foundation of Inner Mongolia(2017MS0870)Science and Technology Planning Project of Inner Mongolia(201702139)
文摘OBJECTIVE To evaluate the in vivo anti-inflammatory and allergic rhinitis(AR)alleviating effect as well as in vitro antimicrobial activities of Artemisia ordosica Krasch.(AOK)extracts to verify its ethno-medicinal claims.METHODS Crude extracts(methanol/95%-ethanol/ethyl acetate)of AOK root/stem/leaf and fractions(petroleum ether/ethyl acetate/n-butanol/aqueous)of AOK root extractwere prepared.Xylene-induced ear swelling model in mouse and ovalbumin(OVA)-induced AR model in guinea pig were established.Ear swelling degrees of mice were measured.The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR.The serum levels of histamine,INF-γ,IL-2/4/10,and VCAM-1 were measured by ELISA assay.The histological changes of nasal mucosa were investigated by light microscope after H&E staining.Antimicrobial activities of AOK extracts were also tested.LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism.RESULTS In ear-swelling model,extract(100.00 mg·kg^-1)from the ethyl acetate layer of 95%ethanol(100.00 mg·kg^-1)showed better swelling inhibition in mice than positive control(dexamethasone,191.91 mg·kg^-1).In AR model,extract from the ethyl acetate layer of 95%ethanol significantly alleviated the AR symp⁃toms in guinea pigs,decreased the serum levels of histamine,INF-γ,IL-2/4/10,and VCAM-1,and reduced the infiltration of eosinophil in nasal mucosa.For Staphylococcus aureus,the ethyl acetate extract of AOK stem showed the highest inhibi⁃tion(MIC=1.25 g·L^-1),for Escherichia coli,n-butanol layer of 95%ethanol extract of AOK root showed the highest inhibi⁃tion(MIC=15.00 g·L^-1),for Candida glabrata,95%-ethanol extract of AOK stem showed the best inhibition(MIC=0.064 g·L^-1),while ethyl acetate and n-butanol layers showed similar inhibition on MRSA(MIC=7.50 g·L-1).LC-MS/MS characteriza⁃tion showed that dicaffeoylquinic acids account for more than 30%of ethyl acetate layer of AOK extract.Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes.CONCLUSION Extracts from AOK had interesting anti-inflammatory activity in mice,alleviating effect against OVA-induced AR in guinea pigs,and antimicrobial activities in vitro,which support the ethno-medicinal use of it.The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well.These findings highlighted the impor⁃tance of natural product chemistry study of AOK.
基金National Natural Science Foundation of China (No: 21577045).
文摘Epidemiological studies have shown that there is a link between asthma and brain damage,but toxicological studies have not fully confirmed yet,especially the effects of asthma on the brain. In this study,at first,we explore the effects of asthma on the brain through the establishment of an allergic asthma model. Then PM_(2.5),a typical outdoor air pollutant and formaldehyde,a typical indoor air pollutant were selected to be closer to the true environment and find whether there is any synergism between them. In this study,an ovalbumin( OVA)-sensitized mice asthma model was established. 30 male Balb/c mice were randomly divided into 5 groups:( 1) saline control group,( 2) OVA-sensitized group,( 3) OVA-combined with formaldehyde exposure group,( 4) OVA-combined with PM_(2.5) exposure group,( 5) Combination of OVA,formaldehyde and PM_(2.5) exposure group. The mice were inhaled with formaldehyde or/and instilled with PM_(2.5) from day 1 to 18. The mice asthma model was developed by OVA sensitization and challenge. The mice were sensitized with OVA+Al( OH)3( 5 mg OVA and 175 mg Al( OH)3 in 30 m L saline each time) or saline( 30 m L saline each time) by intraperitoneal injection on day 1,7 and 14.This was then followed by an aerosol challenge in 1% OVA( 30 min·d^(-1)) from day 19 to 25( 7 times) using an ultrasonic nebulizer. On the 26 th day,the organ coefficient of mice brain was counted,then the contents of oxidative stress of mice brain were measured,including reactive oxygen species( ROS),glutathione( GSH) and malondialdehyde( MDA),and the concentrations of NF-κB and interleukin-1β( IL-1β) were detected by using ELISA kits.Detection of interleukin-6( IL-6) was made with immunohistochemical method. Histological assay for brain was also conducted. In our results,all the OVA treated groups showed a significant increase of ROS and a significant decrease of GSH contents when compared with the control group. Except OVA-sensitized group,other OVA treated groups also showed a significant increase of MDA contents when compared with the control group,and MDA contents of OVA-sensitized group showed significant change when compared to the combined exposure group. In ROS and GSH,combined exposure showed some joint effect compared with single exposure. When OVA was applied in combination with formaldehyde and PM_(2.5),NF-κB was activated. And all the OVA treated groups showed increased levels of IL-1β and IL-6 compared with the control group. And the combined exposure showed an aggravated effect when compared with OVA-sensitized group. Histopathological observation of the hippocampus in mice brain clearly showed the difference of eosin( EO) stained neurons in the combined exposure group compared with the control group and OVA-sensitized group. The pyramidal neurons of the mice with allergic asthma exposed to formaldehyde and/or PM_(2.5) had been reduced in number,the cells were swollen and the dendrites had disappeared. Allergic asthma can cause damage to the brain through oxidative stress. Exposure to formaldehyde and PM_(2.5) will increase the damage caused by allergic asthma to the brain,which may be mediated by oxidative stress and NF-κB activation.This promotes the release of the inflammatory factors,resulting in increased inflammation.
