Objective:To evaluate the effect of myricetin on ovalbumin(OVA)-induced allergic rhinitis in mice.Methods:Mice were sensitized and challenged using OVA(5%,500 mL)intraperitoneally and intranasally,respectively,on an a...Objective:To evaluate the effect of myricetin on ovalbumin(OVA)-induced allergic rhinitis in mice.Methods:Mice were sensitized and challenged using OVA(5%,500 mL)intraperitoneally and intranasally,respectively,on an alternative day for 14 days,followed by administration of myricetin(50,100,and 200 mg/kg)till day 21.Nasal symptoms,biochemical parameters,protein expressions,and histopathology were observed.Results:OVA-induced increased nasal symptoms including rubbing,sneezing,and discharge were significantly reduced by myricetin(100and 200 mg/kg)(P<0.05).Myricetin also protected against histamine challenge and attenuated elevated serum immunoglobulin E(IgE;total and OVA-specific),total IgG1,andβ-hexosaminidase levels,as well as leukotriene C4 and interleukins levels in nasal lavage fluid(P<0.05).Western blot analysis showed that myricetin significantly upregulated the protein expression of T-box expressed in T cells,while downregulating the protein expression of GATA binding protein 3,NF-κB,and IκB-α(P<0.05).Additionally,OVA-induced histopathological abberations in the nasal mucosa was markedly ameliorated by myricetin treatment(P<0.05).Conclusions:Myricetin exerts anti-allergic effects against OVAinduced allergic rhinitis via regulating Th1/Th2 balance.展开更多
Objective:To evaluate the therapeutic effect of Glycyrrhetinic Acid on cough variant asthma(CVA)mice and to investigate the possible mechanism in reducing lung inflammation.Methods:48 young female Balb/c mice were div...Objective:To evaluate the therapeutic effect of Glycyrrhetinic Acid on cough variant asthma(CVA)mice and to investigate the possible mechanism in reducing lung inflammation.Methods:48 young female Balb/c mice were divided into Control,CVA,Prednisone Acetate,Glycyrrhetinic Acid high-dose,Glycyrrhetinic Acid middle-dose and Glycyrrhetinic Acid lowdose groups randomly,with 8 mice in each group.The CVA mice model was established by ovalbumin(OVA)sensitization and OVA challenge,the animal asthma behavior was observed after drug administration,and the index of the lung of mice were recorded.The level of OVAsIgE in the bronchoalveolar lavage fluid(BALF)was tested by ELISA.The pathological changes of the lung tissue were observed by Hematoxylin and Eosin(H&E)staining.The protein expressions of T-bet,IFN-γ,Gata3,IL-4 and IL-13 in the lung tissue were determined by Western blot.Results:Compared with the CVA group,the index of lung of mice,the OVA-sIgE level in BALF and expression levels of Th2-related factor in the lung tissue of mice in Prednisone Acetate and Glycyrrhetinic Acid groups were significantly decreased(P<0.05 or P<0.01),the infiltration of inflammatory cells in the lung tissue was reduced,while expressions of Th1-related factor in the lung tissue was significantly increased(P<0.05 or P<0.01).Conclusion:Glycyrrhetinic acid has therapeutic effect on CVA mice,the underlying mechanism of Glycyrrhetinic acid alleviating lung impairment and airway inflammation may be associated with mediating the Th1/Th2 imbalance in the lung tissue.展开更多
Objective:To study the influence of budesonide and salbutamol atomization inhalation on Th17/Treg balance in patients with bronchial asthma and its correlation with airway remodeling.Methods:A total of 90 patients wit...Objective:To study the influence of budesonide and salbutamol atomization inhalation on Th17/Treg balance in patients with bronchial asthma and its correlation with airway remodeling.Methods:A total of 90 patients with bronchial asthma who received systemic treatment in our hospital between July 2013 and April 2016 were divided into control group (n=45) and observation group (n=45) according to random number table. Patients in the control group were treated with salbutamol atomization inhalation alone while those in observation group were treated with budesonide and salbutamol atomization inhalation. The Th17/Treg ratio in peripheral blood as well as serum contents of airway remodeling-related indicators was compared between two groups before and after treatment. The correlation between Th17/Treg balance and airway remodeling in patients with bronchial asthma was detected by Pearson test. Results:Before treatment, the differences in peripheral blood Th17/Treg ratio as well as serum contents of inflammatory mediators, growth factor indexes and collagen metabolism indexes were not statistically significant between two groups of patients. After treatment, peripheral blood Th17/Treg ratio in observation group was lower than that in control group, serum CRP, IL-8, IL-13 and TNF- contents in observation group were lower than those in control group, serum PDGF-BB, b-FGF and VEGF contents in observation group were lower than those in control group, and serum HA, PCⅢ and LN contents in observation group were lower than those in control group. The Th17/Treg ratio in patients with bronchial asthma after treatment was positively correlated with the levels of airway remodeling-related indexes.Conclusion:Budesonide combined with salbutamol atomization inhalation can optimize the Th17/Treg balance in patients with bronchial asthma, and Th17/Treg is directly correlated to the degree of airway remodeling.展开更多
Objective:Explore the role of Th1/Th2 balance in the pathogenesis of primary dysmenorrhea through study the effect of Th1/Th2 balance drift on serum prostaglandin F_(2α),prostaglandin,6-keto-prostaglandin F_(1α),TXB...Objective:Explore the role of Th1/Th2 balance in the pathogenesis of primary dysmenorrhea through study the effect of Th1/Th2 balance drift on serum prostaglandin F_(2α),prostaglandin,6-keto-prostaglandin F_(1α),TXB2,COX-2,AVP and OT in Primary Dysmenorrhea Rats with cold coagulation and blood stasis syndrome.Method:The rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome was established.On the basis of this model,Th1 shift model and Th2 shift model were established.The rats were divided into blank group,model group,Th1 shifting group and Th2 shifting group.The writhing reaction of rats in each group was compared,and the contents of PGF_(2α),PGE_(2),6-keto-PGF_(1α),TXB2,COX-2,AVP and OT in serum were detected.Results:Writhing latency:There was no significant difference between Th1 and Th2 shifting groups(P>0.05),Th2 shifting group was shorter than Th1 shifting group(P<0.05).Writhing times in 30 minutes:Compared with the model group,the writhing times of Th1 shifting group decreased significantly(P<0.01),while Th2 shifting group increased significantly(P<0.01).Compared with the blank group,the contents of PGF_(2α),TXB2,COX-2,AVP and OT were increased(P<0.05,P<0.01),and the contents of 6-keto-PGF_(1α)and PGE_(2)were decreased(P<0.01).Compared with the model group,the contents of PGF_(2α),TXB2,COX-2 and AVP in Th1 shifting group were decreased(P<0.05,P<0.01),and the contents of 6-keto-PGF_(1α)and PGE_(2)were increased(P<0.01),while the contents of PGF_(2α),TXB2,COX-2,AVP and OT in Th2 shifting group were increased(P<0.01),and the contents of 6-keto-PGF_(1α)and PGE_(2)were decreased(P<0.01).Conclusion:The intervention of Th1/Th2 cell balance on the expression of PGF_(2α),PGE_(2),6-keto-PGF_(1α),TXB2,COX-2,AVP and OT may be one of the pathogenesis of PD with cold coagulation and blood stasis syndrome.展开更多
The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balanc...The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balance under a strong Thl-polarizing condition. Therefore, the purpose of our study was to examine the effect of vitamin A metabolite allotrans retinoic acid （ATRA） on ThloTh2 differentiation in CD4~ T cells under GATA-3 deficiency, which can induce Thl-polarizing condition. In the present study, GATA-3 deficiency T cells were induced by siRNA and checked by real-time quantitative PCR and western blot. GATA-3 deficiency CD4＋ T cells and normal CD4＋ T were treated for 48 h with or without ATRA.展开更多
OBJECTIVE Atherosclerosis(AS)is a chronic inflammatory disease characterized by the accumulation of lipids,vascular fibrosis,and inflammation.Paeonol(Pae)is a natural phenolic compounds isolated from a traditional Chi...OBJECTIVE Atherosclerosis(AS)is a chronic inflammatory disease characterized by the accumulation of lipids,vascular fibrosis,and inflammation.Paeonol(Pae)is a natural phenolic compounds isolated from a traditional Chinese medicine,Cortex Moutan,which exhibits anti-AS effects.Our previous work demonstrated that gut microbiota plays an important role during AS treatment as it affects the efficacy of Pae.However,the mechanism of Pae in protecting against vascular fibrosis as related to gut microbiota has yet to be elucidated.To investigate the anti-fibrosis effect of Pae on AS mice and demonstrate the underlying gut microbiota-dependent mechanism.METHODS ApoE-/-mice were fed with high-fat-diet(HFD)to replicate the AS model.HE and Masson staining were used to observe the plaque formation and collagen deposition.Gut microbiota alteration and short-chain fatty acids(SCFAs)production were analyzed through 16S rRNA sequencing and LC-MS/MS.The frequency of immune cells in spleen were phenotyped by flow cytometry.The mRNA expression of aortic inflammatory cytokines were detected by qRT-PCR.The protein expression of LOX and fibrosis related indicators were examined by Western blotting.RESULTS Pae restricted the development of AS and collagen deposition.Notably,the anti-fibrosis effect of Pae was achieved by regulating the gut microbiota.16S rRNA sequencing and LC-MS/MS data indicated that the relative abundance of SCFAs-producing bacteria and SCFAs production was increased.Additionally,Pae administration selectively up-regulated the frequency of regulatory T(Treg)cells as well as down-regulated the ratio of T helper type 17(Th17)cells in the spleen of AS mice,improving the Treg/Th17 balance.In addition,as expected,Pae intervention significantly down-regulate the mRNA expression levels of pro-inflammatory cytokines IL^(-1)β,IL-6,TNF-αand IL^(-1)7 in the aorta tissue,up-regulate the levels of anti-inflammatory factor IL^(-1)0,a marker of Treg cells.Finally,Pae′s intervention in the gut microbiota resulted in the restoration of the balance of Treg/Th17,which indirectly down-regulated the protein expression level of LOX and fibrosis-related indicators(MMP-2/9 and collagenⅠ/Ⅲ).CONCLUSION Pae attenuates vascular fibrosis in a gut microbiota-dependent manner.The underlying protective mechanism is associated with the improved Treg/Th17 balance in spleen mediated through the increased microbiota-derived SCFAs production.展开更多
Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were se...Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group(P<0.05).The maternal-fetal interface IL-4/IL-2,IL-10 / IL-2 of model group were balanced deviating to Th1,while the IL-4/IL-2,IL-10/IL-2 of progesterone group,Zishen Yutai pill group and joint group were balanced deviating to Th2,and joint group' deviation was better than progesterone group and Zishen Yutai pill group(P<0.05).Conclusions:Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion,which can obviously increase contents of maternal serums E2 and P,and regulate the Thl/Th2 balance with a remarkable effect.展开更多
Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU...Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU on complete Freund’s adjuvant(CFA)-induced rheumatoid arthritis(RA)had not been studied.In this study,we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema.Enzyme-linked immunosorbent assay(ELISA)was carried out to evaluate the plasma levels of immunoglobulin(Ig)G,IgE,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,receptor activator of nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG).Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints.The proportions of T helper type 1(Th1)and T helper type 2(Th2)cells of CD4+T lymphocyte subsets were analyzed by flow cytometry.The expression of Kelch-like ECHassociated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)was analyzed using real-time quantitative PCR(RT-qPCR)and western blotting assays.The present study demonstrated that SCU prevented CFA-induced RA,and inhibited the expression of inflammation factors,IgG,IgE,TNF-α,IL-1β,and IL-6.While SCU also reduced the RANKL level,it increased OPG expression in RA mice.The Th1/Th2 ratio was significantly lower in mice treated with SCU.Additionally,HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment.Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway.展开更多
Total glucosides of Rhizoma Smilacis Glabrae(RSG)are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells.In this study,w...Total glucosides of Rhizoma Smilacis Glabrae(RSG)are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells.In this study,we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis.Our findings revealed significant improvements upon administration of RSG in an imiquimod(IMQ)-induced psoriasis model.These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema,ulceration,and flaking.By transcriptome sequencing and T-cell flow sorting assay,we identified notable effects of RSG on the modulation of various cellular processes.Specifically,RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase cells.Furthermore,RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells.Of particular interest,we discovered thatβ-sitosterol,sitostenone,stigmasterol,smiglanin,and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells.In summary,our study highlights the therapeutic potential of RSG in the treatment of psoriasis,attributed to its ability to regulate the Th17/Treg balance.These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.展开更多
文摘Objective:To evaluate the effect of myricetin on ovalbumin(OVA)-induced allergic rhinitis in mice.Methods:Mice were sensitized and challenged using OVA(5%,500 mL)intraperitoneally and intranasally,respectively,on an alternative day for 14 days,followed by administration of myricetin(50,100,and 200 mg/kg)till day 21.Nasal symptoms,biochemical parameters,protein expressions,and histopathology were observed.Results:OVA-induced increased nasal symptoms including rubbing,sneezing,and discharge were significantly reduced by myricetin(100and 200 mg/kg)(P<0.05).Myricetin also protected against histamine challenge and attenuated elevated serum immunoglobulin E(IgE;total and OVA-specific),total IgG1,andβ-hexosaminidase levels,as well as leukotriene C4 and interleukins levels in nasal lavage fluid(P<0.05).Western blot analysis showed that myricetin significantly upregulated the protein expression of T-box expressed in T cells,while downregulating the protein expression of GATA binding protein 3,NF-κB,and IκB-α(P<0.05).Additionally,OVA-induced histopathological abberations in the nasal mucosa was markedly ameliorated by myricetin treatment(P<0.05).Conclusions:Myricetin exerts anti-allergic effects against OVAinduced allergic rhinitis via regulating Th1/Th2 balance.
基金National Natural Science Foundation of China (No.81960887)Innovation Project of Guangxi Graduate Education (No.YCXJ2021119)。
文摘Objective:To evaluate the therapeutic effect of Glycyrrhetinic Acid on cough variant asthma(CVA)mice and to investigate the possible mechanism in reducing lung inflammation.Methods:48 young female Balb/c mice were divided into Control,CVA,Prednisone Acetate,Glycyrrhetinic Acid high-dose,Glycyrrhetinic Acid middle-dose and Glycyrrhetinic Acid lowdose groups randomly,with 8 mice in each group.The CVA mice model was established by ovalbumin(OVA)sensitization and OVA challenge,the animal asthma behavior was observed after drug administration,and the index of the lung of mice were recorded.The level of OVAsIgE in the bronchoalveolar lavage fluid(BALF)was tested by ELISA.The pathological changes of the lung tissue were observed by Hematoxylin and Eosin(H&E)staining.The protein expressions of T-bet,IFN-γ,Gata3,IL-4 and IL-13 in the lung tissue were determined by Western blot.Results:Compared with the CVA group,the index of lung of mice,the OVA-sIgE level in BALF and expression levels of Th2-related factor in the lung tissue of mice in Prednisone Acetate and Glycyrrhetinic Acid groups were significantly decreased(P<0.05 or P<0.01),the infiltration of inflammatory cells in the lung tissue was reduced,while expressions of Th1-related factor in the lung tissue was significantly increased(P<0.05 or P<0.01).Conclusion:Glycyrrhetinic acid has therapeutic effect on CVA mice,the underlying mechanism of Glycyrrhetinic acid alleviating lung impairment and airway inflammation may be associated with mediating the Th1/Th2 imbalance in the lung tissue.
文摘Objective:To study the influence of budesonide and salbutamol atomization inhalation on Th17/Treg balance in patients with bronchial asthma and its correlation with airway remodeling.Methods:A total of 90 patients with bronchial asthma who received systemic treatment in our hospital between July 2013 and April 2016 were divided into control group (n=45) and observation group (n=45) according to random number table. Patients in the control group were treated with salbutamol atomization inhalation alone while those in observation group were treated with budesonide and salbutamol atomization inhalation. The Th17/Treg ratio in peripheral blood as well as serum contents of airway remodeling-related indicators was compared between two groups before and after treatment. The correlation between Th17/Treg balance and airway remodeling in patients with bronchial asthma was detected by Pearson test. Results:Before treatment, the differences in peripheral blood Th17/Treg ratio as well as serum contents of inflammatory mediators, growth factor indexes and collagen metabolism indexes were not statistically significant between two groups of patients. After treatment, peripheral blood Th17/Treg ratio in observation group was lower than that in control group, serum CRP, IL-8, IL-13 and TNF- contents in observation group were lower than those in control group, serum PDGF-BB, b-FGF and VEGF contents in observation group were lower than those in control group, and serum HA, PCⅢ and LN contents in observation group were lower than those in control group. The Th17/Treg ratio in patients with bronchial asthma after treatment was positively correlated with the levels of airway remodeling-related indexes.Conclusion:Budesonide combined with salbutamol atomization inhalation can optimize the Th17/Treg balance in patients with bronchial asthma, and Th17/Treg is directly correlated to the degree of airway remodeling.
基金Shandong natural science foundation(No.ZR2019MH083)National Famous and Old Chinese Medicine Expert Li Guangwen Inheritance StudioWang Dongmei Shandong Province Famous and Old Chinese Medicine Expert Inheritance Studio。
文摘Objective:Explore the role of Th1/Th2 balance in the pathogenesis of primary dysmenorrhea through study the effect of Th1/Th2 balance drift on serum prostaglandin F_(2α),prostaglandin,6-keto-prostaglandin F_(1α),TXB2,COX-2,AVP and OT in Primary Dysmenorrhea Rats with cold coagulation and blood stasis syndrome.Method:The rat model of primary dysmenorrhea with cold coagulation and blood stasis syndrome was established.On the basis of this model,Th1 shift model and Th2 shift model were established.The rats were divided into blank group,model group,Th1 shifting group and Th2 shifting group.The writhing reaction of rats in each group was compared,and the contents of PGF_(2α),PGE_(2),6-keto-PGF_(1α),TXB2,COX-2,AVP and OT in serum were detected.Results:Writhing latency:There was no significant difference between Th1 and Th2 shifting groups(P>0.05),Th2 shifting group was shorter than Th1 shifting group(P<0.05).Writhing times in 30 minutes:Compared with the model group,the writhing times of Th1 shifting group decreased significantly(P<0.01),while Th2 shifting group increased significantly(P<0.01).Compared with the blank group,the contents of PGF_(2α),TXB2,COX-2,AVP and OT were increased(P<0.05,P<0.01),and the contents of 6-keto-PGF_(1α)and PGE_(2)were decreased(P<0.01).Compared with the model group,the contents of PGF_(2α),TXB2,COX-2 and AVP in Th1 shifting group were decreased(P<0.05,P<0.01),and the contents of 6-keto-PGF_(1α)and PGE_(2)were increased(P<0.01),while the contents of PGF_(2α),TXB2,COX-2,AVP and OT in Th2 shifting group were increased(P<0.01),and the contents of 6-keto-PGF_(1α)and PGE_(2)were decreased(P<0.01).Conclusion:The intervention of Th1/Th2 cell balance on the expression of PGF_(2α),PGE_(2),6-keto-PGF_(1α),TXB2,COX-2,AVP and OT may be one of the pathogenesis of PD with cold coagulation and blood stasis syndrome.
基金supported by the National Natural Science Foundation of China(No.30671761)
文摘The essential effect of vitamin A on immune function occurs through various mechanisms including direct effect on ThloTh2 balance modulation. However, it is unclear whether or not vitamin A can regulate Thl-Th2 balance under a strong Thl-polarizing condition. Therefore, the purpose of our study was to examine the effect of vitamin A metabolite allotrans retinoic acid （ATRA） on ThloTh2 differentiation in CD4~ T cells under GATA-3 deficiency, which can induce Thl-polarizing condition. In the present study, GATA-3 deficiency T cells were induced by siRNA and checked by real-time quantitative PCR and western blot. GATA-3 deficiency CD4＋ T cells and normal CD4＋ T were treated for 48 h with or without ATRA.
基金National Natural Science Foundation of China(81773937)。
文摘OBJECTIVE Atherosclerosis(AS)is a chronic inflammatory disease characterized by the accumulation of lipids,vascular fibrosis,and inflammation.Paeonol(Pae)is a natural phenolic compounds isolated from a traditional Chinese medicine,Cortex Moutan,which exhibits anti-AS effects.Our previous work demonstrated that gut microbiota plays an important role during AS treatment as it affects the efficacy of Pae.However,the mechanism of Pae in protecting against vascular fibrosis as related to gut microbiota has yet to be elucidated.To investigate the anti-fibrosis effect of Pae on AS mice and demonstrate the underlying gut microbiota-dependent mechanism.METHODS ApoE-/-mice were fed with high-fat-diet(HFD)to replicate the AS model.HE and Masson staining were used to observe the plaque formation and collagen deposition.Gut microbiota alteration and short-chain fatty acids(SCFAs)production were analyzed through 16S rRNA sequencing and LC-MS/MS.The frequency of immune cells in spleen were phenotyped by flow cytometry.The mRNA expression of aortic inflammatory cytokines were detected by qRT-PCR.The protein expression of LOX and fibrosis related indicators were examined by Western blotting.RESULTS Pae restricted the development of AS and collagen deposition.Notably,the anti-fibrosis effect of Pae was achieved by regulating the gut microbiota.16S rRNA sequencing and LC-MS/MS data indicated that the relative abundance of SCFAs-producing bacteria and SCFAs production was increased.Additionally,Pae administration selectively up-regulated the frequency of regulatory T(Treg)cells as well as down-regulated the ratio of T helper type 17(Th17)cells in the spleen of AS mice,improving the Treg/Th17 balance.In addition,as expected,Pae intervention significantly down-regulate the mRNA expression levels of pro-inflammatory cytokines IL^(-1)β,IL-6,TNF-αand IL^(-1)7 in the aorta tissue,up-regulate the levels of anti-inflammatory factor IL^(-1)0,a marker of Treg cells.Finally,Pae′s intervention in the gut microbiota resulted in the restoration of the balance of Treg/Th17,which indirectly down-regulated the protein expression level of LOX and fibrosis-related indicators(MMP-2/9 and collagenⅠ/Ⅲ).CONCLUSION Pae attenuates vascular fibrosis in a gut microbiota-dependent manner.The underlying protective mechanism is associated with the improved Treg/Th17 balance in spleen mediated through the increased microbiota-derived SCFAs production.
基金supported by Natural Sciences Fund of Zhejiang Province(grant number:LY14H040011)Subject of Zhejiang Provincial Administration of traditional Chinese Medicine(grant number:2013ZB058)
文摘Objective:To observe preventive and therapeutic effects and the mechanism of actions on Zishen Yutai pill combined with progesterone on threatened abortion in rats.Methods:After pregnancy,50 SPF female SD rats were selected and divided into control group,model group,progesterone group,Zishen Yutai pill group,and progesterone plus Zishen Yutai pill group(combination group),with 10 rats in each group.The rats of control group and abortion model group were lavaged with 2 mL/kg normal saline on pregnancy day 1 for continuous 10 days.Rats in Zishen Yutai pill group were given 1.575 g/kg/d of Zishen Yutai pill for intragastric administration for continuous 10 days.Rats in progesterone group were given intramuscular injection treatment of 0.1 mL/d progestin,continuous for 10 days.Rats in combination group were given injection therapy of aqueous solution of Zishen Yutai pill for continuous 10 days,and other treatments were the same as previous two groups.Abortion model were established then and live births,numbers of abortion and average rate of abortion were compared between the five groups.Peripheral blood was collected to detect the estradiol(E2) and progestational hormone(P),and obtain ratio of Th1/Th2 cytokines(IL-2,INF-γ,IL-4,IL-10).Results:Significant more live births of rats were found in the control group compared with other four groups(P<0.05).The numbers of live births of the rats in abortion model group were significantly less than that of progesterone group,Zishen Yutai pill group and joint group(P<0.05).The numbers of live births of rats in joint group were significant more than that of progesterone group and Zishen Yutai pill group.The serum E2 level of P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were significant higher than that of abortion model group(P<0.05).Serum levels of E2 and P of rats in the control group,progesterone group,Zishen Yutai pill group and joint group were not significant different(P>0.05) but these levels in the control group and Zishen Yutai pill group were significant lower than that of progesterone group and joint group(P<0.05).The maternal-fetal interface IL-4/IL-2,IL-10 / IL-2 of model group were balanced deviating to Th1,while the IL-4/IL-2,IL-10/IL-2 of progesterone group,Zishen Yutai pill group and joint group were balanced deviating to Th2,and joint group' deviation was better than progesterone group and Zishen Yutai pill group(P<0.05).Conclusions:Zishen Yutai pill combined with progesterone has a significant control effect for threatened abortion,which can obviously increase contents of maternal serums E2 and P,and regulate the Thl/Th2 balance with a remarkable effect.
文摘Scutellarin(SCU)is a herbal flavonoid glucuronide with multiple pharmacological activities,including antioxidant,anti-inflammation,vascular relaxation,anti-platelet,and myocardial protection.However,the effect of SCU on complete Freund’s adjuvant(CFA)-induced rheumatoid arthritis(RA)had not been studied.In this study,we investigated the beneficial effects of SCU in the CFA-induced RA mice model and the anti-arthritic activity was evaluated by paw edema.Enzyme-linked immunosorbent assay(ELISA)was carried out to evaluate the plasma levels of immunoglobulin(Ig)G,IgE,tumor necrosis factor(TNF)-α,interleukin(IL)-1β,IL-6,receptor activator of nuclear factor-κB ligand(RANKL),and osteoprotegerin(OPG).Histological slides were prepared from the harvested paws of mice to determine the pathological changes in the joints.The proportions of T helper type 1(Th1)and T helper type 2(Th2)cells of CD4+T lymphocyte subsets were analyzed by flow cytometry.The expression of Kelch-like ECHassociated protein 1(Keap1),nuclear factor erythroid 2-related factor 2(Nrf2),and heme oxygenase-1(HO-1)was analyzed using real-time quantitative PCR(RT-qPCR)and western blotting assays.The present study demonstrated that SCU prevented CFA-induced RA,and inhibited the expression of inflammation factors,IgG,IgE,TNF-α,IL-1β,and IL-6.While SCU also reduced the RANKL level,it increased OPG expression in RA mice.The Th1/Th2 ratio was significantly lower in mice treated with SCU.Additionally,HO-1 expression was reduced while the expression of Keap1 and Nrf2 was elevated following SCU treatment.Results provide preliminary evidence to employ SCU in arthritis treatment which might be related to the regulation of Th1/Th2 balance and the Keap1/Nrf2/HO-1 pathway.
基金supported by the National Natural Science Foundation of China(Nos.82074114,81973562 and 81773995),the Scholar of the 14th batch of“Six Talents Peak”highlevel talent selection(No.SWYY-094)the“Double First-Class”University project(No.CPU2018GY33).
文摘Total glucosides of Rhizoma Smilacis Glabrae(RSG)are selective immunosuppressants that exhibit primary efficacy in the treatment of rheumatoid arthritis through targeted inhibition of activated T cells.In this study,we aimed to investigate the potential application of RSG in the treatment of psoriasis and elucidate its mechanism of action and material basis.Our findings revealed significant improvements upon administration of RSG in an imiquimod(IMQ)-induced psoriasis model.These improvements were characterized by a remarkable increase in the number of tail scales in mice and a substantial amelioration of skin erythema,ulceration,and flaking.By transcriptome sequencing and T-cell flow sorting assay,we identified notable effects of RSG on the modulation of various cellular processes.Specifically,RSG prominently down-regulated the Th17/Treg ratio in damaged skin tissues and reduced the proportion of G2 phase cells.Furthermore,RSG exhibited a stimulatory effect on the proliferation and differentiation of epithelial cells.Of particular interest,we discovered thatβ-sitosterol,sitostenone,stigmasterol,smiglanin,and cinchonain Ib displayed potent inhibitory effects on the IL-17-mediated inflammatory response in HaCaT cells.In summary,our study highlights the therapeutic potential of RSG in the treatment of psoriasis,attributed to its ability to regulate the Th17/Treg balance.These findings contribute to the development of new indications for RSG and provide a solid theoretical foundation for further exploration in this field.
