Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'phys...Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'physical status.However,its mechanism of function has not been investigated.Metabolic perturbations have been associated with RA,and targeting the metabolic profile is one of the ways to manage the disease.The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factorα(hTNF-α)transgenic arthritic model mice.Methods hTNF-αtransgenic arthritic model mice were divided into the control group and the GNYD group with six mice in each group.After 8 weeks of treatment,liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry analysis.Significantly regulated metabolites by GNYD treatment were first identified,followed by Kyoto Encyclopedia of Genes and Genomes pathway and network analysis.Results A total of 126 metabolites were detected in the liver.Compared with the control group,17 metabolites in the GNYD group were significantly altered.Specifically,thiamine,gamma-L-glutamyl-L-valine,pantothenic acid,pyridoxal(vitamin B6),succinic acid,uridine 5′-diphospho-glucuronic acid,uridine,allantoic acid,N-acetyl-D-glucosamine,nicotinamide ribotide,and N2,N2-dimethylguanosine were down-regulated by GNYD treatment,whereas isobutyrylglycine,N-acetylcadaverine,N-carbamoyl-L-aspartic acid,L-anserine,creatinine,and cis-4-hydroxy-D-proline were up-regulated.Six metabolic pathways were significantly altered including the alanine,aspartate,and glutamate metabolism;pyrimidine metabolism;thiamine metabolism;amino sugar and nucleotide sugar metabolism;pantothenate and CoA biosynthesis;and citrate cycle.Integrative metabolic network analysis suggested the possibility of GNYD having both positive and negative effects on RA through the suppression of angiogenesis and the promotion of leukocyte extravasation into the synovium,respectively.Conclusions GNYD can modulate the hepatic metabolism of hTNF-αtransgenic arthritic model mice.Further optimization of this decoction may lead to better therapeutic effects on RA patients.展开更多
Objective： To observe the effect of moxibustion on the expressions of tumor necrosis factor-α（TNF-α） and nuclear transcription factor kappa B（NF-κB） proteins in ankle joints of rats with rheumatoid arthritis...Objective： To observe the effect of moxibustion on the expressions of tumor necrosis factor-α（TNF-α） and nuclear transcription factor kappa B（NF-κB） proteins in ankle joints of rats with rheumatoid arthritis（RA）, and to explore the anti-inflammatory mechanism of moxibustion in the treatment of RA. Methods： Adjuvant arthritis（AA） rat models were induced and used as rat models of RA. Rats were randomly divided into a normal group, a model group, a moxibustion group and a saline group. Rats in the normal and model groups were not treated; rats in the moxibustion group accepted treatment by moxibustion at Zusanli（ST 36） and Shenshu（BL 23） after modeling; rats in the saline group were injected with 0.15 mL saline to the bottom of the left hind paw and had no other treatments. Hematoxylin-eosin（HE） staining was used to observe the histopathological changes of rats＇ ankle joints under light microscope. Immunohistochemistry was used to observe the expressions of TNF-α and NF-κB in ankle joints of rats. Results： Compared with the normal group, the rats＇ ankle joints in the model group showed disorganization, joint surface defect, and significantly increased mean optical density（MOD） of TNF-α and NF-κB（all P〈0.05）. After moxibustion treatment, rats in the moxibustion group showed repaired ankle tissues, smooth joint surface without defects, decreased MOD of TNF-α and NF-κB than those in the model group（all P〈0.05）. Rats in the saline group had no damage to ankle joints, while TNF-α and NF-κB were significantly different from those in the model group（P〈0.05）. Conclusion： Moxibustion could down-regulate the expressions of NF-κB and TNF-α protein in ankle joints of RA rats, and produce an anti-inflammatory effect to promote tissue repair.展开更多
Objective:To observe the effects of moxibustion on serum levels of interleukin(IL)-6,IL-8 and tumor necrosis factor-α(TNF-α),and to explore the effects of moxibustion on inflammatory damaging factors in experimental...Objective:To observe the effects of moxibustion on serum levels of interleukin(IL)-6,IL-8 and tumor necrosis factor-α(TNF-α),and to explore the effects of moxibustion on inflammatory damaging factors in experimental rheumatoid arthritis(RA)model rats;the relationship between the therapeutic effect of moxibustion on RA and the change in the Toll-like receptor(TLR)signaling pathway was analyzed using Toll-like receptor 4(TLR4)antagonists and agonists.Methods:Fifty Sprague-Dawley(SD)rats were divided into a normal group,a model group,a moxibustion group,a moxibustion plus TLR4 agonist group(agonist group)and a moxibustion plus TLR4 antagonist group(antagonist group)according to the random number table,with 10 rats in each group.Except the normal group,rats in the other four groups were subjected to model preparation with the wind,cold and wet environmental factors plus Freund's complete adjuvant(FCA).Rats in the normal and model groups were not treated;rats in the moxibustion,agonist and antagonist groups started to be treated with the moxibustion(cigarette-type moxa)at bilateral Shenshu(BL 23)and Zusanli(ST 36)from the 4th day after the successful modeling,for 20 min each time with a total of 10 d.Rats in the agonist and the antagonist groups were injected with TLR4 agonist or antagonist[0.1 mg/(kg*bw)]via the tail vein 30 min before moxibustion.The concentrations of serum IL-6,IL-8 and TNF-αin each group were determined by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the normal group,in the model group,the rat's right hind paw swelling was significantly obvious(P<0.01);there was a lot of inflammatory infiltration in the synovial tissues,the surface of the synovial membrane was unsmooth,the synovial membrane was hyperplasia and thicker,and the serum IL-6,IL-8 and TNF-αconcentrations increased significantly(P<0.05).Compared with the model group,the paw swelling degrees of the rats in the moxibustion,the agonist and the antagonist groups reduced significantly(all P<0.01);the swelling degree in the antagonist group was milder than that in the agonist group,but the between-group difference was not statistically significant(P>0.05);inflammatory infiltration and synovial membrane hyperplasia in the synovial tissues of the moxibustion group and the antagonist group were all relieved differently;the decrease of synovial layer number in the moxibustion group was more obvious,and there were no obvious improvements in inflammatory infiltration and synovial thickness in the agonist group;the concentrations of IL-6,IL-8 and TNF-αin the moxibustion group were decreased,and the differences in the IL-6 and TNF-αconcentrations were statistically significant(all P<0.01);there was no significant between-group difference in the IL-8 concentration(P>0.05);the concentrations of serum IL-8 and TNF-αin the agonist group increased significantly(both P<0.01),while the IL-6 concentration decreased without significant difference(P>0.05);the concentrations of IL-6 and IL-8 in the antagonist group decreased but the between-group differences were statistically insignificant(both P>0.05);and the TNF-αconcentration significantly increased(P<0.05).Compared with the moxibustion group,IL-6,IL-8 and TNF-αconcentrations increased in the agonist group,and the differences in the IL-8 and TNF-αconcentrations were statistically significant(both P<0.01);the concentrations of IL-6,IL-8 and TNF-αincreased in the antagonist group,and the differences in the IL-6 and TNF-αconcentrations were statistically significant(both P<0.01);there was no significant difference in the IL-8 concentration between the groups(P>0.05).The serum levels of IL-6,IL-8 and TNF-αin the antagonist group were lower than those in the agonist group(all P<0.05).Conclusion:Moxibustion at Shenshu(BL 23)and Zusanli(ST 36)can reduce the joint swelling degree and inflammation in synovial tissue of RA model rats,decrease the serum levels of IL-6,IL-8 and TNF-αin RA model rats;the decreases of IL-6 and TNF-αare more significant than the decrease of IL8;TLR4 agonist and antagonist can significantly attenuate the effect of moxibustion in inhibiting releases of IL-6,IL-8 and TNF-α,so that the change in TLR signaling pathway affects the effect of moxibustion in inhibiting the releases of IL-6,IL-8 and TNF-α.展开更多
基金supported by the Scientific Research Project of Guangdong Province Traditional Chinese Medicine Bureau(20201229)and China Postdoctoral Science Foundation Project(2021M701438).
文摘Objective Gancao Nourish-Yin Decoction(GNYD)has been applied to clinical rheumatoid arthritis(RA)patients,and it had shown effectiveness not only in disease activity controlling but also in improving patients'physical status.However,its mechanism of function has not been investigated.Metabolic perturbations have been associated with RA,and targeting the metabolic profile is one of the ways to manage the disease.The aim of this study is to observe the effect of GNYD on metabolic changes of human tumor necrosis factorα(hTNF-α)transgenic arthritic model mice.Methods hTNF-αtransgenic arthritic model mice were divided into the control group and the GNYD group with six mice in each group.After 8 weeks of treatment,liver tissues of mice in both groups were obtained for liquid chromatography-mass spectrometry analysis.Significantly regulated metabolites by GNYD treatment were first identified,followed by Kyoto Encyclopedia of Genes and Genomes pathway and network analysis.Results A total of 126 metabolites were detected in the liver.Compared with the control group,17 metabolites in the GNYD group were significantly altered.Specifically,thiamine,gamma-L-glutamyl-L-valine,pantothenic acid,pyridoxal(vitamin B6),succinic acid,uridine 5′-diphospho-glucuronic acid,uridine,allantoic acid,N-acetyl-D-glucosamine,nicotinamide ribotide,and N2,N2-dimethylguanosine were down-regulated by GNYD treatment,whereas isobutyrylglycine,N-acetylcadaverine,N-carbamoyl-L-aspartic acid,L-anserine,creatinine,and cis-4-hydroxy-D-proline were up-regulated.Six metabolic pathways were significantly altered including the alanine,aspartate,and glutamate metabolism;pyrimidine metabolism;thiamine metabolism;amino sugar and nucleotide sugar metabolism;pantothenate and CoA biosynthesis;and citrate cycle.Integrative metabolic network analysis suggested the possibility of GNYD having both positive and negative effects on RA through the suppression of angiogenesis and the promotion of leukocyte extravasation into the synovium,respectively.Conclusions GNYD can modulate the hepatic metabolism of hTNF-αtransgenic arthritic model mice.Further optimization of this decoction may lead to better therapeutic effects on RA patients.
基金supported by Youth Project of Anhui Provincial Natural Science Foundation,No.1508085QH160Youth Scientific Research Fund Project of Anhui University of Chinese Medicine,No.2014qn004+1 种基金2016 Undergraduate Innovation and Entrepreneurship Training Program of Anhui University of Chinese Medicine,No.2016097Innovation Team Project of Scientific Research Platform for Universities in Anhui Province,No.2015TD033~~
文摘Objective： To observe the effect of moxibustion on the expressions of tumor necrosis factor-α（TNF-α） and nuclear transcription factor kappa B（NF-κB） proteins in ankle joints of rats with rheumatoid arthritis（RA）, and to explore the anti-inflammatory mechanism of moxibustion in the treatment of RA. Methods： Adjuvant arthritis（AA） rat models were induced and used as rat models of RA. Rats were randomly divided into a normal group, a model group, a moxibustion group and a saline group. Rats in the normal and model groups were not treated; rats in the moxibustion group accepted treatment by moxibustion at Zusanli（ST 36） and Shenshu（BL 23） after modeling; rats in the saline group were injected with 0.15 mL saline to the bottom of the left hind paw and had no other treatments. Hematoxylin-eosin（HE） staining was used to observe the histopathological changes of rats＇ ankle joints under light microscope. Immunohistochemistry was used to observe the expressions of TNF-α and NF-κB in ankle joints of rats. Results： Compared with the normal group, the rats＇ ankle joints in the model group showed disorganization, joint surface defect, and significantly increased mean optical density（MOD） of TNF-α and NF-κB（all P〈0.05）. After moxibustion treatment, rats in the moxibustion group showed repaired ankle tissues, smooth joint surface without defects, decreased MOD of TNF-α and NF-κB than those in the model group（all P〈0.05）. Rats in the saline group had no damage to ankle joints, while TNF-α and NF-κB were significantly different from those in the model group（P〈0.05）. Conclusion： Moxibustion could down-regulate the expressions of NF-κB and TNF-α protein in ankle joints of RA rats, and produce an anti-inflammatory effect to promote tissue repair.
文摘Objective:To observe the effects of moxibustion on serum levels of interleukin(IL)-6,IL-8 and tumor necrosis factor-α(TNF-α),and to explore the effects of moxibustion on inflammatory damaging factors in experimental rheumatoid arthritis(RA)model rats;the relationship between the therapeutic effect of moxibustion on RA and the change in the Toll-like receptor(TLR)signaling pathway was analyzed using Toll-like receptor 4(TLR4)antagonists and agonists.Methods:Fifty Sprague-Dawley(SD)rats were divided into a normal group,a model group,a moxibustion group,a moxibustion plus TLR4 agonist group(agonist group)and a moxibustion plus TLR4 antagonist group(antagonist group)according to the random number table,with 10 rats in each group.Except the normal group,rats in the other four groups were subjected to model preparation with the wind,cold and wet environmental factors plus Freund's complete adjuvant(FCA).Rats in the normal and model groups were not treated;rats in the moxibustion,agonist and antagonist groups started to be treated with the moxibustion(cigarette-type moxa)at bilateral Shenshu(BL 23)and Zusanli(ST 36)from the 4th day after the successful modeling,for 20 min each time with a total of 10 d.Rats in the agonist and the antagonist groups were injected with TLR4 agonist or antagonist[0.1 mg/(kg*bw)]via the tail vein 30 min before moxibustion.The concentrations of serum IL-6,IL-8 and TNF-αin each group were determined by enzyme-linked immunosorbent assay(ELISA).Results:Compared with the normal group,in the model group,the rat's right hind paw swelling was significantly obvious(P<0.01);there was a lot of inflammatory infiltration in the synovial tissues,the surface of the synovial membrane was unsmooth,the synovial membrane was hyperplasia and thicker,and the serum IL-6,IL-8 and TNF-αconcentrations increased significantly(P<0.05).Compared with the model group,the paw swelling degrees of the rats in the moxibustion,the agonist and the antagonist groups reduced significantly(all P<0.01);the swelling degree in the antagonist group was milder than that in the agonist group,but the between-group difference was not statistically significant(P>0.05);inflammatory infiltration and synovial membrane hyperplasia in the synovial tissues of the moxibustion group and the antagonist group were all relieved differently;the decrease of synovial layer number in the moxibustion group was more obvious,and there were no obvious improvements in inflammatory infiltration and synovial thickness in the agonist group;the concentrations of IL-6,IL-8 and TNF-αin the moxibustion group were decreased,and the differences in the IL-6 and TNF-αconcentrations were statistically significant(all P<0.01);there was no significant between-group difference in the IL-8 concentration(P>0.05);the concentrations of serum IL-8 and TNF-αin the agonist group increased significantly(both P<0.01),while the IL-6 concentration decreased without significant difference(P>0.05);the concentrations of IL-6 and IL-8 in the antagonist group decreased but the between-group differences were statistically insignificant(both P>0.05);and the TNF-αconcentration significantly increased(P<0.05).Compared with the moxibustion group,IL-6,IL-8 and TNF-αconcentrations increased in the agonist group,and the differences in the IL-8 and TNF-αconcentrations were statistically significant(both P<0.01);the concentrations of IL-6,IL-8 and TNF-αincreased in the antagonist group,and the differences in the IL-6 and TNF-αconcentrations were statistically significant(both P<0.01);there was no significant difference in the IL-8 concentration between the groups(P>0.05).The serum levels of IL-6,IL-8 and TNF-αin the antagonist group were lower than those in the agonist group(all P<0.05).Conclusion:Moxibustion at Shenshu(BL 23)and Zusanli(ST 36)can reduce the joint swelling degree and inflammation in synovial tissue of RA model rats,decrease the serum levels of IL-6,IL-8 and TNF-αin RA model rats;the decreases of IL-6 and TNF-αare more significant than the decrease of IL8;TLR4 agonist and antagonist can significantly attenuate the effect of moxibustion in inhibiting releases of IL-6,IL-8 and TNF-α,so that the change in TLR signaling pathway affects the effect of moxibustion in inhibiting the releases of IL-6,IL-8 and TNF-α.
