AIM:To determine the molecular mechanisms of Shugan decoction(SGD) in the regulation of colonic motility and visceral hyperalgesia(VHL) in irritable bowel syndrome(IBS).METHODS:The chemical compounds contained in SGD ...AIM:To determine the molecular mechanisms of Shugan decoction(SGD) in the regulation of colonic motility and visceral hyperalgesia(VHL) in irritable bowel syndrome(IBS).METHODS:The chemical compounds contained in SGD were measured by high-performance liquid chromatography.A rat model of IBS was induced by chronic water avoidance stress(WAS).The number of fecal pellets was counted after WAS and the pain pressure threshold was measured by colorectal distension.Morphological changes in colonic mucosa were detected by hematoxylin-eosin staining.The contents of tumor necrosis factor(TNF)-αin colonic tissue and calcitonin-gene-related peptide(CGRP)in serum were measured by ELISA.The protein expression of serotonin[5-hydroxytryptamide(5-HT)],serotonin transporter(SERT),chromogranin A(Cg A)and CGRP incolon tissue was measured by immunohistochemistry.RESULTS:SGD inhibited colonic motility dysfunction and VHL in rats with IBS.Blockers of transient receptor potential(TRP)vanilloid 1(TRPV1)(Ruthenium Red)and TRP ankyrin-1(TRPA1)(HC-030031)and activator of protease-activated receptor(PAR)4 increased the pain pressure threshold,whereas activators of PAR2and TRPV4 decreased the pain pressure threshold in rats with IBS.The effect of SGD on pain pressure threshold in these rats was abolished by activators of TRPV1(capsaicin),TRPV4(RN1747),TRPA1(Polygodial)and PAR2(AC55541).In addition,CGRP levels in serum and colonic tissue were both increased in these rats.TNF-αlevel in colonic tissue was also significantly upregulated.However,the levels of 5-HT,SERT and Cg A in colonic tissue were decreased.All these pathological changes in rats with IBS were attenuated by SGD.CONCLUSION:SGD alleviated VHL and attenuated colon motility in IBS,partly by regulating TRPV1,TRPV4,TRPA1,PAR2,5-HT,Cg A and SERT,and reducing CGRP and TNF-αlevel.展开更多
AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for ...AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress(WAS)test.Untreated model rats were exposed to chronic(1 h/d for 10 d consecutive)WAS conditions;experimental treatment model rats were administered with intragastric SGD at1 h before WAS on consecutive days 4-10(low-dose:0.1g/mL;mid-dose:0.2 g/mL;high-dose:0.4 g/mL);control treatment model rats were similarly administered with the irritable bowel syndrome drug,dicetel(0.0042g/mL);untreated normal control rats received no drug and were not subjected to the WAS test.At the end of the 10-d WAS testing period,a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex(AWR)to colorectal balloon-induced distension(at 5 mmHg increments)to determine the pain pressure threshold(PPT,evidenced by pain behavior).Subsequently,the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity(transient receptor potential vanilloid 1,TRPV1)and sustained visceral hyperalgesia(substance P,SP)by immunohistochemistry and real-time polymerase chain reaction.Inter-group differences were assessed by paired t test or repeated measures analysis of variance.RESULTS:The WAS test successfully induced visceral hypersensitivity,as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group(190.4±3.48 mmHg vs 224.0±4.99 mmHg,P<0.001).SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT(212.5±2.54,216.5±3.50 and 217.7±2.83 mmHg respectively,all P<0.001);however,the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT(198.3±1.78 mmHg,P>0.05).These trends corresponded to the differential expressions observed for both TRPV1 protein(mid-dose:1.64±0.08 and high-dose:1.69±0.12 vs untreated model:3.65±0.32,P<0.001)and mRNA(0.44±0.16 and0.15±0.03 vs 1.39±0.15,P<0.001)and SP protein(0.99±0.20 and 1.03±0.23 vs 2.03±0.12,P<0.01)and mRNA(1.64±0.19 and 1.32±0.14 vs 2.60±0.33,P<0.05).These differential expressions of TRPV1 and SP related to mid-and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment.No signs of overt damage to the rat system were observed for any of the SGD dosages.CONCLUSION:Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats,and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues.展开更多
Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six ...Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six groups:a normal control group,a model group,apositive control(domperidone)group and low-,middle-and high-dose CSD groups.A rat model of FD was established by constantly squeezing their tails.The rats were administered CSD(0.16g/mL,0.32g/mL,0.64g/mL)or domperidone(0.3 g/L)via intragastric gavage for four weeks.The gastric emptying rate was detected at 4 weeks post-administration.Apoptosis of GSMCs was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and the mitochondrial morphology was observed by transmission electron microscopy.The expression of Bcl-2and Bax was measured by immunohistochemistry.Results:FD resulted in marked reduction of gastric emptying rate,severe gastric tissue damage and mitochondria injury,but were reversed by CSD treatment(P<0.05).The apoptosis-induced protein Bax was markedly down-regulated by CSD,whereas the expression of the anti-apoptotic Bcl-2 protein was notably increased(P<0.05).Furthermore,CSD could protect the FD rats against GSMCs apoptosis manifested by a decreased in TUNEL-positive cells(P<0.05).Conclusion:CSD could alleviate GSMCs apoptosis in FD rats,possibly by the modulation of Bcl-2 and Bax expression,and the suppression of mitochondria injury.展开更多
Objective:To explore the molecular biological mechanism of Shugan Jianpi Decoction in treating depression-related breast cancer based on network pharmacology.Methods:The active compounds of Shugan Jianpi Decoction wer...Objective:To explore the molecular biological mechanism of Shugan Jianpi Decoction in treating depression-related breast cancer based on network pharmacology.Methods:The active compounds of Shugan Jianpi Decoction were explored to obtain their drug targets,and the venny network,"TCM-component-target"network,PPI network,"pathway-gene"network,GO and KEGG enrichment results were constructed using relevant softwares.Results:A total of 121 active ingredients,250 genes,2357 GO functions and 184 KEGG pathways were obtained.Conclusion:The active ingredients of Shugan Jianpi Decoction are quercetinll、kaempferol、luteolin、naringenin.The key targets are MAPK1,MAPK3,RELA,and AKT1.GO functions include cellular response to hormone stimulus、cellular response to lipid、cellular response to oxidative stress and so on.KEGG mainly involves PI3K-Akt,microRNAs,and FoxO signaling pathways.This study preliminarily explores the molecular biological mechanism of Shugan Jianpi Decoction in the treatment of depression-related breast cancer,and speculates that it mainly acts by arresting the cell cycle,inhibiting cancer cell proliferation,mediating cancer cell apoptosis,and preventing its recurrence and metastasis,which provides new evidence and new direction for subsequent clinical application and experimental research.展开更多
Chronic calculous cholecystitis is a common clinical medical disease,which is classified as"hypochondriac pain"in traditional Chinese medicine(TCM).It is caused by liver failure and stagnation of liver qi.Th...Chronic calculous cholecystitis is a common clinical medical disease,which is classified as"hypochondriac pain"in traditional Chinese medicine(TCM).It is caused by liver failure and stagnation of liver qi.Therefore,the method of Soothing the liver and promoting bile flow is often used for regulating and harmonizing qi and blood.This paper discusses its mechanism of action,and points out that Shugan Lidan decoction has great effect on the treatment of chronic calculous cholecystitis,especially in the early treatment of the disease and delaying the progress of the disease,which provides help for the clinical treatment of chronic calculous cholecystitis.展开更多
基金Supported by Innovation Program of the Shanghai Municipal Education Commission,No.12YZ065National Natural Science Foundation of China,No.81072786,No.81473630 and No.81202665+2 种基金Longhua Medical Project,No.D-09High level Project of the University of Educational Commission of Shanghai,China,No.2008GSP19Shanghai Leading Academic Discipline Project,No.J50305
文摘AIM:To determine the molecular mechanisms of Shugan decoction(SGD) in the regulation of colonic motility and visceral hyperalgesia(VHL) in irritable bowel syndrome(IBS).METHODS:The chemical compounds contained in SGD were measured by high-performance liquid chromatography.A rat model of IBS was induced by chronic water avoidance stress(WAS).The number of fecal pellets was counted after WAS and the pain pressure threshold was measured by colorectal distension.Morphological changes in colonic mucosa were detected by hematoxylin-eosin staining.The contents of tumor necrosis factor(TNF)-αin colonic tissue and calcitonin-gene-related peptide(CGRP)in serum were measured by ELISA.The protein expression of serotonin[5-hydroxytryptamide(5-HT)],serotonin transporter(SERT),chromogranin A(Cg A)and CGRP incolon tissue was measured by immunohistochemistry.RESULTS:SGD inhibited colonic motility dysfunction and VHL in rats with IBS.Blockers of transient receptor potential(TRP)vanilloid 1(TRPV1)(Ruthenium Red)and TRP ankyrin-1(TRPA1)(HC-030031)and activator of protease-activated receptor(PAR)4 increased the pain pressure threshold,whereas activators of PAR2and TRPV4 decreased the pain pressure threshold in rats with IBS.The effect of SGD on pain pressure threshold in these rats was abolished by activators of TRPV1(capsaicin),TRPV4(RN1747),TRPA1(Polygodial)and PAR2(AC55541).In addition,CGRP levels in serum and colonic tissue were both increased in these rats.TNF-αlevel in colonic tissue was also significantly upregulated.However,the levels of 5-HT,SERT and Cg A in colonic tissue were decreased.All these pathological changes in rats with IBS were attenuated by SGD.CONCLUSION:SGD alleviated VHL and attenuated colon motility in IBS,partly by regulating TRPV1,TRPV4,TRPA1,PAR2,5-HT,Cg A and SERT,and reducing CGRP and TNF-αlevel.
基金Supported by National Natural Science Foundation of China,No.81072786the Innovation Program of the Shanghai Municipal Education Commission,No.12YZ065the Longhua Medical Project,No.D-09
文摘AIM:To evaluate the therapeutic effect of Shugan-decoction(SGD)on visceral hyperalgesia and colon gene expressions using a rat model.METHODS:Ninety-six adult male Wistar rats were randomized into six equal groups for assessment of SGD effects on psychological stress-induced changes using the classic water avoidance stress(WAS)test.Untreated model rats were exposed to chronic(1 h/d for 10 d consecutive)WAS conditions;experimental treatment model rats were administered with intragastric SGD at1 h before WAS on consecutive days 4-10(low-dose:0.1g/mL;mid-dose:0.2 g/mL;high-dose:0.4 g/mL);control treatment model rats were similarly administered with the irritable bowel syndrome drug,dicetel(0.0042g/mL);untreated normal control rats received no drug and were not subjected to the WAS test.At the end of the 10-d WAS testing period,a semi-quantitative measurement of visceral sensitivity was made by assessing the abdominal withdrawal reflex(AWR)to colorectal balloon-induced distension(at 5 mmHg increments)to determine the pain pressure threshold(PPT,evidenced by pain behavior).Subsequently,the animals were sacrificed and colonic tissues collected for assessment of changes in expressions of proteins related to visceral hypersensitivity(transient receptor potential vanilloid 1,TRPV1)and sustained visceral hyperalgesia(substance P,SP)by immunohistochemistry and real-time polymerase chain reaction.Inter-group differences were assessed by paired t test or repeated measures analysis of variance.RESULTS:The WAS test successfully induced visceral hypersensitivity,as evidenced by a significantly reduced AWR pressure in the untreated model group as compared to the untreated normal control group(190.4±3.48 mmHg vs 224.0±4.99 mmHg,P<0.001).SGD treatments at mid-dose and high-dose and the dicetel treatment significantly increased the WAS-reduced PPT(212.5±2.54,216.5±3.50 and 217.7±2.83 mmHg respectively,all P<0.001);however,the low-dose SGD treatment produced no significant effect on the WAS-reduced PPT(198.3±1.78 mmHg,P>0.05).These trends corresponded to the differential expressions observed for both TRPV1 protein(mid-dose:1.64±0.08 and high-dose:1.69±0.12 vs untreated model:3.65±0.32,P<0.001)and mRNA(0.44±0.16 and0.15±0.03 vs 1.39±0.15,P<0.001)and SP protein(0.99±0.20 and 1.03±0.23 vs 2.03±0.12,P<0.01)and mRNA(1.64±0.19 and 1.32±0.14 vs 2.60±0.33,P<0.05).These differential expressions of TRPV1 and SP related to mid-and high-dose SGD treatments were statistically similar to the changes induced by dicetel treatment.No signs of overt damage to the rat system were observed for any of the SGD dosages.CONCLUSION:Shugan-decoction can reduce chronic stress-induced visceral hypersensitivity in rats,and the regulatory mechanism may involve mediating the expressions of TRPV1 and SP in colon tissues.
基金supported by the National Natural Science Foundation of China(No.81360544)
文摘Objective:To investigate the effect of Chaihu Shugan decoction(CSD)on gastric smooth muscle cells(GSMCs)apoptosis in rats with functional dyspepsia(FD).Methods:48Sprague-Dawley(SD)rats were randomly assigned into six groups:a normal control group,a model group,apositive control(domperidone)group and low-,middle-and high-dose CSD groups.A rat model of FD was established by constantly squeezing their tails.The rats were administered CSD(0.16g/mL,0.32g/mL,0.64g/mL)or domperidone(0.3 g/L)via intragastric gavage for four weeks.The gastric emptying rate was detected at 4 weeks post-administration.Apoptosis of GSMCs was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and the mitochondrial morphology was observed by transmission electron microscopy.The expression of Bcl-2and Bax was measured by immunohistochemistry.Results:FD resulted in marked reduction of gastric emptying rate,severe gastric tissue damage and mitochondria injury,but were reversed by CSD treatment(P<0.05).The apoptosis-induced protein Bax was markedly down-regulated by CSD,whereas the expression of the anti-apoptotic Bcl-2 protein was notably increased(P<0.05).Furthermore,CSD could protect the FD rats against GSMCs apoptosis manifested by a decreased in TUNEL-positive cells(P<0.05).Conclusion:CSD could alleviate GSMCs apoptosis in FD rats,possibly by the modulation of Bcl-2 and Bax expression,and the suppression of mitochondria injury.
基金National Science Fund Subsidized Project(No.81774289)。
文摘Objective:To explore the molecular biological mechanism of Shugan Jianpi Decoction in treating depression-related breast cancer based on network pharmacology.Methods:The active compounds of Shugan Jianpi Decoction were explored to obtain their drug targets,and the venny network,"TCM-component-target"network,PPI network,"pathway-gene"network,GO and KEGG enrichment results were constructed using relevant softwares.Results:A total of 121 active ingredients,250 genes,2357 GO functions and 184 KEGG pathways were obtained.Conclusion:The active ingredients of Shugan Jianpi Decoction are quercetinll、kaempferol、luteolin、naringenin.The key targets are MAPK1,MAPK3,RELA,and AKT1.GO functions include cellular response to hormone stimulus、cellular response to lipid、cellular response to oxidative stress and so on.KEGG mainly involves PI3K-Akt,microRNAs,and FoxO signaling pathways.This study preliminarily explores the molecular biological mechanism of Shugan Jianpi Decoction in the treatment of depression-related breast cancer,and speculates that it mainly acts by arresting the cell cycle,inhibiting cancer cell proliferation,mediating cancer cell apoptosis,and preventing its recurrence and metastasis,which provides new evidence and new direction for subsequent clinical application and experimental research.
文摘Chronic calculous cholecystitis is a common clinical medical disease,which is classified as"hypochondriac pain"in traditional Chinese medicine(TCM).It is caused by liver failure and stagnation of liver qi.Therefore,the method of Soothing the liver and promoting bile flow is often used for regulating and harmonizing qi and blood.This paper discusses its mechanism of action,and points out that Shugan Lidan decoction has great effect on the treatment of chronic calculous cholecystitis,especially in the early treatment of the disease and delaying the progress of the disease,which provides help for the clinical treatment of chronic calculous cholecystitis.
