Jatamansi Iridoid Explore The Therapeutic Effects And Mechanisms Of Irritable Bowel Syndrome

Irritable bowel syndrome is one of the disorders of gastrointestinal function,with the characteristic of abdominal pain or discomfort,associated with characters change and habit change in stool.Epidemiological survey shows that the rate of this disease is as high as 10%to 20%in healthy people,accounting for more than 50%of the number of patients coming to the digestion department.Its basis of pathophysiology is mainly based on the abnormal of gastrointestinal kinetics and the increased visceral sensitivity,but the specific mechanism is not clear.The Chinese medicine attributed the irritable bowel syndrome to the scope of "intestinal depression",that the pathogenesis are most the liver depression and spleen deficiency and uncoordination of qi and blood,the main treatment is relieving the depressed liver and invigorating spleen to resolve dampness.Valeriana jatamansi Jones is commonly used herb of miao that can regulate Qi to relieve pain,diminish inflammation to stop diarrhea,dispel wind and dliminate dampness. It can be used in treating stomach and abdominal distension and pain,dyspepsia,diarrhea, dysentery,rheumatism and weakness in lumbar and knee,and so on.Modern research found that valeriana jatamansi Jones have a good therapeutic effect on diseases of the gastrointestinal.Preliminary studies confirmed that through the valeriana jatamansi Jones used in the treatment of IBS has a significant effect,and its technical Powder can improve the gastrointestinal function and the abnormal of nerve and spiritual activity of rat model induced by chronic stress.After the selection of its major components,iridoids plays the most important rold in the gastrointestinal motility hypersplenism and the abnormal of nerve and spiritual activity of the mice,so we can sure the effective part is the Iridoids components.Based on this,We designed a series of experiments to study the treatment and its mechanism of Iridoids composition of Valeriana jatamansi Jones of the IBS animal model.1 Research on Iridoids composition of Valeriana jatamansi Jones in the role of gastrointestinal function.1.1 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of normal miceMethods:Compared with normal group and YJBH group,mice which has given Iridoids composition of Valeriana jatamansi Jones as 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg was detected gastric emptying and small intestinal propulsion after 4 days drug given.Results:Compared with normal group,gastric emptying and small intestinal propulsion in 35.6mg/kg and 17.8mg/kg group was inhibited.It shows that Iridoids composition of Valeriana jatamansi Jones have inhibit function on gastrointestinal function of normal mice.1.2 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of mice with reserpineMethods:Compared with normal group,model group and YJBH group,mice with reserpine which has given Iridoids composition of Valeriana jatamansi Jones as 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg was detected gastric emptying and small intestinal propulsion after 6 days drug given.Results:Compared with model group,gastric emptying of 71.2mg/kg group was inhibited,and small intestinal propulsion has no significant change.Gastric emptying and small intestinal propulsion of 35.6mg/kg group were both inhibited.Small intestinal propulsion of 17.8mg/kg group was inhibited.It shows that Iridoids composition of Valeriana jatamansi Jones have inhibit function on gastrointestinal function of mice with reserpine.1.3 Effection of Iridoids composition of Valeriana jatamansi Jones on gastrointestinal function of IBS rats induced by chronic stressMethods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected AWR and stool quantity in 2 hours.Results:Compared with model group,pain threshold pressure and Maximum pressure threshold of three Iridoids composition of Valeriana jatamansi Jones groups were all improve,especially the 24.92mg/kg and 12.46mg/kg group(P＜0.001).Stool quantity of 24.92mg/kg and 12.46mg/kg group reduced obviously(P＜0.05).It shows that Iridoids composition of Valeriana jatamansi Jones can reduce the visceral sensitivity and the stool quantity of IBS rat model induced by chronic stress.2 Research on the Iridoids composition of Valeriana jatamansi Jones in the role of spiritual activity function2.1 Effection of Iridoids composition of Valeriana jatamansi Jones on spiritual activity function of IBS rats induced by chronic stressAnimals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detect the openfield test score and Sugar water choosed degree.Compared with model group,the horizontal and vertical motion score of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of lowering,but have no statistically significance.Sugar water choosed degree have no significant change. It means that Iridoids composition of Valeriana jatamansi Jones has central inhibitory action.2.2 Effection of Iridoids composition of Valeriana jatamansi Jones on weight and food intake of IBS rats induced by chronic stressAnimals were randomly divided into 7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the weight and food intake in 24 hours.Compared with model group,the rat weight of three Iridoids composition of Valeriana jatamansi Jones groups have no significant change,the food intake of them have a trend of increase,but have no statistically significance.It shows that Iridoids composition of Valeriana jatamansi Jones can improve food intake of IBS rats.2.3 Effection of Iridoids composition of Valeriana jatamansi Jones on abdominal pain of mice induced by acetic acidAnimals were randomly divided into normal group,Aspirin group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 71.2mg/kg,35.6mg/kg,17.8mg/kg,8.9mg/kg.0.6%acetic acid was injected into Peritoneal after 6 days drug given.Then we detected Latency of body torsion,0-10min times of body torsion,10-20min times of body torsion and 20min times of body torsion.Compared with model group,Latency of body torsion of 4 ridoids composition of Valeriana jatamansi Jones groups have no significant change.0-10min times of body torsion,10-20min times of body torsion and 20min times of body torsion were all obviously increase.It shows that ridoids composition of Valeriana jatamansi Jones can induce abdominal pain caused by acetic acid obviously. 3 Research on the Iridoids composition of Valeriana jatamansi Jones in the role of mechanism of action of rat model induced by chronic stress3.1 Effection of Iridoids composition of Valeriana jatamansi Jones on 5-HT and 5-HIAA in colon,serum and central of IBS rats induced by chronic stressMethods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the quantity of 5-HT and 5-HIAA in colon,serum and hippocampus by high-pressure liquid method, detected the quantity of 5-HT in amygdale and hypothalamus by immunohistochemistry method.Then we used imag-pro plus analysis software to do Semi-quantitative analysis on area and IOD of Immunostaining positive cells.Results:Compared with model group,the content of 5-HT and 5-HT/5-HIAA(P＜0.05) in serum of 24.92mg/kg,12.46mg/kg group were ruduced,but the conent of 5-HIAA have no significant change.Three Iridoids composition of Valeriana jatamansi Jones groups can induce the 5-HT content in colon obviously(P＜0.05),and the 24.92mg/kg and 6.23mg/kg group can reduce 5-HT/5-HIAA obviously(P＜0.05),24.92mg/kg group can also reduce 5-HIAA in colon(P＜0.05).24.92mg/kg group can reduce 5-HT/5-HIAA in hippocampus(P＜0.05).Three Iridoids composition of Valeriana jatamansi Jones groups can reduce 5-HT in amygdale and hypothalamus,especially the 12.46mg/kg group(P＜0.01).It shows that Iridoids composition of Valeriana jatamansi Jones can reduce 5-HT content in colon,serum,amygdale and hypothalamus of IBS rat induced by chronic stress.3.2 Effection of Iridoids composition of Valeriana jatamansi Jones on 5-HT3R mRNA expression of IBS rats induced by chronic stressMethods:Animals were randomly divided into 6 groups:normal group,model group, OSD group,FXT group,MSP group and Iridoids composition of Valeriana jatamansi Jones groups.Model replicating method is chronic stress for 28 days.At the same time, drug were given.Then we detected the 5-HT3R mRNA expression by RT-PCR.Results:Compared with model group,5-HT3R mRNA expression of Iridoids composition of Valeriana jatamansi Jones group inhibited.It means that it can inhibite the 5-HT3A receptor expression in IBS rat model.It is speculated that this components feedback adjusting the this receptor's expression through receptor-binding with 5-HT3A receptor.3.3 Effection of Iridoids composition of Valeriana jatamansi Jones on THP1 mRNA expression of IBS rats induced by chronic stressMethods:Animals were randomly divided into 6 groups:normal group,model group, OSD group,FXT group,MSP group and Iridoids composition of Valeriana jatamansi Jones groups.Model replicating method is chronic stress for 28 days.At the same time, drug were given.Then we detected the THP1 mRNA expression by RT-PCR.Results:Compared with model group,all groups have no significant change.It may means that Iridoids composition of Valeriana jatamansi Jones doesn't regulate the TPH1 transcription expression.3.4 Effection of Iridoids composition of Valeriana jatamansi Jones on SP and VIP of IBS rats induced by chronic stressMethods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then we detected the content of SP and VIP in plasma and colon.Results:Compared with model group,the content of SP and VIP in plasma of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of reduce, especially the 24.92mg/kg group(P＜0.05).The VIP content in colon of these three groups have a trend of reduce,especially the 12.46mg/kg and 6.23mg/kg group(P＜0.05).It shows that Iridoids composition of Valeriana jatamansi Jones can may improve the IBS symptoms by regulating the SP and VIP content.3.5 Effection of Iridoids composition of Valeriana jatamansi Jones on mast cell of IBS rats induced by chronic stressMethods:Animals were randomly divided into7 groups:normal group,model group, OSD group,FXT group and Iridoids composition of Valeriana jatamansi Jones groups in quantiy of 24.92mg/kg,12.46mg/kg,6.23mg/kg.Model replicating method is chronic stress for 28 days.At the same time,drug were given.Then take the colon 3cm away from the anus,using toluidine blue staining method,and count the number of mast cells by low magnification microscope.Results:Compared with model group,the mast cell number of three Iridoids composition of Valeriana jatamansi Jones groups have a trend of reduce,but the result have no statistically significance.It means Iridoids composition of Valeriana jatamansi Jones may reduce the mast cell number in colon.Above all,Iridoids composition of Valeriana jatamansi Jones have a significant effect on improving the symptoms of IBS rat model induced by chronic stress,the mechanism may be involved from the colon to the central,including the totally regulated role of 5-HT system,gastrointestinal hormones system and the mast cells immune system.Our research fixed that Iridoids composition of Valeriana jatamansi Jones was the active ingredient in Valeriana jatamansi Jones treating IBS for the first time.And in-depth investigate its mechanism from neurotransmitter,gastrointestinal hormone and mast cell immune system.Our reaserch lay a solid of theoretical and experimental foundation in exploring our characteristical national new drugs.And it provides the basis of pharmacodynamics for improving clinical standard of 77 version Pharmacopoeia...