The Jatamansi Treatment Of Irritable Bowel Syndrome, The Role And Mechanism

Irritable bowel syndrome (IBS) is a commen disease in clinical.The pathology of IBS is still not clear for lacking of the evidence of biochemical change and structural change. IBS is characteristed by altered gastrointestinal motility, altered visceral sensation and neuropsychic change.The recent research shows that there are abnormal 5-HT content , abnormal gut hormone level (such asVIP,SP) and changed immune state in IBS patients,which may relate with onset of IBS.The investigation shows that 50%-100% of IBS patients have psychological problems,which indicates CNS may takes account for the pathogenesis of IBS.The relation may be as below:①The emotion facters such as depression ,anxiety and tension may induce dysfunction of gastrointestinal molity and secretion by brain-gut axis and intensify the symptom of IBS.②IBS may have the same pathogenesy with affective disorder. On the one hand, the abnormal anabolic metabolism of neurotransmitter such as 5-HT which existed in the CNS may induce affective disorder.On the other hand,5-HT,as one of brain-gut peptides, plays an important role in the gastrointestinal motility,visceral sensation conduction,absorption and secretion function of intestinal tract.Increaing 5-HT concentration in the periphery plays an important role in the onset of IBS.In a word,IBS is a physiological and psychological diseases accompanied with abnormal neuropsychic function and altered gastrointestinal function.Chinese medicine contribute the pathogenesis of IBS to stagnation of liver-QI with deficiency of the spleen.Disturbence emotion,anger and depression, excessive anxietas can lead to depression of liver-QI and dys-splenism. Treatment principle is to Soothe flow of liver qi and recuperating Qi.Zhizhuxiang is a traditional medicinal herb used by many races in southwest of china.It can regulate Qi and the middle warmer, eliminate cold and dampness ,activate blood and make detumescence. Zhizhuxiang is used principally to cure the disease such as dyspepsia,diarrhea,dysentery,rheumatic arthralgia,waist and knee lassitude, abdominal swelling and pain, the children's in Digestion.The research indicates that Zhizhuxiang has the pharmacological action like inhibitory action of the gastrointestinal motility, sedation, analgesia and anticonvulsant action.It is presumed that Zhizhuxiang may improve the clinical symptome of IBS according to the recognition of indication of Zhizhuxiang in civilian usage , the modern pharmacological research and clinical application.The aim of this subject is to establish a model of irritable bowel syndrome in rats by exposing to chronic unpredictable strssors and feeding alone and to screen pharmacological active site of Zhizhuxiang.Then, to investigate the effect of Zhizhuxiang on gastrointesetinal function and neuropsychic fuction in the basis of establishing a model of irritable bowel syndrome in rats by exposing to chronic unpredictable strssors.And to explore the mechanism of Zhizhuxiang in those aspects:anabolic metabolism of 5-HT in brain and gut,the concentration change of gut hormones(for instanceVIP,SP) and immunization facter(for instance MC).The results of this subject can provide experimental support for the therapy of Zhizhuxiang on IBS and make development in the recognition of Chinese herb which can Soothe flow of liver qi.1 Establishment of a model of irritable bowel syndrome in rats by exposing to chronic unpredictable strssorsMethod:160-180g SD male rats were dividied into two groups at random:control group and model group.The animals of control group were housed 7-8 in a cage without any stimulation.The animals of model group were singly housed and were exposed to chronic unpredictable strssors for four weeks. Assessed visceral sensation by abdominal withdrawl reflex (AWR) valve pressure and assessed gastrointestinal motility by counting the feces granules. By open-field test and fluid consumption test to evaluate the neuropsychic fuction of animals. Measured the change of body weight and food intake.Result: 7 days afer making model,the faces granules of Model group were significantly higher in model group than in control group(P<0.05).10 days afer making model,The AWR value pressure were significantly lower (P<0.05).20 days after making moder,the model group showed reduced squares crossing and rearing in open-field test and a significant reduced preference for sucrose solutions as compared with control group(P<0.05).The body weight of model group animals decreased significantly(P<0.05).There was no difference between control group and model group in foof intake.Conclusion:By exposing to chronic unpredictable strssors,the animal display some change:the excited gastrointestinal motility,the viscera hypersensitivity and the change of the neuropsychic fuction.Those changes imitate the main symptom of IBS.The model of irritable bowel syndrome in rats by exposing to chronic unpredictable strssors is effective and successful and can apply for the durg research.2 The therapeutic effect and the mechanism reseach of zhizhuxiang on IBS2.1Screening the pharmacological active site of Zhizhuxiang2.1.1 Screening the pharmacological active site of Zhizhuxiang on the gastrointestinal motilityMethod: Animal models were induced by intraperitoneal injection of reserpine everyday.6 days after administration and making model ,measured gastric emptying rates and small intestine propulsion rates. Result: essential oil, valtrate ,baldrinal and Zhizhuxiang fine powder had inhibitory activity on gastrointestinal motility(P<0.05).Zhizhuxiang fine powder and essential oil had the better effect among them.2.1.2 Screening the pharmacological active site of Zhizhuxiang on the neuropsychic fuctionMethod:Investigated the effect of zhizhuxiang extract(essential oil, valtrate ,baldrinal),Zhizhuxiang fine powder and Zhizhuxiang water decoction on autonomic activities in normal mice and in the mice models which induced by intraperitoneal injection of reserpine after administration for 3 days. Investigated the effect of zhizhuxiang extract (essential oil, valtrate ,baldrinal),Zhizhuxiang fine powder and Zhizhuxiang water decoction on fast time in tail suspension test. Result: Essential oil, valtrate , baldrinal and Zhizhuxiang water decoction had pharmacological activity on neuropsychic fuction.Zhizhuxiang water decoction, valtrate and baldrinal had the higher activity.Conclusion:The effect of zhizhuxiang on gastrointestinal function and neuropsychic function may be the result from synergistic effect among all active sites of Zhizhuxiang.2.2 The pharmacological effect of zhizhuxiang in the rat model of irritable bowel syndrome by exposing to chronic unpredictable strssorsMethod: SD male rats were dividied into 7 groups:control group,model group,high dose of zhizhuxiang find powder group,middle dose of zhizhuxiang find powder group,low dose of zhizhuxiang find powder group,tegaserod group, fluoxetine group.Control group were housed 7-8 in a cage without any stimulation. The animals of the other groups were singly housed and were exposed to chronic unpredictable strssors for 24days. Assessed visceral sensation by abdominal withdrawl reflex (AWR) valve pressure and to assess gastrointestinal motility by counting the feces granules. By open-field test and fluid consumption test to access the neuropsychic fuction of animals. Measured the change of body weight and food intake of all groups animals.Result:All dose of zhizhuxiang fine powder improved the abnormal visceral sensation and abnormal defecation(P<0.05)and increased preference for sucrose solutions(P<0.05).Zhizhuxiang also increased behavior scores of open-field test.But the activity was not significant(P>0.05).Zhizhuxiang fine powder had no effect on body weight and food intake (P>0.05). Conclusion:Zhizhuxiang fine powder can improve the abnormal gastrointestinal function and the abnormal neuropsychic function.,which show that zhizhuxiang have therapeutic effect on IBS.2.3 The therapeutic mechanism research of zhizhuxiang in the rat model of irritable bowel syndrome by exposing to chronic unpredictable strssorsMethod:SD male rats were dividied into 7 groups at random:control group,model group,high dose of zhizhuxiang find powder gourp, middle dose of zhizhuxiang find powder gourp,lowe dose of zhizhuxiang find powder gourp, tegaserod group,fluoxetine group.Control group were housed 7-8 in a cage without any stimulation.The animals of the other groups were singly housed and were exposed to chronic unpredictable strssors.After making model and administration for 24 days,executed the animals. Measured the 5-HT and 5-HIAA concentration in the serum,colon and hypothalamus by HPLC-ECD.Measured 5-HT content in the hippocampus and amygdaloid nucleus by immunochemistry. Measured the VIP and SP concentration in the plasma and colon by radioimmunoassay. Measured MC amount in the colon by applying toluidine blue stainsReasult:The concentration of 5-HT in the serum,colon,hypothalamus, hippocampus and amygdaloid nucleus of the model animal increased significantly.But the concentration of 5-HIAA had no change.The level of VIP and SP in plasma of the model animal got low and the level of SP in the colon got high significangtly.The amount of MC in the colon of the model animal had the increasing trend,but no statistical differenceZhizhuxiang fine powder decreased 5-HT concentration in the colon, hypothalamus,hippocampus and amygdaloid nucleus.Zhizhuxiang fine powder decreased the SP concentration in the colon .The 0.7g/kg zhizhuxiang fine powder increased the VIP concentration in the colon.All dose of zhizhuxiang fine powder had the decreased tendency of MC amount,but no statistical difference.Conclusion:The symptom of IBS model animal may be induced by abnormal 5-HT content and abnormal gut hormone level and increased MC amount .The effect of zhizhuxiang improving the symptome of IBS may be the result from decreasing 5-HT content in the CNS and peripheral tissues,changing the gut hormone SP and VIP concentration.and adjusting immune state.In summary:The rat model established by exposing to chronic unpredictable strssors is effective and successful as a IBS animal model and can apply for the durg research.The effect of zhizhuxiang on gastrointestinal function and neuropsychic function may be the result from synergistic effect among all active sites of Zhizhuxiang.Zhizhuxiang fine powder can improve the abnormal gastrointestinal function and the abnormal neuropsychic function in the IBS rat model,which may be the result from changing the gut hormone SP and VIP concentration and decreasing 5-HT content in the CNS and peripheral tissues.