Pharmacological Research Of Wei Chang An Pill And A New View On Its Antidiarrhea Efficiency

Objective:Diarrhea is one of common clinical symptoms of gastrointestinal dysfunction. The incidence of diarrhea is very high.The latest statistics show the incidence of diarrhea of whole population is 0.17-0.7 times per person per year in China, and it is 2.50-3.38 times per person per year in the children under 5 years old. At present, the treatment of nonspecific diarrhea is still a clinical issue needs to be studied. Wei Chang An pills can treat diarrhea effectively. In TCM it can aromatic herbs resolving turbidity, regulating qi to alleviate pain, strengthening stomach to relieve stagnation. In clinic it is used to treat diarrhea, fullness and pain of stomach and abdomen, indigestion and infantile dyspepsia. But this prescription includes poisonous Semen Crotonis Pulveratum, which restrict the clinical using of Wei Chang An pills. So removing Semen Crotonis Pulveratum from Wei Chang An pills or finding a substitute of Semen Crotonis Pulveratum had be a item of Tianjin Science and Technology Innovation funds. This study advanced a hypothesis that Natrii Sulfas could be the substitute of Semen Crotonis Pulveratum in Wei Chang An pills. The purpose of this research is to compare Semen Crotonis Pulveratum with Natrii Sulfas on intestinal movement, intestinal absorption and secretion, in order to elucidate the pharmacological effect and mechanism of all experimental drugs on diarrhea model. This study will find the necessary evidence to probe into the substitute of Semen Crotonis Pulveratum in Wei Chang An pills.Methods:1. Diarrhea rats model is established by administrating Folium Cassiae.2. Groups with different concentrations of BDS,YMF,BDS+DH and YMF+DH were established. Through testing the ileum liquid water metabolism of rabbit compared BDS with YMF and BDS+DH with YMF+DH on pharmacodynamic effects, in order to find the doses of Natrii Sulfas to substitute Semen Crotonis Pulveratum.3. Based on the results of test 2, through testing the rate of loose stools, colon movement and colon absorption compared BDS with YMF and BDS+DH with YMF+DH and WCA with TDF. we try to explore the evidence to probe into the substitute of Semen Crotonis Pulveratum in Wei Chang An pills.4. Based on the results of test 3, through testing the activity of Na+-K+-ATPase in the colonic epithelial cell and the serum electrolyte compared BDS with YMF and BDS+DH with YMF+DH and WCA with TDF. we tried to compare Natrii Sulfas with Semen Crotonis Pulveratum on the mechanisms of regulating the colon absorption.5. Based on the results of test 3, we tested the level of SP and VIP to compare BDS with YMF and BDS+DH with YMF+DH and WCA with TDF.Results:1. Diarrhea rats resulted by 5g/kg FXY showed the rate of loose stools reached 85.54%, the serum D-xylose content and the activity of Na+-K+-ATPase in the colonic epithelial cell decreased(P<0.01).2. Test dose of YMF and BDS had the same effects on the ileum liquid water metabolism(P>0.05).1.11 mg/ml and 2.22 mg/ml of YMF and BDS could accelerate the ileum liquid water absorption(P<0.01).22.2 mg/ml of BDS and 1g/ml of YMF can result the ileum liquid water increase(P<0.01). When the YMF and BDS combined with DH, the effect was same as the single-drug.3.33 mg/ml and 4.44 mg/ml combination with DH could accelerate the ileum liquid water absorption(P<0.01, P<0.05).3. The BDS can reduce the rate of loose stools and improve the colonic absorption(P<0.05), there was no difference in the same concentration YMF(P>0.05). When the YMF and BDS combined with DH, the action was same as the single-drug(P>0.05) and there were no different between YMF+DH and BDS+DH(P>0.05). But the effect of two combinations was different in the formula. The WCA could reduce the rate of loose stools and improve the colonic absorption(P<0.05), the TDF had not these action(P>0.05).4. BDS, BDS+DH and WCA could slower colon movement(P<0.05). YMF and YMF+DH had not effect on colon movement(P>0.05), but the TDF could slower colon movement(P<0.05).5. BDS could improve serum Na+, K+, Cl- (P<0.01, P<0.05, P<0.05) and the activity of Na+-K+-ATPase in the colonic epithelial cell (P<0.05).YMF could increase serum Na+, Cl- (P<0.01, P<0.05). BDS+DH could improve serum Na+, K+, Cl- (P<0.01, P<0.05, P<0.05) and the activity of Na+-K+-ATPase in the colonic epithelial cell (P<0.05).YMF+DH had the same action as BDS+DH(P>0.05).6. WCA could improve serum Na+, K+, Cl- (P<0.01, P<0.05, P<0.05)and the activity of Na+-K+-ATPase in the colonic epithelial cell (P<0.05).The function of adjusting serum Na+was better than BDS+DH(P<0.05). The function of adjusting the activity of Na+-K+-ATPase was better than BDS(P<0.05).TDF just can improve serum Na+(P<0.01).7. Lower concentration of BDS and BDS+DH debase the level of SP and VIP(P<0.01). Middle concentration of BDS just debase the level of VIP(P<0.01).YMF and YMF+DH had no effect on the level of SP and VIP(P>0.05).Both of the WCA and TDF could debase the level of SP and VIP(P<0.01).Conclusions:1. All of the BDS, BDS+DH, and WCA are able to improve the colon absorption, promote colonic water and electrolyte metabolism, adjust of the colon movement, and reduce the colon secretion. Low-dose of YMF improve intestinal water and electrolyte absorption,witch is similar to BDS. But the mechanism of YMF is not same as the BDS. Combined with DH, the acting target of two complex tends to similar. However, the action of YMF+DH is antagonized by WCA. BDS of WCA can not be substituted by YMF.2. Low dose BDS and BDS+DH can treat diarrhea.3. Through activating spleen and resolving dampness, harmonizing functional activities of qi,the WCA can stop the diarrhea. The therapeutic principles of WCA belong to treating diarrhea with regulating functions of zang and fu organs.