Study On Pharmacodynamics And Distribution Quantitative Composition Of Atractylodes Lancea Before And After Processing

Atratylodes lancea is from the dried rhizome of Atratylodes lancea?Thunb.?DC.and Atratylodes lancea?DC.?Koidz.?Compositae?.Rhizoma Atractylodis and Branfried Rhizoma Atractylodis are frequently used in prescriptions of TCM.The pungent and dryness of Rhizoma Atractylodis treating the dampness retention in the middle-jiao rats are strong in clinical.And yet,the pungent and dryness is alleviated and the effect of strengthening spleen is enhanced of Rhizoma Atractylodis after stir-baking with bran.But it is still unknown that the mechanism of the increase of the effect of strengthening spleen and the dryness alleviation after stir-baking with bran.This paper is part of the National Nature Science Foundation of China?No.81541080?project that a systematic research we have made.In this paper,we have a further study on three major qualitative constitutes-Diisobutyl phthalate,Atractyloside A-in Rhizoma Atractylodis processing.On the basis of qualitative constitute and pharmacodynamical changes of the Rhizoma Atractylodis and Branfried Rhizoma Atractylodis,we continue researching on the connection between qualitative and pharmacodynamical changes.And then,the scientific connotation of the processing mechanism of Rhizoma Atractylodis and Branfried Rhizoma Atractylodis would be better illustrated.We have a study on acute toxity of Diisobutyl phthalate using improved Karber's method.The result showed that the LD₅₀is 12153.5 mg/kg and the 95%confidence interval of LD₅₀ is10284.4¹4362.2mg/kg.According to grading toxicity compound standard through the mouth,Diisobutyl has low toxicity which indicates the connection between decresing content and reducing toxicity.Based on prelimilary study,we continue researching on effects of Atratctylodes A.The syndrome of spleen deficiency model was imitated by administration of Xiaochengqi decoction and semi-starvation in rats.Here,the gastrointestinal motility was evaluated by testing gastric emptying and intestinal propulsion,and histopathological changes by hematoxylin and eosin?HE?.In addition,ELISA and immunohistochemistry gastric tissues were employed to determine the concentration of motilin and gastrin in serum and the expression level of C-kit,proliferating cell nuclear antigen?PCNA?and epidermal growth factor receptor?EGFR?,respectively.The intestinal propulsion rate and gastric emptying rate was significantly lower in model group than that in control group?P<0.05?,suggesting that syndrome of spleen deficiency model leads to gastrointestinal motility disorder in model rats.The intestinal propulsion rate was significantly higher in Atratctylodes A groups and domperidone group than model group?P<0.05?,and the gastric emptying rate was also significantly higher than model group?P<0.05?.The results showed that the serum gastrin level and motilin level were significantly lower in model group than that in control group and significantly higher after treatment with Atratctylodes A and domperidone?P<0.05?.By HE staining,we observed that each dose of Atractyloside A can ameliorate pathological changes of gastric tissues in syndrome of spleen deficiency model rats,but have a little therapeutic benefit for jejunum even at high-dose.The area percent of C-kit of each Atractyloside A groups were also significantly?P<0.05?higher than those in syndrome of spleen deficiency model rats.Meanwhile,the area percent of PCNA and EGFR expression of each Atractyloside A groups is significantly?P<0.05?lower than those in syndrome of spleen deficiency model rats.Above all,Atractyloside A can protective and enhance motility on gastrointestinal system in rats with syndrome of spleen deficiency.On the basis of protective and enhanced motility effects of Atractyloside A,we have a further study on its excretion pharmacokinetic using HPLC-ELSD and UFLC-MS respectively.The result showed that Atratctylodes A s mainly excreted in the form of metabolites.Excretion percentages of feces and urine is31.60%and 0.34%respectively.And there was difference in the excretion percentages of feces between day 1 and day 2.It is indicated that Atratctylodes A is poorly absorbed and have low absolute bioavailability in rats.Meanwhile,the metabolic speed of Atratctylodes A is also very fast.Moreover,pharmacokinetic parameters of Atratctylodes A are:t_1/2/h=1.30,t_max/h=1,C_max/ng·mL^-1=59.13,AUC_0-t/ng·h/mL=147.23,AUC_0-?/ng·h/mL=149.88.It is indicated that Atratctylodes A was absorbed as the form of metabolites quickly trough digestive tract.The result could further verify our above results.Above all,the acute toxity of Diisobutyl phthalate in mice was studied.We have also determined the protective and enhance motility effects of Atratctylodes A on gastrointestinal system rats.What's more,we have a further study on Atratctylodes A excretion and pharmacokinetic in rats.Additionally,our study analyzes the scientific connotation of the processing mechanism of Rhizoma Atractylodis and Branfried Rhizoma Atractylodis more fully.