| Irritable bowel syndr-ome(IBS)is a recognized clinically high and difficult disease.The main symptoms are abdominal pain or abdominal discomfort,and diarrhea,constipation and other defecation symptoms.Visceral hypersensitivity is an important pathophysiological basis in the pathogenesis of irritable bowel syndrome.Sinisan compound prescription is a clinical prescription for the treatment of irritable bowel syndrome.This study explored the effects of Sinisan compound and its effective components on visceral hypersensitivity rat model and 5-HT signaling pathway.Research work is mainly divided into four parts:1?Using network pharmacology to predict the mechanism of action of Sinisan compound in treating visceral hypersensitivity rats.Through literature excavation,71 kinds of undetermined components were screened and 32 important target points were obtained after screening with the help of the TCMSP database.16 pathways were screened through the combination of DAVID 6.8 search and irritable bowel syndrome,which can be classified into neurotransmitters.With the three modules of hormonal regulation.inflammatory factor regulation,and intestinal microbial infection,of which neurotransmitters and hormonal regulation are the most important,combined with irritable bowel syndrome is now backlit,so hsa04726 is selected in this module:Serotonergic synapse and 5-Serotonin signaling pathway was studied.2?To study the effects of Sinisan compound and its active ingredient combinations on the general state of rats,intestinal sensation(abdominal withdraw al reflex,minimum capacity threshold).Compared with the model group,the appearance and behavior of the Sinisan compound group and paeoniflorin plus synephrine+glycyrrhizic acid were significantly improved,the coat color gradually became bright and smooth,most of the rats' constipation symptoms disappeared,and faeces were transferred.The appearance of grayish-brown granules.the eyelid condition was improved,the activity was more active,and the symptoms were significantly improved.Paeoniflorin+glycyrrhizic acid group also improved the appearance of rats,while paeoniflorin,synephrine.and glycyrrhizic acid monomer groups showed no obvious improvement in appearance.Synephrine group,Paeoniflorin+Glycyrrhizic acid group or Paeoniflorin+Synephrine+Glycyrrhizic acid group had a significant effect on the threshold value of rats(P<0.05),Sinisan.Paeoniflorin+Synephrine group The threshold value of the rat has a very significant regulation(P<0.01)and is close to the normal group,the degree of deviation is small.3?To study the effects of Sini Powder's effective components(paeoniflorin,glvcyrrhizic acid.and synephrine)on the general state of rats,intestinal sensation(abdominal withdrawal reflex,minimum volume threshold)and 5-HT signaling pathway.Significant protein levels of 5-HT signaling pathway in rat colon were measured by enzyme-linked immunosorbent assay(ELISA).5-HT3aR and TPH1 protein levels were detected by Western Blot,and rat colon was determined by realtime fluorescent quantification(qRT-PCR)5 The mRNA level of the important marker protein of the HT signaling pathway.The combination of active ingredients of Sini San can significantly reduce the content of 5-HT in the colon,protein levels of TPH1,5-HT3R,and mRNA levels(P<0.05.P<0.01),and significantly upregulate 5-HT4R in the colon of model rats.SERT protein levels and mRNA levels(P<0.05,P<0.01),and protein levels and mRNA levels have a synchronous trend.Using factorial analysis.it was found that paeoniflorin+glycyrrhizic acid group and paeoniflorin+ synephrine group had a synergistic effect,and its effect on the molecular level was better than the single effective component group.Paeoniflorin+glycyrrhizic acid+synephrine The effect of the combination of Sini Powder and Sini Powder was similar,suggesting that the effective components of Sini Powder have a synergistic effect in the regulation of 5-HT signaling pathway.According to the cluster analysis diagram combined with Sini Powder,we can intuitively see that there is no significant difference between the glycyrrhizic acid group and the model group,there is a certain difference between the synephrine group or paeoniflorin group and the model group.but the corrective effect is not obvious.and within the group big different.There is a significant difference between the active ingredient combination group and the model group,which has a significant corrective effect.Compared with the single component group,the points within the active ingredient combination group were more concentrated,and the location of the inhabited area obviously went to the normal group.Paeoniflorin+synephrine+glycyrrhizic acid combination is similar to Sinisan,and it has better multi-target rectification effect on 5-HT pathway,suggesting that paeoniflorin+synephrine+glycyrrhizic acid combination and Sinisan compound have large effect on model The abnormal state of 5-HT signaling pathway in mice has better multitarget correction.In summary,the Sinisan compound and its active ingredients have a significant improvement in the general state of the visceral hypersensitivity model rats and intestinal sensation;meanwhile,the protein levels of the 5-HT signaling pathway in visceral hypersensitivity model rats The level of mRNA has a significant regulatory effect;among them.paeoniflorin+synephrine+glycyrrhizic acid combination and Sini San compound have better multi-target rectification effect on the abnormal state of 5-HT signaling pathway in model rats.This study has theoretical significance for elucidating the mechanism of action of Sinisan compound and its active ingredient combination,and has guiding significance for the development of new drugs for irritable bowel syndrome. |
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