The Clinical Study Of Shengjiang Xiexin Decoction In Cold-Heat Complex Syndromes In The Treatment Of Ulcerative Colitis And The Mechanism Of 6-gingerol Intervention

ObjectiveUlcerative colitis is a chronic non-specific disease of the colon with abdominal pain,diarrhea,mucus,pus and blood in the stool as the main symptoms.At present,the cause of the disease is not very clear.There are many clinical choices of drugs,but there is a lack of drugs that are effective for ulcerative colitis and have few side effects.The treatment of ulcerative colitis by traditional Chinese medicine has received extensive attention and promotion due to its characteristics of syndrome differentiation and individualized treatment.The complex syndrome of Cold-Heat is a common syndrome of ulcerative colitis,and the clinical symptoms are more lingering and recurring.As one of the classic prescriptions for the treatment of cold and heat syndromes,Shengjiang Xiexin Decoction is widely used in chronic colitis,diarrheal irritable bowel syndrome,etc.,but there are few reports about its use in ulcerative colitis,and only a few trials Studies have shown that it has anti-inflammatory effects,and ginger,as a monarch drug,has been reported to have anti-inflammatory and anti-oxidant effects,but there are currently few in-depth studies on its anti-inflammatory mechanism.Therefore,this subject intends to conduct research from the following three aspects:1.Observe the application of Shengjiang Xiexin Decoction in clinical syndrome differentiation and treatment of UC(Cold-Heat complex syndrome),and evaluate its efficacy and clinical safety.2.Analyze the inflammatory response of 6-gingerol,the active ingredient of ginger in the Shengjiang Xiexin Decoction,on the inflammatory response of mice with ulcerative colitis caused by DSS and its effect on Th17/Treg balance.3.To explore the regulatory effect of 6-gingerol on the NF-κB signaling pathway,and to clarify the mechanism of 6-gingerol for improving intestinal inflammation.MethodsIn the first part of the clinical study,we adopted a randomized controlled method to treat patients with mild to moderate ulcerative colitis on the basis of mesalazine controlled treatment with Shengjiang Xiexin Decoction Observe the changes in clinical efficacy,TCM syndrome score,modified Mayo score,endoscopic score,and blood ESR,CRP content of the two groups of patients,and evaluate the clinical efficacy.In the second and third part of the experimental study,the test mice were divided into six groups.The levels of IL-6,IL-17 and IL-10 in serum and intestinal tissue were detected by ELISA;and The mRNA expressions of IL-6,IL-17,IL-10,RORyt and Foxp3 in intestinal tissues were detected by RT-PCR,RORyT;Flow cytometry to detect the expression of Th17/Treg,Westen blot to detect the protein expression of RORyT,FOXP3,p-IκBα and p-p65;HE staining was used to observe the inflammation of intestinal diseased tissues in each group and immunohistochemistry to detect the expression of IL-17,IL-10,p-IκBα and p-p65 in the intestinal tissues.ResultsThe first part of the clinical research results showed that the treatment group had 30 cases with a total effective rate of 93.3%;the control group had 26 cases with a total effective rate of 80.7%.Both the markedly effective and effective patients in the two groups can improve the symptoms after treatment,but the markedly effective and effective cases in the treatment group are significantly more than the control group,and the difference is statistically significant.Compared with the control group,the improvement of TCM syndrome score,the reduction of modified Mayo score,Endoscopic scoring and the down-regulation of ESR content in the treatment group were statistically significant compared with the control group.The second part of the experimental research results found that 6-gingerol can significantly reduce the levels of IL-6 and IL-17 in serum and intestinal tissues,and are significantly lower than the levels of UC mice.6-gingerol can increase the level of IL-10 in serum and intestinal tissues,and it is significantly higher than that in UC mice.In terms of both protein expression and mRNA level of intestinal tissue,6-gingerol can significantly inhibit the up-regulation of Th17 transcription factor RORyT induced by DSS and the down-regulation of Treg transcription factor FOXP3 induced by DSS.The third part of the experimental research results found that DSS increased the phosphorylation levels of IKBa and p65,while 6-gingerol treatment could significantly inhibit the levels of p-IKBa and p-p65 induced by DSS;After DSS treatment,p-p65 staining was mainly in the nucleus,with some staining in the cytoplasm,while 6-gingerol treatment could significantly reduce the density of p-p65 in the cytoplasm and nucleus.ConclusionThe clinical trial results showed that the Shengjiang Xiexin Decoction has a good clinical effect in the treatment of patients with Cold-Heat complex syndromes in traditional Chinese medicine in UC.In the end,clinical application is feasible,and its curative effect is no less than that of mesalazine monotherapy,with low adverse reactions and good results,especially in the improvement of patients’ clinical symptoms.Experimental results showed that 6-gingerol can inhibit the expression and secretion of IL-6,maintain the balance of Th17/Treg,thereby inhibiting Th17-mediated inflammation,and 6-gingerol can reduce DSS-induced inflammatory damage in UC mice by regulating the NF-κB signaling pathway.