Comparative study on efficacy for Hedysari Radix before and after honey-processing paired with vinegar-processed Curcumae Rhizoma against colitis-associated colorectal cancer
Objective:To study on efficacy and immunomodulatory mechanism for Hedysari Radix(HR)before and after honey-processing(HPHR)paired with vinegar-processed Curcumae Rhizoma(VPCR)against colitis-associated colorectal cancer(CAC).Methods:Seventy-five SPF-grade C57/6J mice were randomly divided into five groups:control group,Azoxymethane(AOM)/Dextran sulphate sodium salt(DSS)group,Sulfasalazine group,HR∶VPCR(4∶1)group(6.825 g/kg),and HPHR∶VPCR(4∶1)group(6.825 g/kg).While the CAC mouse model was induced by the combination of AOM and DSS.Each dosing group was given drug intervention and the control group was given saline,and the experiment was ended after 17 weeks of intervention.Body mass,DAI score,colon length,tumor counts,survival index,colon length/colon mass,colon and organ indices such as spleen,thymus,liver,lungs,kidneys and heart were calculated,and colonic lesions were observed by HE staining.The expression levels of interleukin(IL)-1 β and tumor necrosis factor(TNF)-α in serum were detected by ELISA.The expression of the immune cells was screened and predicted by reference transcriptome sequencing combined with immune infiltration analysis.The screened immune cells were detected by flow cytometry.Results:Compared with AOM/DSS group,both HR-VPCR and HPHR-VPCR significantly increased the body mass,colon length,survival rate and thymus index(P＜0.05,P＜0.01),and significantly decreased the DAI scores,tumor counts,HE pathology scores,colon length/colon mass,and indexes of organs such as the colon,spleen,thymus,liver,and lungs in association with the serum IL-1 β and TNF-α expression levels(P＜0.05,P＜0.01).However,the effect of HPHR-VPCR was significantly superior to HR-VPCR in terms of HE pathological scores in colon and TNF-α levels in serum(P＜0.05,P＜0.01).The transcriptome sequencing combined with immune infiltration analysis revealed that both HR-VPCR and HPHR-VPCR could reduce the CD4+T/CD8+T values and up-regulated the expression of CD4+T cells,CD8+T cells,and CD19+B cells in spleen.However,for the effect on the expression of CD8+T cells in spleen,the effect of HPHR-VPCR was significantly better than that of HR-VPCR(P＜0.01).Conclusion:Both HR-VPCR and HPHR-VPCR have the effect of treating CAC,and the mechanism is related to regulating the expression of T and B lymphocytes,regulating the immunity of the body,thus improving the inflammation,blocking the process of inflammation,and improving the colonic lesions.However,the mechanism by which HPHR-VPCR was superior to that of HPHR-VPCR in treating CAC was mainly related to lowering the levels of CD8+T cells and TNF-a,which in turn improved the pathological damage of inflammation in the colon.
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