The Study On The Mechanism Of Action Of Polysaccharides From Aconitum Brachypodum-XP-10 In Anti-tumor Immunological Therapy

Compromised immune system is tightly linked with initiation and progression of tumor.Conversely,it is an important strategy to control tumor progression by enhancing immune function.There are many polysaccharide with significantly immunomodulatory activity in natural world,these polysaccharides usually were widely applied to anti-tumor immunological therapy and against side effect of chemotherapy drugs.However,The price of these drug is so expense that many tumor patients can not pay for it.Therefore,it is of great significance and value to search for high efficiency and low price polysaccharides with anti-tumor immune activity from traditional Chinese medicine.Aconitum brachypodum,an ethnic medicine in yunnan,is a plant of aconite with a wide range of pharmacological effects,and aconite alkaloids are its main active components.However,the utilization rate of polysaccharides is low and there are few reports on polysaccharide composition.The research group previously found that XP-10,a component of polysaccharides from Aconitum brachypodum has significant immunomodulative activity,and the research results have applied for a patent for invention(Extraction method and application of polysaccharide from Aconitum brachypodum,patent no: CN107936130 B).This paper mainly studies the anti-tumor immunological effect of XP-10 in vitro and in vivo,and provides scientific basis for the further development of polysaccharides.Therefore,it is of great significance and value to search for highefficiency and low price polysaccharides with anti-tumor immune activity from traditional Chinese medicine.Aconitum brachypodum,an ethnic medicine in yunnan,is a plant of aconite with a wide range of pharmacological effects,and aconite alkaloids are its main active components.However,the utilization rate of polysaccharides is low and there are few reports on polysaccharidecomposition.The research group previously found that XP-10,a component of polysaccharides from Aconitum brachypodum has significant immunomodulative activity,and the research results have applied for a patent for invention(Extraction method and application of polysaccharide from Aconitum brachypodum,patent no:CN107936130 B).This paper mainly studies the anti-tumor immunological effect of XP-10 in vitro and in vivo,and provides scientific basis for the further development of polysaccharides.Firstly,the immunodulative activity of A were examined and analysed based on the lymphocyte proliferation assay.Results showed that XP-10 treatment markedly promoted Con A-induced T cell proliferation and LPS-induced B cell proliferation.Additional,XP-10 as motigen also could enhanced lymphocyte proliferation and cytokines secretion(IFN-??IL-2 and IL-6)in XP-10 induced lymphocyte proliferation assay.Nevertheless,XP-10 have no influence on DC cells,included surface marker expression(CD86,CD80 and CD11c)and IL-12 production.These results in this section indicated that XP-10 exerted significantly immunomodulating activity in vitro.Subsequently,immunoregulatory function of XP-10 in CTX induced immunosuppressive models was investigated.Results demonstrated that administration of XP-10(125mg/kg,p.o)could against the reduction of organ index and weight,promote the recovery of spleen T cell proliferation,down-regulated the proportion of Treg(CD4+Foxp3+T cells).However,XP-10 did not affect the percent of B220+B cells,Th17(CD4+IL-17+),CD4+T cells,CD8+T cells and the ratio of CD4+/CD8+,meanwhile,have on impact on blood routine in CTX induced immunosuppressive models.These results in this section demonstrated that XP-10 could enhance the immune function in immunosuppressive mice.Finally,we further investigated the therapeutic potential of XP-10 on Experimental Murine H22 Metastasis Models and explored the underlying mechanism.The results showed that XP-10 treatment reduced the number of tumor metastasis,enhanced the lymphocyte proliferation activity in Experimental Murine H22 Metastasis Models.However,XP-10 have no influence on organ index(spleen index and thymus index),CD3+CD4+T cells,CD44+CD62L effector T cells.Furthermore,compared with vehicle group,the expression of Treg cells(CD4+Foxp3+)and PD-1 were decreased in XP-10 treated group,but no variation on Th1 cells(CD4+IFN-?+)and Th17 cells(CD4+IL-17+),these results were consistent with the results from part1.These results suggested that XP-10 exerted therapeutic effect on pulmonary metastasis.Conclusion,polysaccharide composition from Aconitum brachypodum-XP-10 exerted a superior immunomodulating effects in vitro and in vivo,significantly suppressed pulmonary metastasis,the mechanism of action may be related to with inhibiting the expression of Treg cells,thus promoting T lymphocytes proliferation and anti-tumor immunological effect.This study will provide basis for the treatment of polysaccharide composition from Aconitum brachypodum in anti-tumor immunological therapy.