The Immuno-pharmacological Activity Of Beauvericin

Stiff Silkworm is a commonly used Chinese medicine. It comes from the silkworm infected by Beauveria Vuillemin, which has the effect of moistening the lung and eliminating phlegm. Beauvericin is a cyclic peptide extracted from the Stiff Silkworm. Early studies found that the compound had some anti-tumor activity in vivo, but the immune activities of beauvericin haven’t been reported.In the first chapter, it is designed to investigate the protective effect of beauvericin on the TNBS-induced inflammatory bowel disease model in mice. Here we demonstrated that high doses of beauvericin significantly alleviate various symptoms resulted from colitis, such as:body weight loss, animal death and diarrhea. As well, the irrgular expression of cytokines and signal molecular such as:TNF-a, IFN-y, IL-1β and IL-12have been restored. And in most experiments, beauvericin have better effect than the same dose of dexamethasone and its analogue is widespread used in the treatment of inflammatory bowel disease.In the next chapter, we continuously examined the activity of beauvericin. We find that beauvericin can significantly inhibit concanavalin induced proliferation of mice lymphocytes, while it has same effect on vitality of normal cells. Then we investigate its potency on cell apoptosis and cell cycle, not unexpected, we find beauvericin can progress the cell apoptosis by decrease the mitochondria membrane potential and increase the cytochrome c release, furthermore, beauvericin also induces cell-cycle arrest by regulating various kinds of cell-cycle related proteins.In conclusion, we have firstly reported that beauvericin has protective effect on TNBS induced colitis in mice. By comparing the potency of beauvericin, and its analogue reported effective on colitis, we find beauvericin have better effect than the positive drugs. We also firstly reported that beauvericin can significantly inhibit T-cell proliferation by both increasing cell apoptosis and arresting cell-cycle. All these results reveal that the advantage of beauvericin on immune disease therapy, from which is resulted from various ingredients with multi-activities, and our research also demonstrated that beauvericin, a new type of cyclic peptide, may be used as immunosuppressant for the treatment of colitis.