Study On Anti-tumor And Antidepressant Effects And Mechanism Of Ergosterol And Its Derivatives

Ergosterol is an important mycophenolic sterol mainly found in yeasts,molds and other fungi and certain plants.Not only has a variety of pharmacological activities,but also has been widely used in the development of drugs.At present,the source of ergosterol is mainly synthesized by microbial fermentation and can also be obtained in the extraction of mycelia.In order to make more effective use of a fat soluble,the ergosterol derivative,enhance its multiple pharmacological activities were studied.In this experiment,self-made ergosterol derivatives(ErN,ErC,ErS,ErF and Er3F)were used for HPLC detection,and their anti-tumor and anti-depressant activities were studied to evaluate their related pharmacological mechanisms as the main research content.1.Study on the anti-tumor activity of ergosterol and its derivatives.First of all,a H22 transplanted tumor model was established to measure tumor weight,organ weight,serological parameters,tumor tissue section staining,and related proteins.After analyzing the data,the tumor inhibition rate,thymus,spleen and liver index,and tumor necrosis factor-alpha(TNF-α),interferon-γ(IFN-γ),interleukin-6(IL-6),vascular endothelial growth factor(VEGF)and liver Kidney indexes,aspartate aminotransferase(AST),alanine aminotransferase(ALT),urea nitrogen(BUN),creatinine(CRE),tumor tissue and spleen H&E staining,TUNEL staining,immunohistochemistry,and western blot,etc.Finally,the anti-tumor mechanism of ergosterol and its derivatives was found.The results showed that ergosterol and its derivatives can significantly inhibit the growth of solid tumors in H22 tumor-bearing mice.After administration,serum cytokines TNF-α and IFN-γ increased,while IL-6 and VEGF decreased.In addition,HE,TUNEL staining results we can find that ergosterol and its derivatives can promote apoptosis of tumor cells,after examination and comparison of various indicators found that the five kinds of derivatives in the anti-tumor effect of ErN,ErC times Then,the corresponding protein was detected in ErN tumor tissue.The anti-tumor activity of ErN was analyzed by immunohistochemistry and western blot.It was found that ErN could regulate the expression of protein and then play an anti-tumor effect.The mechanism may be related to the up-regulation of Bax,down-regulation of Bcl-2,VEGF.2.Study on the antidepressant activity of ergosterol and its derivatives.In order to eliminate the possibility that the immobility time in the forced swimming test(FST)was due to the possibility of motor activity interference,the mice were required to conduct free-activity experiments and the spontaneous activity of each mouse was observed in the ZZ-6 mouse autonomous activity test apparatus.After 3 minutes of adaptation,the number of activities recorded within 5 min was recorded.In the present study,it was used to evaluate antidepressant activity of drugs mainly through FST.The optimal dose of anti-depression of ergosterol and its derivatives was screened in the range of 0.1 mg/kg to 100 mg/kg in previous experiments.It was found that ergosterol and its derivatives showed some antidepressant activity in a mouse model of depression.However,the time of ErN reduction was the most obvious,and the effective dose and sub-effective dose were 5 mg/kg and 0.5 mg/kg respectively.Continued follow-up study found that ErN(0.5mg/kg)combined with tianeptin,reboxetine showed synergistic effect when combined with fluoxetine was no such effect.The anti-depressive effects of ErN(5 mg/kg)on FST in different central nervous systems showed that competitive GABA antagonist bicuculline(4 mg/kg ip)effectively blocked ErN(5 mg/kg,ip)antidepressant-like effect.We used NMDA(75 mg/kg,ip)as an excitatory amino acid agonist to prevent a decrease in immobility time induced by ErN(5 mg/kg,ip)treatment in FST,revealing that glutamatergic system participates in ErN Antidepressant effect.