摘要
Abstract
Objective To investigate the effects of trahydrocurcumin on immune function and antioxidant capacity in S180 tumor bearing mice.At the same time,preliminary exploration of the non-clinical safety characteristics of different formulation technologies.Methods The nude mice were divided into a normal control group,a tumor bearing model group,a cyclophosphamide group(CTX),and a tetrahydrocurcumin group(THC).After constructing the S180 tumor bearing model,the THC group was given 200 mg·kg-1 tetrahydrocurcumin suspension,the CTX group was given 20 mg·kg-1 cyclophosphamide,and the normal control group and tumor bearing group were given equal volumes of 5％CMC Na for 15 consecutive days.The tumor growth,immune response,and oxidative stress levels of each group were compared;Formulations were prepared using ordinary suspensions or solid dispersions,and preliminary non clinical safety studies were conducted in rats to compare the general toxicological characteristics of different formulations.Results The tumor volume and weight of the THC group were significantly lower than those of the tumor bearing model group(P＜0.05).The thymus and spleen indices of mice were significantly increased,and IL-2,TNF-α,and IFN-γ were significantly higher than those of the tumor bearing model group(P＜0.05).The proportion of CD4+T cells in animals was significantly increased,and the proportion of CD8+T cells was significantly decreased(P＜0.01),indicating that THC can significantly promote the infiltration and activation of T cells into the tumor microenvironment;The levels of serum SOD and GSH Px in the THC group were higher than those in the other groups,while the levels of MDA and LDH were significantly lower than those in the model group(P＜0.05).The expression levels of Nrf2 and HO-1 proteins in THC tumor tissue were significantly lower than those in the tumor bearing model group(P＜0.01).In the exploratory toxicity test of repeated 4-week administration in rats,it was observed that solid dispersion technology formulations have higher safety characteristics.Conclusion Tetrahydro curcumin has a dose-dependent inhibitory effect on tumor growth,and its anti-tumor mechanism may be related to enhancing the antioxidant capacity of tumor bearing mouse tissues,promoting T cell infiltration and activation into the tumor microenvironment.Compared with conventional suspension formulations,the formulation of tetrahydrocurcumin developed using solid dispersion technology has higher safety characteristics.关键词
四氢姜黄素/抗肿瘤/免疫应答/抗氧化/氧化应激/非临床安全性/固体分散体技术Key words
Trahydrocurcumin/Anti-tumor/Immune response/Antioxidation/Oxidative stress/Non-clinical safety/Solid dispersion technology分类
医药卫生
