Abstract:

Objective To explore the pharmacological mechanism of ethanol extract from polygonatum odoratum against colorectal cancer（CRC）via regulating immunometabolism. Methods Twenty ⁃five mice were divided into a blank control group，CRC model group and CRC + polygonatum odoratum ethanol extract treatment group. The mice in CRC + polygonatum odoratum ethanol extract treatment group received intraperitoneal injection of polygonatum odoratum ethanol extract at a concentration of 1 g/kg，2 g/kg，or 3 g/kg，respectively，while mice in the blank control group and the CRC model group received intraperitoneal injection of equal volume of normal saline. After 8 weeks of continuous administration，peripheral blood NK cell killing activity and levels of interleukin ⁃2（IL⁃2），interleukin⁃12（IL⁃12）and tumor necrosis factor⁃α（TNF⁃α）were measured in each group. Organ indexes were calculated and colorectal tumor formation was observed. Results The peripheral blood NK cell killing activity was significantly lower in the CRC model group than in the blank control group. After treatment with polygonatum odoratum ethanol extract，the NK cell killing activity was significantly enhanced as compared with that in the CRC model group（P < 0.05），having the highest level in the high⁃dose group，followed by the medium⁃ dose group，and then the low⁃dose group. Peripheral blood levels of IL⁃2，IL⁃12 and TNF⁃ α were significantly decreased in the CRC model group as compared with those in the blank control group（P < 0.05），while polygonatum odoratum ethanol extract significantly up⁃regulated serum levels of IL⁃2，IL⁃12 and TNF⁃α as compared with the CRC model group（P < 0.05），and levels of three indicators were the highest in the high⁃dose group，followed by themedium⁃dose group，and were the lowest in the low⁃dose group（P < 0.05）. Cardiac and liver indexes did not differ statistically between the CRC model group and the polygonatum odoratum ethanol extract treatment group（P > 0.05），while the indexes of spleen and thymus in the polygonatum odoratum ethanol extract treatment group were significantly increased as compared with those in the model group（P < 0.05），and the increase was the most significant in the high⁃dose group，followed by the medium⁃dose group，and was the least in the low⁃dose group （P < 0.05）. Anatomical experiments showed that tumor and other abnormal hyperplasia were observed in colon and rectum in the model group，while the number of tumor and other abnormal hyperplasia was significantly reduced after treatment with polygonatum odoratum ethanol extract at different concentrations［（8.83 ± 0.71）vs.（4.68 ± 0.46）vs.（3.41 ± 0.78）vs.（2.13 ± 0.53），F = 65.642，P < 0.001］. Conclusions Ethanol extract from polygona⁃ tum odoratum may play an anticancer role by reducing colorectal tumor number and hyperplasia through regulating immunometabolism.

Key words:

colorectal cancer, polygonatum odoratum ethanol extract, immunometabolism, pharma? cological mechanism study