Study on the Toxic-Effect Relationship of Croton tiglium L.oil in the Treatment of Cold Accumulation Constipation / 世界科学技术-中医药现代化

ABSTRACT

Objective To explore the therapeutic effect and toxicity of Croton tiglium L.(croton)oil on rats with cold accumulation constipation,and to clarify the toxic-effect relationship of croton oil in the treatment of cold accumulation constipation.Methods The rats were orally treated with 10%2℃activated carbon solution for 3 consecutive days to replicate the model of cold constipation.The rats were fed with croton oil on the fourth day,and then the time of first defecation and the number of defecations within 3 h were observed and recorded.HE staining was used to evaluate the general pathological conditions of the colon tissues of rats.The serum levels of interleukin(IL)-6,IL-10,tumor necrosis factor(TNF)-α,cyclooxygenase(COX)-2,macrophage inflammatory protein(MIP)-1,alanine aminotransferase(ALT),aspartate aminotransferase(AST),and total protein(TP)were detected.Immunohistochemistry was used to detect the expression of myeloid differentiation factor 88(MyD88)and nuclear transcription factor(NF)-κB P65 in colon tissues of rats.Results Croton oil could shorten the time of first defecation and increase the number of defecations within 3h in rats with cold accumulation constipation to varying degrees,and the 3.78,2.83,and 1.89 g·kg-1 croton oil group had significant statistical significance(P<0.05).HE staining results showed that compared with the model group,croton oil group could cause different degrees of inflammation and focal necrosis,goblet cell loss and lamina propria edema in the colon tissue of rats,and the 3.78 g·kg-1 croton oil group was the most serious in the colon tissue injury.In addition,compared with model group,croton oil group could increase the levels of COX-2,TNF-α and IL-6 in serum to varying degrees(P<0.05),and 3.78 g·kg-1 croton oil group had the most obvious effect.The level of MIP-1 in serum was increased in croton oil group,and the effect was significant in 3.78 g·kg-1 croton oil group(P<0.01).But croton oil group had no significant effect on serum IL-10 level of rats.The immunohistochemical results showed that the protein levels of MyD88 were increased in croton oil dose groups except 0.05 dose group,and there were significant differences in 3.78,2.83,and 1.89 g·kg-1 dose groups(P<0.05).The expression level of NF-κB p65 was enhanced in the colon of rats after croton oil treatment,and there was significant difference in 3.78 g·kg-1 croton oil group(P<0.05).In addition,compared with model group,croton dose groups had no changes in organ indexes of heart,spleen,lung,kidney and thymus(P>0.05),while liver organ indexes in1.89 and 0.94 g·kg-1 croton oil groups were significantly increased(P<0.05).The results of liver biochemical indexes showed that croton oil group did not increase the contents of ALT,AST,and TP in serum of rats,and the differences were not statistically significant(P>0.05).Conclusion Croton oil can exert a dose-dependent purgative effect at 3.78,2.83,and 1.89 g·kg-1,but it also induced colonic mucosal injury in rats by regulating the inflammatory response mediated by the MyD88/NF-κB pathway.At 0.94 and 0.47 g·kg-1,croton oil almost did not cause colon tissue injury in rats,but it had a weak purgative effect at this dose,suggesting that the best concentration range of croton oil in the treatment of cold accumulation constipation may be between 0.94 and 1.89 g·kg-1.