Molecular Mechanism Of Diarrhea Induced By Senna Through Aquaporins

Senna is commonly used as a laxative in clinics,but its long-term usage might result in some side effects.It is still unclear with toxic substances and molecular mechanism.In this study,SD rats and cell experiments were used to study the laxative functions and toxic actions for senna extract(SE),senna sennosides(SS)and sennoside A(SA).Regarding to rat behavior,clinical signs,organ index,pathological examination and gene expression levels of aquaporin family(Aqp1,Aqp2,Aqp3,Aqp4,Aqp5,Aqp6,Aqp7,Aqp8,Aqp9 and Aqp11),a series of technologies were used including qRT-PCR,western blot,H&E stain etc.Its purgative effect and potential toxicity.The expression profiles of Aqp in six organs including colon,kidney,liver,spleen,lung and stomach were constructed by qRT-PCR.The change curve of Aqp was characterized by principal component analysis.The in vivo experiments showed that the rats treated with the SE for 7 days had significantly decrease on body weight(p < 0.001),significantly increase on kidney index and liver index(p <0.001)and significantly increase with the expression of Aqps in kidney and liver.While the rats treated with the SS for 7 days had no significant difference in body weight,significantly increase on colon index(p < 0.01)and significantly decrease with the expression of Aqps in colon.PCA indicated that the SE rats were far different from the control rats with the Aqps expression in liver and kidney while the SS rats was far from the control with the Aqps expression in colon and spleen.These results suggested that SE treatment could result in more actions on kidney and liver.While the SS treatmentcould result in more actions on colon.It is suggested that abnormal expression of Aqp can be used as bio-markers to evaluate toxicities of drugs on the organs.In cell line assays,we investigated the actions of metabolites mixtures produced by the SE and SS being cultured in our in vitro intestinal solution.Both metabolites mixtures could inhibit the growth and induce apoptosis and autophagy in NCM460 and LoVo cells.We presumed that this might be one of the mechanisms of resulting in tissue damage and side effects.This method provides a new way to study traditional Chinese medicine at the cellular level.