Laxative Effects of Total Diterpenoids Extracted from the Roots of Euphorbia pekinensis Are Attributable to Alterations of Aquaporins in the Colon.
This study was designed to evaluate the toxic effects of total diterpenoids extracted from the roots of Euphorbia pekinensis (TDEP) on the mouse colon and to clarify the mechanism. Dried powdered roots of E. pekinensis were extracted with chloroform, and then the extract (6.7 g) was subjected to column chromatography and preparative TLC, giving TDEP. Using the HPLC-DAD method, the purity of TDEP was determined as 85.26%. Mice were orally administered with TDEP (3.942, 19.71 and 39.42 mg/kg), after which fecal water content and colon water content were examined. Both of them increased over time after TDEP administration, accompanied by severe diarrhea. Three hours after TDEP administration, the animals were sacrificed to obtain their colons. The mRNA and protein expression levels of aquaporin 1 (AQP1), AQP3 and AQP4 in the colon were measured using real-time RT-PCR and Western blotting, respectively. TDEP significantly increased the levels of AQP3 and AQP4, but decreased that of AQP1 in dose-dependent manners. Similarly, Pekinenin C, a casbane diterpenoid, significantly increased AQP3 protein and mRNA expressions in human intestinal epithelial cells (HT-29). Histopathological examination revealed that the colon was not significantly damaged. The laxative effects of E. pekinensis were associated with the alterations of AQPs in the colon by TDEP.
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. wjwkl@126.com.
Kuilong
K
Wang
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. gyhliulian@163.com.
Lian
L
Liu
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. 18260028133@163.com.
Jianyu
J
Huang
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. whao5795@163.com.|Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China. whao5795@163.com.|Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing 210023, China. whao5795@163.com.|State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. whao5795@163.com.
Hongli
H
Yu
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. whao5795@163.com.|Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China. whao5795@163.com.|Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing, Nanjing 210023, China. whao5795@163.com.|State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. whao5795@163.com.
Hao
H
Wu
Jiangsu Key Laboratory of Chinese Medicine Processing, Nanjing University of Chinese Medicine, Nanjing 210023, China. xiaobingcui@163.com.
Yu
Y
Duan
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. xingde2293@126.com.|State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. xingde2293@126.com.
Xiaobing
X
Cui
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. liuliping1487@163.com.|State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. liuliping1487@163.com.
Xingde
X
Zhang
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. zhonglixunta349@163.com.
Liping
L
Liu
School of pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. duanyu1681@sina.com.
Wei
W
Wang
D000818:Animals; D020346:Aquaporins / Q000235:genetics / Q000378:metabolism*; D003106:Colon / Q000378:metabolism*; D004224:Diterpenes / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D028481:Euphorbia / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D054368:Laxatives / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry
D020346:Aquaporins; D004224:Diterpenes; D054368:Laxatives; D010936:Plant Extracts
Euphorbia pekinensis; aquaporins; diterpenoids; laxative effects