Influence of a Highly Purified Senna Extract on Colonic Epithelium

Abstract

Background: Chronic use of sennoside laxatives often causes pseudomelanosis coli. A recent study suggested that pseudomelanosis coli is associated with an increased colorectal cancer risk. A single high dose of highly purified senna extract increased proliferation rate and reduced crypt length in the sigmoid colon compared to historical controls. Aims: To evaluate in a controlled study the effects of highly purified senna extract on cell proliferation and crypt length in the entire colon and on p53 and bcl-2 expression. Methods: Addition of a senna extract to colonic lavage was studied in 184 consecutive outpatients. From 32 randomised patients, 15 with sennosides (Sen), 17 without (NSen), biopsies were taken. Proliferative activity was studied in 4 areas of the colon, using 5-bromo-2′-deoxyuridine labelling and immunohistochemistry (labelling index, LI). Expression of p53 and bcl-2 in the sigmoid colon was determined immunohistochemically. Results: Crypts were shorter in Sen than in NSen in the transverse and sigmoid colon. LI was higher in Sen than in NSen in the entire colon. No difference in p53 expression was seen. Bcl-2 expression was higher in both groups when crypts were shorter and/or proliferation was increased. Conclusion: Sennosides induce acute massive cell loss probably by apoptosis, causing shorter crypts, and increased cell proliferation and inhibition of apoptosis to restore cellularity. These effects may reflect the mechanism for the suggested cancer-promoting effect of chronic sennoside use.

Chronic Constipation: An Evidence-Based Review

“…182 Similar data in humans are lacking, except for one study that showed increased ACF after a single high dose of senna colonic lavage. 183 A prospective study of 1095 patients reported an increased relative risk of 3.04 for colorectal cancer as a result of anthraquinone laxative abuse. 184 Similarly, a retrospective study of 3049 patients who underwent colonoscopy revealed a higher incidence of Melanosis coli in patients diagnosed with colonic adenomas 184 (which are not necessarily malignant).…”

Is Senna Laxative Use Associated to Cathartic Colon, Genotoxicity, or Carcinogenicity?

“…As has already been indicated, the chronic use of sennoside laxatives on some occasions causes pseudomelanosis coli [40] and this has been associated to an increase in the risk of colorectal cancer [41]. In patients subjected to enemas containing senna extracts, it was observed that the sennosides induce an acute massive loss of intestinal cells, possibly because of apoptosis, and alter the length of the colonic crypts causing the appearance of shorter crypts and an increase of the cellular proliferation and inhibition of the restoring apoptosis of the cellular function.…”

“…In patients subjected to enemas containing senna extracts, it was observed that the sennosides induce an acute massive loss of intestinal cells, possibly because of apoptosis, and alter the length of the colonic crypts causing the appearance of shorter crypts and an increase of the cellular proliferation and inhibition of the restoring apoptosis of the cellular function. These effects could be the basis of the mechanism that would explain a supposed cancer promoter effect of the chronic use of sennosides [40]. It has been proven that the sennosides administered in an acute manner induce apoptosis of the epithelial cells of the colon, supposedly through the protein p53 “genome guardian,” mediated by p21/WAF, which results in shorter crypts.…”

In vitro Cytokine Expression by Peripheral Mononuclear Cells in Herbal Drug-induced Skin Eruption

“…The IL-4 primers used were: 5'-ATGGGTCTCACCTCCCAACTGCT-3' (forward) and 5'-CGAACACTTTGAATATTTCTCTCTCAT-3' (reverse). The IL-5 primers used were: 5"-GCTTCTGCATTT-GAGTTTGCTAGCT-3' (forward) and 5--TGGCCGTCAATG-TATTTCTTTATTAAG-3" (reverse) (8). The RANTES primers used were: 5'-ATATTCCTCGGACACCACAC -3' (forward) and 5'-CACTCCAGCCTGGG GAAGG -3" (reverse).…”