Suppression of the Purgative Action of Rhein Anthrone, the Active Metabolite of Sennosides A and B, by Indomethacin in Rats

Abstract

Rhein anthrone (12.48 mg kg-1) produces watery and mucoid diarrhoea approximately 20 min after intracaecal administration to rats. Pretreatment with the prostaglandin (PG) biosynthesis inhibitor indomethacin (10 mg kg-1, i.p.) only delayed and did not completely block the onset of the induced diarrhoea. Rhein anthrone stimulated PGE2 release into the rat colonic lumen and the increased release was depressed by indomethacin. Rhein anthrone also accelerated large intestinal transit and this acceleration could be partly inhibited by indomethacin, which was probably responsible for the delay in the onset of diarrhoea. Indomethacin prevented the enhanced water, K+ and mucus secretion and the reduced Na+ absorption in the colon which were induced by rhein anthrone. The net water secretion could not be reversed to net absorption and the mucus secretion was only slightly depressed by indomethacin. Thus, our findings suggest that other mechanisms, together with the PG-dependent mechanism, are involved in the purgative action of rhein anthrone in rats.

Laxative Effect of Agarwood Leaves and Its Mechanism

“…15,16) The mechanism involves the sennosides and their active derivatives acting on the intestinal mucosal epithelium and submucosal nerve bundles, thereby stimulating prostaglandin (PG) synthesis and endogenous acetylcholine release, and consequently enhancing the colonic smooth muscle contraction. [17][18][19] Unfortunately, the purgative activities of anthraquinoids (including senna) are too powerful for them to be regularly used, and even periodic use of these laxatives can induce pseudomelanosis coli, a risk factor for colorectal neoplasma. 3) Indeed, in the present study, the senna extract at 300 and 1000 mg/kg, p.o., had a strong laxative effect, and it induced severe diarrhea at the same doses as those Segments of the rabbit ileum were suspended at 1 g tension in an organ bath containing Tyrode's solution.…”

Tratamentos da compactação experimental do cólon maior de equinos com hidratação enteral, intravenosa e sene (Cassia augustifolia Vahl)

“…A sene está classificada entre os laxativos antranoides, derivados das antraquinonas, e tem como princípio ativo os senosídeos A e B. São farmacologicamente inativos, comportando-se como pró-drogas naturais. No cólon maior, os senosídeos são metabolizados pelas enzimas bacterianas da microbiota intestinal, originando a reinantrona, metabólito ativo responsável pelo efeito laxante (Lemli, 1988;Yagi et al, 1991).…”

Tratamento da compactação experimental do cólon maior em eqüinos: resultados de laboratório e exames bioquímicos

“…A sene está classificada entre os laxativos antranóides, derivados das antraquinonas, e tem como princípio ativo os senosídeos A e B. São farmacologicamente inativos, comportando-se como pró-drogas naturais. No cólon maior os senosídeos são metabolizados pelas enzimas bacterianas da microbiota intestinal, originando a reinantrona, metabólito ativo responsável pelo efeito laxante (Lemli, 1988;Yagi et al, 1991).…”