The mechanism of action of anthranoids in general and of sennosides at
the cellular level is not precisely known. Pseudomelanosis or pseudol
ipofuscinosis, a condition characterized by the accumulation of pigmen
ted macrophages in the lamina propria, is one of the well-known effect
s of these products. It is most probably the result of an interaction
between apoptotic epithelial cells and the lamina propria cellular inf
iltrate. Treatment of cell suspensions of intestinal epithelial cells
and of human intestinal epithelial cells in culture with rhein anthron
e, the active compound of sennosides, demonstrates a direct influence
of the drug on these epithelial cells. Low doses induce alterations in
cellular shape and organelles consistent with increased metabolism. H
igh doses induce apoptotic changes. The interaction between the epithe
lial cells and cells of the monocyte/macrophage lineage induces also t
he release of prostaglandins of the E series as shown by experiments o
n cell cultures of epithelial cells and peripheral blood cells. An inc
rease of PGE2 release to about 140% of the control value is noted foll
owing administration of low doses of rhein anthrone to a combination o
f human intestinal epithelial cells and human peripheral blood mononuc
lear cells. This finding indicates that rhein anthrone is activating c
ellular components of the intestinal immune system and may by this pat
hway induce secretion and motility.