Ursolic acid and other pentacyclic triterpenoids stimulate intestinal alkaline sphingomyelinase in vitro

Purpose: Alkaline sphingomyelinase (alk-SMase) is an enzyme that hydrolyses sphingomyelin in a bile salt-dependent manner in the gastrointestinal tract, and has been proposed as an inhibitor of colon carcinogenesis. Ursolic acid (UA) is a plant-derived pentacyclic triterpenoid that has been shown to have anti-proliferative and apoptotic effects on HT29 human colon adenocarcinoma cells, with activation of alk-SMase as an early event. The aim of this study was to study the in vitro effects of UA and its analogues on the activity of purified rat intestinal alk-SMase. Methods: Rat intestinal alk-SMase activity was determined after incubation with UA in the presence and absence of taurocholate (TC). The effect was compared with boswellic acids, another group of pentacyclic triterpenoids. Results: UA enhanced the activity of rat intestinal alk-SMase in a dose-dependent manner, without a similar effect on bacterial neutral SMase. Four types of boswellic acid also increased the enzyme activity, with the effect of acetyl-keto-beta-boswellic acid being most potent. Activation of alk-SMase by TC; at a low concentration (0.4 mM), but not at a high concentration, was enhanced by UA. Conclusions: Ursolic acid and four types of boswellic acid, all pentacyclic triterpenoids, have a stimulatory effect on the activity of intestinal alk-SMase.