Nitric oxide production by several cytotoxic sterols and triterpenes

Nitric oxide (NO) has been identified as the major active molecule involved in the destruction of tumor cells by activated macrophages. Then, we decided to evaluate the NO production, both in LPS-activated and resting macrophages, by several cytotoxic sterols and triterpenes isolated by our group [1].

The compounds tested were: argentatins A (1) and B (2) isolated from Parthenium argentatum, and peniocerol (3), macdougallin (4) and chichipegenin (5) isolated from Myrtillocactus geometrizans.

The results showed that 1 and 2 inhibited, in a dose-dependent fashion, the NO production both in activated and resting macrophages. At 100µM, in the highest dose tested, 1 showed 63% of inhibition in the activated macrophages and 41% in the resting macrophages. In similar way 2 showed 63% and 41% of inhibition respectively.

On the other hand, 3 increased by 61% the NO production in resting macrophages and 59% in activated macrophages, both at 1×10^-5 M dose. While 4 and 5 were inactive at 1–10µM range dose, at higher dose they were cytotoxic to the macrophages.

These results clearly showed that there is not a relationship between the structures of sterols or triterpenes tested and their inhibition or stimulation of NO production in both activated and resting macrophages.

References: 1. Flores-Rosete, G. et al (2008) Nat. Prod. Comm. 3:413–422.