Actions of octocoral and tobacco cembranoids on nicotinic receptors

Nicotinic acetylcholine receptors (AChRs) are pentameric proteins that form agonist-gated cation channels through the plasma membrane. AChR agonists and antagonists are potential candidates for the treatment of neurodegenerative diseases. Cembranoids are naturally occurring diterpenoids that contain a 14-carbon ring. These diterpenoids interact with AChRs in complex ways: as irreversible inhibitors at the agonist sites, as noncompetitive inhibitors, or as positive modulators, but no cembranoid was ever shown to have agonistic activity on AChRs. The cembranoid eupalmerin acetate displays positive modulation of agonist-induced currents in the muscle-type AChR and in the related gamma-aminobutyric acid (GABA) type A receptor. Moreover, cembranoids display important biological effects, many of them mediated by nicotinic receptors. Cembranoids from tobacco are neuroprotective through a nicotinic anti-apoptotic mechanism preventing excitotoxic neuronal death which in part could result from anti-inflammatory properties of cembranoids. Moreover, tobacco cembranoids also have anti-inflammatory properties which could enhance their neuroprotective properties. Cembranoids from tobacco affect nicotine-related behavior: they increase the transient initial ataxia caused by first nicotine injection into naive rats and inhibit the expression of locomotor sensitization to repeated injections of nicotine. In addition, cembranoids are known to act as anti-tumor compounds. In conclusion, cembranoids provide a promising source of lead drugs for many clinical areas, including neuroprotection, smoking-cessation, and anti-cancer therapies. (C) 2009 Elsevier Ltd. All rights reserved.

Antiprotozoan activity of Brazilian marine cnidarian extracts and of a modified steroid from the octocoral Carijoa riisei

In the present investigation, we have evaluated the antileishmanial and antitrypanosomal activity of methanolic crude extracts obtained from eight species of cnidarians and of a modified steroid isolated from the octocoral Carijoa riisei. The antileishmanial activity of cnidarians crude extracts showed 50% inhibitory concentration ( IC50) values in the concentration range between 2.8 and 93.3 mu g/mL. Trypomastigotes of Trypanosoma cruzi were less susceptible to the crude extracts, with IC50 values in the concentration range between 40.9 and 117.9 mu g/mL. The steroid (18-acetoxipregna-1,4,20-trien-3-one) displayed a strong antileishmanial activity, with an IC50 value of 5.5 mu g/mL against promastigotes and 16.88 mu g/mL against intracellular amastigotes. The steroid also displayed mammalian cytotoxicity (IC50 of 10.6 mu g/mL), but no hemolytic activity was observed at the highest concentration of 12.5 mu g/mL. The antileishmanial effect of the steroid in macrophages suggested other mechanism than macrophage activation, as no upregulation of nitric oxide was observed. The antitrypanosomal activity of the steroid resulted in an IC50 value of 50.5 mu g/mL. These results indicate the potential of cnidarian natural compounds as antileishmanial drug candidates.