Pharmacological evaluation of 2-angeloyl ent-dihydrotucumanoic acid

Gymnosperma glutinosum (Spreng.) Less. (Asteraceae) is a bush used for the empirical treatment of pain, fever, and cancer. An ent-neo-clerodane diterpene (2-angeloyl ent-dihydrotumanoic acid; ADTA) was isolated from G. glutinosum.

This study evaluates the cytotoxic, anti-inflammatory, and antinociceptive effects of ADTA.

The cytotoxic effects of ADTA (1-350 μM) were evaluated using the MTT assay with human tumorigenic (SW-620, MDA-MB231, SKLU1, SiHa, and PC-3), and non-tumorigenic (HaCaT) cells for 48 h. The in vitro anti-inflammatory effects of ADTA (0.23-460 μM) were assessed using murine peritoneal macrophages stimulated with LPS and estimating the levels of pro-inflammatory mediators for 48 h. The antinociceptive effects of ADTA (25-100 mg/kg p.o.) were evaluated using two in vivo models of chemical-induced nociception during 1 h.

ADTA lacked cytotoxic activity (IC₅₀> 100 μM) on tumorigenic cells. In non-tumorigenic cells (HaCaT), ADTA exerted low cytotoxic effects (IC₅₀=273 μM). ADTA, at concentrations of 115 μM or higher, decreased the release of pro-inflammatory mediators. The maximum antinociceptive effects of ADTA in the acetic acid-induced abdominal constrictions by ADTA was found at 100 mg/kg (63%), whereas in the formalin test at phase 1 and phase 2, ADTA (100 mg/kg) decreased the licking time by 47 and 71%, respectively.

The results indicate that ADTA, obtained from G. glutinosum, exerts moderate in vitro anti-inflammatory and in vivo antinociceptive effects, but lacks cytotoxic effects on human cancer cells.