Pharmacological evaluation of 2-angeloyl ent -dihydrotucumanoic acid

Abstract

Context: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.Objective: This study evaluates the cytotoxic, anti-inflammatory, and antinociceptive effects of ADTA.Materials and methods: 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.Results: 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.Conclusion: 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.

Rapid and Simultaneous Extraction of Bisabolol and Flavonoids from Gymnosperma glutinosum and Their Potential Use as Cosmetic Ingredients

“…Most of the compounds isolated from G. glutinosum are methoxylated flavones such as 5,7-dihydroxy 3,6,8-trimethoxyflavone and 5,7-dihydroxy 3,6,8,2 ,4 ,5 -hexamethoxyflavone, and some ent-labdane-type diterpene [20][21][22][23]. More recent studies showed the isolation of a diterpene ent-labdene-type: ent-dihydrotumanoic acid (DTA) with antidiarrheal and antinociceptive effects [24][25][26]. However, even when this plant is used in the treatment of some skin problems, there are no studies about the relation between the isolated compounds and these diseases.…”

Synergism between Naproxen and Rutin in a Mouse Model of Visceral Pain

“…Plant extracts or plant‐derived compounds also exert similar or improved analgesic effects as compared to currently used analgesics, but with less adverse effects [Zapata‐Morales et al,; González‐Chávez et al, ]. Among the compounds currently used as analgesics that were obtained from plant origin are: the alkaloid morphine, isolated from Papaver somniferum L (Papaveraceae), tetrahydrocannabinols isolated from Cannabis sativa L (CannabaceaeMartinov), capsaicin obtained from Capsicum annuum L (Solanaceae) and Capsicum chinense Jacq (Solanaceae), salicilin isolated from Salix alba L (Salicaceae) and rutin, a glycoside flavonoid obtained from Ruta graveolens and other medicinal plants [Calixto, ; Sofic et al, ; Hamad, ].…”