title: Pharmacological evaluation of 2-angeloyl ent-dihydrotucumanoic acid.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Facultad de Ciencias Químicas , Universidad Autónoma de San Luis Potosí , San Luis Potosí , México.
authors.forename: Marco Martin
authors.initials: MM
authors.lastname: González-Chávez
authors.affiliation: b Facultad de Química , Universidad Autónoma de Yucatán , Mérida , México.
authors.forename: Victor
authors.initials: V
authors.lastname: Arana-Argáez
authors.affiliation: c Departamento de Farmacia, División de Ciencias Naturales y Exactas , Universidad de Guanajuato , Noria Alta , Guanajuato , 36050 , Guanajuato México.
authors.forename: Juan Ramón
authors.initials: JR
authors.lastname: Zapata-Morales
authors.affiliation: c Departamento de Farmacia, División de Ciencias Naturales y Exactas , Universidad de Guanajuato , Noria Alta , Guanajuato , 36050 , Guanajuato México.
authors.forename: Ana Karen
authors.initials: AK
authors.lastname: Ávila-Venegas
authors.affiliation: c Departamento de Farmacia, División de Ciencias Naturales y Exactas , Universidad de Guanajuato , Noria Alta , Guanajuato , 36050 , Guanajuato México.
authors.forename: Angel Josabad
authors.initials: AJ
authors.lastname: Alonso-Castro
authors.affiliation: d Facultad de Odontología , Universidad Autónoma de Baja California , Mexicali , Mexico.
authors.forename: Mario
authors.initials: M
authors.lastname: Isiordia-Espinoza
authors.affiliation: e Departamento de Química Orgánica , Instituto de Química, Universidad Nacional Autónoma de México , Ciudad de México , México.
authors.forename: Roberto
authors.initials: R
authors.lastname: Martínez
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D045785:Diterpenes, Clerodane / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: C000614678:2-angeloyl ent-dihydrotumanoic acid; D000700:Analgesics; D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D045785:Diterpenes, Clerodane
keywords: Gymnosperma glutinosum; antiinflammatory; antinociceptive