Antigenotoxicity of trans-Dehydrocrotonin, a Clerodane Diterpene from Croton cajucara

Abstract

The antigenotoxic action of three doses of trans-dehydrocrotonin (t-DCTN), the active ingredient obtained from the bark extract of Croton cajucara, a plant native to the Amazon, was determined in Swiss mice in vivo. Mice were submitted to acute intraperitoneal and gavage treatments, then their bone marrow cells were subsequently analyzed by micronucleus (MN) and chromosome aberration (CA) assays. Comparisons were performed between the three doses of t-DCTN and the negative-control group. Statistical analysis indicated that doses of 50 and 75 % of the LD(50), via intraperitoneal treatment or gavage injection, were antimutagenic with regard to cyclophosphamide. However, the dose of 25 % of the LD(50) was only antimutagenic when administered by gavage. Based on these observations, it can be suggested that gavage is the most effective method of administering t-DCTN. In addition, t-DCTN showed no cytotoxic effects in the bone marrow cells regardless of the route of exposure.

Uma revisão das atividades biológicas da trans-desidrocrotonina, um produto natural obtido de Croton cajucara

“…Baseado nestas observações pôde-se concluir que a via oral é a mais adequada para administração da DCTN. Isto é relevante, pois esta é a via de uso popular do Croton cajucara (Agner et al, 2001). …”

“…Este 19-nor-clerodano mostrou correlação com grande parte das propriedades farmacológicas do Croton cajucara, tendo sido comprovado as seguintes atividades: hipoglicêmica (Farias et al, 1997;Silva et al, 2001a), hipolipidêmica (Silva et al, 2001a,b,c;Bighetti et al, 2004), antigenotóxica (Agner et al, 1999;Agner et al, 2001), antiulcerogênica (Rodríguez et al, 2004;SouzaBrito et al, 1998;Hiruma-Lima et al, 1999;Maciel et al, 2000), antitumoral (Maciel et al, 2000;Grynberg et al, 1999;Melo et al, 2004), antiinfl amatória e antinociceptiva (Maciel et al, 2002a;Carvalho et al, 1996), antiestrogênica (Luna Costa et al, 1999) e cardiovascular (Silva et al, 2005). Atualmente, a partir de modifi cações químicas da molécula de DCTN estão sendo desenvolvidos estudos que objetivam a avaliação da relação estrutura/atividade biológica Maciel et al, 2000;Grynberg et al, 1999;Melo et al, 2004;Anazetti et al, 2003;Anazetti et al, 2004;Melo et al, 2001).…”

Natural and semi-synthetic clerodanes of Croton cajucara and their cytotoxic effects against ehrlich carcinoma and human K562 leukemia cells

“…The hexane extract was chromatographed on a silica gel column with hexane affording fraction A; CH 2 Cl 2 (fraction B) and then, MeOH (fraction C). The MeOH extract was chromatographed with mixtures of hexane/EtOAc affording fr 1 (7:3), fr 2 (6:4), fr 3 (5:5), fr 4 (1:3) and fr 5 (0:1) and then with mixtures of EtOAc/MeOH to obtain two fractions [fr 6 (1:1) and fr 7 (0:1)]. The fractions fr 1 -fr 7 produced 26.3g of 1.…”

“…In addition, hypoglycemic, 8 antiatherogenic and hypolipidaemic effects 9 were also recorded. Clerodanes trans-crotonin (2), trans-cajucarin B (3), cis-cajucarin B (4), trans-cajucarin A (5), cajucarinolide (6) and isocajucarinolide (7) were previously isolated as minor compounds of the stem bark of Croton cajucara. 10,11 The cajucarinolides (6 and 7)…”

“…According to traditional folk medicine, clerodane trans-dehydrocrotonin (1) possesses striking correlation with therapeutic use of Croton cajucara and included among its biologic properties are antiinflammatory and antinociceptive, [1][2][3] antioestrogenic, 4 antigenotoxic 5,6 and antiulcerogenic 1,7 activities. In addition, hypoglycemic, 8 antiatherogenic and hypolipidaemic effects 9 were also recorded.…”