Isolation of a Dihydrobenzofuran Lignan from South American Dragon's Blood (Croton spp.) as an Inhibitor of Cell Proliferation

Abstract

Dragon's blood is a red viscous latex extracted from the cortex of various Croton spp. (Euphorbiaceae), most commonly Croton lechleri, Croton draconoides (or Croton palanostigma), and Croton erythrochilus. It is used in South American popular medicine for several purposes, including wound healing. Bioassay-guided fractionation of dragon's blood, using an in vitro test system for the stimulation of human umbilical vein endothelial cells, has resulted in the isolation of a dihydrobenzofuran lignan, 3',4-O-dimethylcedrusin or 4-O-methyldihydrodehydrodiconiferyl alcohol [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-methoxybenzo furan-5- propan-1-ol] [1] as the biologically active principle. A related compound, 4-O-methylcedrusin [2-(3',4'-dimethoxyphenyl)-3-hydroxymethyl-2,3-dihydro-7-hydroxybenzo furan-5- propan-1-ol] [2], and the alkaloid taspine [3], also isolated from dragon's blood, were not active in the same assay. A cell proliferation assay, measuring the incorporation of tritiated thymidine in endothelial cells, showed that compound 1 did not stimulate cell proliferation, but rather inhibited thymidine incorporation, while protecting cells against degradation in a starvation medium.

Novel Derivative of Benzofuran Induces Cell Death Mostly by G2/M Cell Cycle Arrest through p53-dependent Pathway but Partially by Inhibition of NF-κB

“…3Ј,4-di-O-methylcedrusin or 3-[2-(3,4-dimethoxyphenyl)-3-hydroxymethyl-7-methoxy-2,3-dihydro-1-benzofuran-5-yl]propan-1-ol 5 is one of the naturally occurring active principals of latex and has been used as an inhibitor of tumor cell proliferation (17,18). A dihydrobenzofuran lignan derivative has been identified as a potential antiproliferative and antitumor agent (19).…”

Inducción de la formación de moco gástrico por sangre de grado (Croton palanostigma)

“…Está ya documentado el efecto cicatrizante de la sangre de grado ( 7 ), así como el efecto de la taspina sobre la migración celular y síntesis de colágeno, también demostrados ( 15,16 ). Sin embargo, para en el tratamiento de la gastritis y Tabla 2.-pH del jugo gástrico de ratas tratadas con sangre de grado de Croton palanostigma gástrico y duodenal.…”

Actividad antibacteriana de la Sangre de Grado (Croton lechleri) frente al Helicobacter pylori.

“…Estudios anteriores han mostrado que la sangre de grado tiene efecto positivo en el tratamiento de las ulceras gástricas y la gastritis (13,14,15,16,17,18,19,20,21,22,23,24). La actividad curativa estaría relacionada con el efecto cicatrizante del Clorhidrato de Taspina, producto de la estimulación en la migración de los fibroblastos, como ha sido probada por Málaga y Vaisverg respectivamente (27).…”

“…El alcaloide Taspina ha sido documentado como cicatrizante, antiinflamatorio, actividad contra el desarrollo de sarcomas y acción antiviral (específicamente contra Herpesvirus) (23). Varios estudios entre 1991 y 1993 también le confieren propiedades antitumorales in vitro (24).…”