A Bioactive Spirolactone Iridoid and Triterpenoids from Himatanthus sucuuba.

Abstract

Himatanthus sucuuba, SPRUCE (M. ARG.) WOODSON (Apocynaceae) ("Bellaco-Caspi"), a tree from the Amazon rain forest, has received much attention in the literature for the treatment of various ailments, although the ethnobotanical information is somewhat contradictory. For example, in Perú, an infusion from the stem bark has been used as wound-healing agent, for the treatment of tumors, boils and swellings, against arthritis, as a vermifuge laxative, 1) and as hallucinogen.2) In Brazil, on the other hand, the dried bark is alleged to have anti-ulcer and aphrodisiac activities whereas the latex is used as an antitumor agent.3) The Caboclos in the Amazon use the dried stem bark for its analgesic and anti-tussive activities. 4) In Colombia, the root is said to be very poisonous. 5)The toxicity of the reproductive system and teratogenic potential of the stem bark have been investigated. 6) Recently, two lichen depsides found in the bark of H. sucuuba, have shown inhibition against monoamine oxidase-B.7) The in vivo cicatrizant activity of H. sucuuba has been investigated by our group. Although, in an initial experiment, an extract of the bark of H. sucuuba showed significant cicatrizant activity, this result could not be reproduced in subsequent runs.8) An acute toxicity screening-after i.p. administration of 0.1 to 1 mg of extract per gram of mouse weight-determined that H. sucuuba was non-toxic in this range.As part of our systematic search for potential anti-cancer agents from plants, 9) an extract of the bark of H. sucuuba underwent a mechanism-based bioassay fractionation. Our assay uses engineered yeasts which lack the RAD52 DNA repair pathway, one of the three major DNA repair pathways that have been defined in yeast, and may also lack the gene for topoisomerase I.10) An extract which inhibits these yeast mutants to a greater extent than it inhibits the wild-type strain RS188N is thus expected to contain agents which induce DNA damage. Results and DiscussionThe ethanolic extract of the bark of H. sucuuba [IC 12 ϭ 4000 mg/ml (RS321)] was partitioned between hexane and 80% aq. methanol, resulting in enhanced activity in the latter fraction. Further partitioning (60% aq. methanol/CH 2 Cl 2 ) concentrated the activity in the dichloromethane fraction (IC 12 ϭ380 mg/ml). Chromatographic purification of this fraction led to the isolation of a known iridoid lactone, plumericin (1), 11) responsible for the DNA damaging activity of the extract. The activity observed was relatively weak, with an IC 12 value of 70 mg/ml for the RS321 yeast strain. For comparison purposes, the known active agent streptonigrin 12) has an IC 12 value of 0.65 mg/ml against RS321. Compound 1 is a known antifungal which has been isolated previously from H. sucuuba 7) and other Himatanthus species.13)The non-polar (hexane) fraction was investigated for its in vitro differential cytotoxic activity using various cancer cell lines (H460, ME180, DU145, MCF-7, HT29). The resulting 50% growth inhibition (GI 50 ) values were greater than the control (BA...

Antibacterial and antifungal activity of extracts and exudates of the Amazonian medicinal tree Himatanthus articulatus (Vahl) Woodson (common name: sucuba)

“…Himatanthus articulatus (Vahl) Woodson (Apocynaceae) is a tree found in Panama, Colombia, Peru, Bolivia, Venezuela, Guyana, Suriname, French Guiana and in the savannah regions of the state of Roraima (RR), in the northern Brazilian Amazon (Milliken 1995, Wood et al 2001, Mobot 2007 (Elizabetsky & Castilhos 1990) and are important agents in the treatment of blood parasites such as Trypanosoma cruzi and Leishmania donovani (Mesquita et al 2005). Antitumor and aphrodisiac properties have been reported for the latex derived from sucuba, which is typically diluted in water and administered orally (Van den Berg 1984).…”

“…According to the phytochemical literature, many of these polar com-pounds have been reported in Himatanthus spp. (AbderKadel et al 1997, Veloso et al 1998, Wood et al 2001, Souza et al 2004, Mesquita et al 2005. Furthermore, the fact that low (hexane) and medium (ethyl acetate) polarity extracts displayed no inhibitory activity whatsoever further points to the probable polar nature of antifungal and antibacterial substances present in H. articulatus.…”

“…Himatanthus articulatus (Vahl) Woodson (Apocynaceae) is a tree found in Panama, Colombia, Peru, Bolivia, Venezuela, Guyana, Suriname, French Guiana and in the savannah regions of the state of Roraima (RR), in the northern Brazilian Amazon (Milliken 1995, Wood et al 2001, Mobot 2007. In Brazil, H. articulatus is known by the common name sucuba and is therapeutically one of the most widely-used medicinal plants in the northern Amazon Region.…”

Himatanthus lancifolius (Müll. Arg.) Woodson, Apocynaceae: estudo farmacobotânico de uma planta medicinal da Farmacopeia brasileira 1ª edição

“…Os alcaloides indólicos dos representantes do gênero apresentam diversas atividades farmacológicas, entre elas antimicrobiana (Silva et al, 1998;Neto et al, 2002;Morel et al, 2006), antitumoral (Wood et al, 2001), antiprotozoária (Deharo et al, 2001;Mesquita et al, 2005;Castillo et al, 2007) e anti-inflamatória (Miranda et al, 2000). Himatanthus lancifolius (Müll.…”

The Inhibition of Superoxide Anion Generation by Neutrophils from Viscum articulactum

“…Therefore, C-2 of 2 was also assigned the S-configuration. 9) On the basis of the above results, the structure of compound 2 was established to be (2S)-pinocem- 13) vanillin (9), 14) methylparaben (10), 13) p-hydroxy-benzoic acid (11), 13) protocatechuic acid (12), 15) 4-b-D-glucosyloxy-3-hydroxy-benzoic acid (13), 16) 2-phenylethanol (14), 17) cinnamic acid methyl ester (15), 18) 4-O-cinnamoyl quinic acid (16), 19) b-amyrin acetate (17), 20) oleanolic acid (18), 21) lupenyl acetate (19), 22) and 2-deoxy-epi-inositol (20) 23) were also isolated and identified by comparison of their spectral data with corresponding literature values.…”