THE SEARCH FOR MEDICINES FROM THE PLANTS OF MONTEVERDE
William M Setzerore than 3000 species of flowering plants
in 185 families are known from the Monte-
verde region (see Appendix 1). This bio-
logical diversity and selective pressure by herbivores
and parasites have led to the development of diverse
chemical defenses. Up to 10% of the dry weight of
plants can be made up of chemicals designed for de-
fense against infection or herbivory, including novel
substances that may be used as medicines or as start-
ing materials for the development of new drugs. De-
spite considerable research on natural products, the
medicinal potential of tropical plants has not been
exploited. Many species of tropical plants have never
been described, much less surveyed for biologically
active constituents.
Our research in Monteverde has focused on the
isolation, biological testing, and identification of po-
tentially useful natural products from the MCFP. We
pose three questions: (1) what potential new pharma-
copeia from natural sources might we uncover? (2)
How different is the chemistry of lower montane
plants from that of lowland tropical rain forest plants?
(3) Can we identify new potential alternative (and
ecologically less damaging) "cash crops" for critical
tropical habitats?
A starting point for these endeavors is local tra-
ditional medicine or ethnobotany of the aboriginal
population. Monteverde has little ethnobotanical tra-
dition to draw from; the aboriginal people apparently
did not live or farm in the cloud forests of this area
(see Timm, "Prehistoric Cultures"). The search for
tropical medicinal agents from Monteverde must in-
volve either a hit-or-miss approach or concentrate on
plant families that have active members from other
areas. We used both approaches.
Initially, we concentrated on the Araliaceae (Setzer
et al. 1992). Some members of this family (the "gin-
seng" family) have been used in traditional Oriental
medicine, notably members of the genera Panax (Hou
1978), Schefflera (Adam et al. 1982), and Acantho-
panax (Xie et al. 1989, Wang et al. 1991). We obtained
crude extracts from leaves of Dendropanax arboreus,
D. gonatopodus, D. latilobus, D. querceti, Schefflera
rodriqueziana, S. robusta, Oreopanax capitatus, O.
liebmanii, O. nubigenus, O. oerstedianus, O. standleyi,
and O. xalapensis and screened them for antimicro-
bial activity (fungicidal and bacteriocidal activity) and
for in vitro anticancer activity (cytotoxic activity
against a number of cancer cell lines in culture).
Chloroform extracts from three species (Oreopanax
standleyi, O. xalapensis, and especially Dendropanax
latilobus) showed antifungal activity. Crude ethanol
extracts of D. latilobus, D. arboreus, D. querceti, D.
gonatopodus, O. liebmanii, and O. xalapensis showed
remarkable cytotoxic activity against Hep G2 human
hepatocellular carcinoma cells, A-431 human epider-
moid carcinoma cells, H-4IIE rat liver hepatoma cells,
and L-1210 murine lymphocytic cells. These extracts
were not toxic to normal, nonproliferating cultures of
adult rat hepatocytes. The extract of D. arboreus was
non-toxic to normal liver cells.
The active component from D. arboreus was iso-
lated by activity-directed separation (Setzer et al.
1995b) using liquid chromatography (0.011% yield
based on weight of fresh leaves). The structure of the
cytotoxic material was determined by spectroscopic
techniques to be the acetylenic compound cis-1,9,16-
heptadecatrien-4,6-diyn-3,8-diol. This compound is
very toxic to tumor cells in culture (IC 50 values are in
the jig/ml range) but nontoxic to normal hepatocytes.
Similarly, bioactivity-guided isolation and structure
determination of the cytotoxic component of D. quer-
ceti revealed the active substance to be the relatively
common triterpenoid lupeol (W. Setzer, unpubl. data)The plant family Clusiaceae is also a rich source
of antibacterial substances. Sap from various Clusia
species showed bacteriocidal activity (W. Setzer, un-
publ. data). The crude ethanol extract from the leaves
of Tovomitopsis psychotriifolia exhibited antibacte-
rial activity against Bacillus cereus, Staphylococcus
aureus, and Pseudomonas aeruginosa. The biologi-
cally active agent in the extract has been isolated by
chromatographic techniques and identified by nuclear
magnetic resonance spectroscopy as the vitamin E452 Conservation BiologyM