Abstract
Glaucolide B is a sesquiterpene lactone isolated from Vernonia eremophila Mart. (Vernonieae, Asteraceae) and has schistosomicidal, antimicrobial and analgesic activities. This study examined the cytotoxic and clastogenic activities of glaucolide B in human cultured lymphocytes and in bone marrow cells from BALB/c mice. The mitotic index (MI) and chromosomal aberrations were analyzed in both of the above systems, whereas sister chromatid exchanges (SCE) and the proliferation index (PI) were determined only in vitro. In human cultured lymphocytes, glaucolide B concentrations greater than 15 µg/ml of culture medium completely inhibited cell growth. At 4 µg/ml and 8 µg/ml of culture medium, glaucolide B significantly increased the frequency of chromosomal aberrations in lymphocytes and was also cytotoxic at concentrations ³8 µg/ml; there was no increase in the frequency of SCE. Glaucolide B (160-640 mg/kg) did not significantly increase the frequency of chromosomal aberrations in mouse bone marrow cells nor did it affect cell division. Since glaucolide B showed no clastogenic action on mammalian cells in vivo but was cytotoxic and clastogenic in vitro, caution is needed in its medicinal use.
Highlights
Plants synthesize toxic chemicals in large amounts, primarily as a defense against bacterial, fungal, insect and other animal predators
The total frequency of chromosomal aberrations at glaucolide B concentrations of 4 and 8 μg/ml was significantly higher than the controls (P = 0.0387)
Compared with the negative control, glaucolide B significantly increased number of cells with chromosome aberrations only at the highest concentration tested (P = 0.0407) (Table I). This concentration significantly decreased the mitotic index compared to the controls (P = 0.0206)
Summary
Plants synthesize toxic chemicals in large amounts, primarily as a defense against bacterial, fungal, insect and other animal predators. The active compounds have been shown to be sesqui- and diterpenes (Gilbert et al, 1970). The sesquiterpene lactones (SL) from plants comprise a group of substances with a variety of biological effects. These compounds are terpenoids and are characteristic of the Asteraceae but may occur in other angiosperm plant families as well as in plants of the genus Hepatica; their principal structural characteristic is the presence of α,βunsaturated γ-lactone (Rodriguez et al, 1976). SL possess antibacterial, antifungal, antitumor, antiprotozoal, antihelminthic, schistosomicidal, cytotoxic and analgesic activities (Picman, 1986). Glaucolide B (Figure 1) is an SL that is active against the embryos and adults of Biomphalaria glabrata snails, causing approximately 70 and 90% mortality, respectively, within 24 h; this compound has an analgesic action in mice and shows strong antimicrobial activity against Bacillus cereus (Alarcon et al, 1990)
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