No abstract

The hepatotoxin okadaic acid (OA) was incubated with nine human recombinant cytochrome P450s (1A1, 1A2, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5). Both CYP3A4 and CYP3A5 converted OA to a mixture of the same four metabolites, but incubation with CYP3A4 resulted in higher levels of conversion. Michaelis-Menten parameters, K m (73.4 μM) and V max (7.23 nmol of metabolites nmol -1 min -1 ) for CYP3A4 were calculated by analyzing double-reciprocal plots. LC-MS n analysis and chemical interconversion indicate that metabolites 2 and 3 are the 11S-hydroxy and 11R-hydroxy okadaic acid respectively, while metabolite 4 is 11-oxo okadaic acid. LC-MS n analysis of metabolite 1 shows a molecular ion which corresponds to an addition of 16 amu to OA, also suggesting hydroxylation, but the specific site has not been identified. The same four metabolites were produced upon incubation of okadaic acid with pooled human liver microsomes. This transformation could be completely inhibited with ketokonazole, and inhibitor of the CYP3A family of enzymes. The metabolites were determined to be only slightly less potent inhibitors of serine threonine protein phosphatase 2A (PP2A) when compared to OA. As PP2A is the principle molecular target for OA, these oxidative transformations may not effectively detoxify OA.

Spatholobus suberectus Dunn, belonging to the legume family (Fabaceae), has been used as a Traditional Chinese Medicine for the treatment of anemia, menoxenia and rheumatism. A limited number of studies report that various types of flavonoids are the main characteristic constituents of this herb. We have now found that S. suberectus contains about 2% phenolic components and characterized the major phenolic components as homogeneous B-type procyanidin conjugates using a liquid chromatography with diode-array detection-ESI mass spectrometry (LC-DAD/ESI-MS) method. This is the first report on occurrence of most B-type procyanidins in this herb. Moreover, the total phenolics extract was assayed for inhibitory activity on human neutrophil elastase and its IC 50 was found to be 1.33 μg/mL.

No abstract

As important members of the terpenes family, sesquiterpenes represent a group of natural compounds with diverse skeletal types. Among them, the eremophilane-type sesquiterpenes, widely present in several genera (such as Ligularia, Senecio, Cacalia) of Asteraceae, account for a small number of natural compounds and form differently from other sesquiterpenes because they challenged the isoprene rule of biosynthesis. Due to the unique structural features and various functional groups, these compounds possess a number of biological activities such as anti-tumor, anti-bacterial and anti-inflammatory, having received increasing interest in the recent years. This review summarizes the occurrence of eremophilane-type sesquiterpenes and research progresses on their biological activities since the 1990 s.