Seasonal influence and cytotoxicity of extracts, fractions and major compounds from Allamanda schottii

The aim of this research was to evaluate the fractions obtained from the leaf, stem and roots of Allamanda schottii Pohl, Apocynaceae, responsible for the cytotoxicity, using several cell lines. Cytotoxicity was correlated with the season the part of the plant, and the major compounds were assessed. The ethanol extracts of leaves, stems and roots obtained at different seasons were evaluated in the human erythromyeloblastoid leukemia cell line (K562). Subsequently the ethanol extracts and dichloromethane fractions collected in winter were evaluated in mouse fibroblast cell line (Mus musculus) (L929), cervix adenocarcinoma (HeLa), human pre-B leukemia (Nalm6), as well as K562 cell line. The compounds plumericin, plumieride and ursolic acid isolated from ethanol extracts of the stems were evaluated in the same cell lines, as well as on breast adenocarcinoma cell line (MCF-7), and Mus musculus skin melanoma cell line (B16F10). The chromatographic profiles of the dichloromethane fractions were obtained by high performance liquid chromatography. The results revealed that the season during which A. schottii was collected, and the part of the plant analyzed, influence the cytotoxicity on the K562 cells tested. On the other hand the dichloromethane fractions, mainly from the stems and roots, are responsible for the cytoxicity on the cells tested. These results may be associated with the seasonal variation of plumericin in these parts of the plant. This information is in accordance with the HPLC analysis. The results clearly show the potential for the phytotherapeutic use of this species, and suggest that the cytotoxic activity observed may be due to the presence of plumericin, or to minor compounds not yet identified. The seasonal influence on the production of secondary metabolites was verified.

The plants of the genus Phyllanthus as a potential source of new drugs

The plants of the genus Phyllanthus (Euphorbiaceae) comprise about 550 to 750 species which are widely distributed in most tropical and subtropical countries. About 200 species are believed to occur in the Americas, mainly in the Caribbean and Brazil. The plants of the genus Phyllanthus have long been used in folk medicine to treat, among others, kidney and urinary bladder disorders, intestinal infections, diabetes and hepatitis B. In recent years, substantial progress in chemical and pharmacological studies, and a few clinical studies of some Phyllanthus species, were made. This review discusses the current knowledge gained by the in vitro and in vivo pharmacological and biochemical studies performed with the extracts and the main active constituents isolated from different species of plants of the genus Phyllanthus. Data available in the literature strongly support the idea that the extract and some constituents isolated from these plants, including flavanoids, tannins, alkaloids, coumarins, lignans and terpenes, account for their reported antinociceptive, anti-inflammatory, antiviral, antispasmodic and antiallergic properties. In addition, some of these compounds were found to interact with most key enzymes, such as aldose reductase, angiotensin converting enzyme, mitochondrial ATPase, both cyclo- and lipooxygenases, phospholipase A2, tyrosine kinase, reverse transcriptase, and phosphodiesterases. The complex mechanism of action of such compounds could explain, at least in part, the wide therapeutic use of the plants of the genus Phyllanthus in folk medicine. Thus, the plants of the genus Phyllanthus present potential therapeutic interest as a source of new drugs.

Natural bradykinin antagonists

Bradykinin (BK) a nonapeptide generated in plasma during tissue injury, is involved in many physiological and pathological states. Kinin actions are mediated by specific membrane receptors and involve a complex signal transducer and also second messager mechanisms. Due to its inequivocal relevance, an intensive effort has been focused in recent years to develop selective and competitive BK antagonists. Thus, the development of a new series of peptide BK antagonists has made an important contribution to the understanding of the pharmacological, physiological and pathophysiological role of BK, and this is certain to provide a firm basis for developing new drugs to relieve pain and inflammation. However, BK antagonists derived from peptide origin reported to date have limited clinical use due to their poor oral absortion and short duration of effect. Thus, considerable effort has also been made in developing stable nonpeptide BK antagonists. Up to now, most nonpeptide compounds reported to exhibit BK antagonistic activity have been derived from plants, including many flavonoids, terpenes, and also synthetic substances with various molecular structures. Amongst them, the pregnane glycoside compounds isolated from the plant Mandevilla velutina are the most promising. These compounds are effective in antognizing BK responses in a variety of preparations, and they also exhibit potent and long-lasting analgesic and anti-inflammatory activities. The exact mechanism underlying their action however, is not yet completely understood.