Cytotoxic and apoptosis-inducing activities against human lung cancer cell lines of cassaine diterpenoids from the bark of Erythrophleum fordii.

A phytochemical investigation into the bark of Erythrophleum fordii yielded four new compounds, two new cassaine diterpenoids (erythrofordin T and U, 1 and 2) and two new cassaine diterpenoid amines (erythroformine A and B, 6 and 7), as well as nine known compounds. We report for the first time the isolation of erythrofordin V (3) from a natural source and that of the remaining eight known diterpenoids (4-5, 8-13) from E. fordii. All structures were elucidated using spectroscopic analysis. Cytotoxic activity of the isolated compounds (1-13) was examined in vitro against three non-small cell lung cancer cell lines (A549, NCI-H1975, and NCI-H1229) using the MTT assay. Cassaine diterpene amines (6-10, 12, 13) exhibited potent cytotoxic activity against all three cell lines with IC50 values between 0.4µM and 5.9µM. Erythroformine B (7) significantly induced apoptosis in all three cancer cells in a concentration-dependent manner.

Cytotoxic constituents from the seeds of Vietnamese Caesalpinia sappan.

CONTEXT: Caesalpinia sappan Linn. (Leguminosae) has been used in folk medicines for the treatment of many diseases. The heartwood of this plant contains various phenolic components with interesting biological applications; however, the chemical and biological potentials of the seed of this plant have not been fully explored. OBJECTIVE: This study identified the cytotoxic activity of compounds from the seeds of C. sappan. MATERIALS AND METHODS: The methanol extract of the seed of C. sappan was suspended in H2O and then partitioned with CH2Cl2, EtOAc, and n-BuOH, successively. Diterpenoid compounds were isolated from the CH2Cl2-soluble fraction by silica gel column chromatography methods using organic solvents. The compound structures were determined by detailed analysis of NMR and MS spectral data. Cytotoxic activity was measured using a modified MTT assay against HL-60, HeLa, MCF-7, and LLC cancer cells. The activation of caspase-3 enzyme and western blotting assay were performed to confirm inhibitory mechanism of active compound. RESULTS: Five cassane-type diterpenoids were isolated and identified as phanginin I (1), phaginin A (2), phanginin D (3), phanginin H (4), and phanginin J (5). Compounds 1-4 showed effective inhibition against HL-60 cells with the IC50 values of 16.4 ± 1.5, 19.2 ± 2.0, 11.7 ± 1.6, and 22.5 ± 5.1 µM. Compounds 1-3 exhibited cytotoxic activity against HeLa cells with the IC50 values of 28.1 ± 3.6, 37.2 ± 3.4, and 22.7 ± 2.8 µM. Treatment of HL-60 cell lines with various concentrations of 3 (0-30 µM) resulted in the growth inhibition and induction of apoptosis. CONCLUSION: These findings demonstrate that compound 3 (phanginin D) is one of the main active components of the seed of C. sappan activating caspases-3 which contribute to apoptotic cell death.

Inhibitory effect of schizandrin on passive cutaneous anaphylaxis reaction and scratching behaviors in mice.

To evaluate the antiallergic effect of the fruit of Schizandra chinensis Baill (Family Magnoliaceae), which inhibited the mouse passive cutaneous anaphylaxis (PCA) reaction in a preliminary experiment, its main constituent, schizandrin, was isolated and its antiallergic effect investigated. Schizandrin inhibited the PCA reaction induced by the IgE-antigen complex, the scratching behaviors induced by compound 48/80 and the serum IgE production induced by ovalbumin. Schizandrin also inhibited the in vitro degranulation of compound 48/80-induced rat peritoneal mast cells and IgE-induced RBL 2H3 cells. Schizandrin reduced the protein expressions of TNF-alpha and IL-4 in IgE-induced RBL 2H3 cells. These findings suggest that schizandrin can improve IgE-induced anaphylaxis and scratching behaviors.