Assessment of the cytotoxic potential of an aqueous-ethanolic extract from Thalassia testudinum angiosperm marine grown in the Caribbean Sea.

OBJECTIVES: Reported antioxidant, anti-inflammatory and neuroprotective properties for one aqueous-ethanolic extract from Thalassia testudinum which grows in the Caribbean Sea compelled us to explore about extract cytotoxic effects. METHODS: Cell viability was assayed on tumour (HepG2, PC12, Caco-2 and 4T1) and non-tumour (VERO, 3T3, CHO, MCDK and BHK2) cell lines. The extract effects upon primary cultures of rat and human hepatocytes and human lymphocytes were assayed. KEY FINDINGS: The extract exhibited cytotoxicity against cancer cells compared to normal cells, and the IC50 values were 102 µg/ml for HepG2, 135 µg/ml for PC12, 165 µg/ml for Caco-2 and 129 µg/ml for 4T1 cells after 48 h, whereas IC50 could not be calculated for normal cells. Additional data from a high-content screening multiparametric assay indicated that after 24-h exposure, the extract (up to 100 µg/ml) induced death in HepG2 cells through oxidative stress-associated mechanism, DNA damage and hypercalcaemia. Comet assay corroborated extract-induced DNA damage. CONCLUSIONS: Thalassia testudinum extract is more cytotoxic and produced more DNA damage on human hepatoma cells than to other non-tumour cells. A possible mechanism is suggested for extract-induced cytotoxicity based on oxidative stress, nuclear damage and hypercalcaemia in HepG2 cells. T. testudinum may be a source for antitumour agents.

In vitro modulation of the cytochrome P450 and ABCB1/P-glycoprotein activities of the aqueous extract of Allophylus cominia (L) Sw. leaves.

BACKGROUND: The aqueous extract of the Allophylus cominia (L) Sw (Sapindaceae) leaves has shown anti-diabetic, anti-obesity and anti-inflammatory properties. In the Caribbean region, it is typically used for the treatment of type-2 diabetes. METHODS: Considering the herb-drug interaction, the aim of this study was to evaluate the potential effects of the A. cominia extract on the cytochrome P450 (CYP) (rat hepatocyte model) and P-glycoprotein (P-gp) (4T1 cell line) systems. RESULTS: The extract did not decrease the cell viability after being assayed by the MTT test at up to 1500 µg/mL for 72 h. The exposure of the cultured rat hepatocytes to the product (up to 250 µg/mL) for 48 h increased the activities of CYP-1A2, 2C9, and 2E1 by 1.46-, 1.60-, and 1.51-fold, respectively, compared with the controls. The activities of CYP-2B6, 2D6, and 3A4 were not significantly altered, whereas the activity of P-gp decreased by 2- and 4-fold. In addition, the extracts at 100 and 200 µg/mL significantly increased doxorubicin cytotoxicity in these cells 24 h after treatment. CONCLUSIONS: The findings indicate that the A. cominia extract modulates the CYP and P-gp systems increasing sensitivity to doxorubicin. Further studies are necessary to evaluate the potential herb-drug interaction or chemosensitive properties.

Inhibition of human P450 enzymes by natural extracts used in traditional medicine.

Different medicinal plants are widely used in Cuba and Mexico to treat several disorders. This paper reports in vitro inhibitory effects on the P450 system of herbal products commonly used by people in Cuba and Mexico in traditional medicine for decades. Experiments were conducted in human liver microsomes. The catalytic activities of CYP1A1/2, 2D6, and 3A4 were measured using specific probe substrates. The Heliopsis longipes extract exhibited a concentration-dependent inhibition of the three enzymes, and similar effects were produced by affinin (an alkamide isolated from the H. longipes extract) and two catalytically reduced alkamides. Mangifera indica L. and Thalassia testudinum extracts, two natural polyphenol-rich extracts, diminished CYP1A1/2 and 3A4 activities, but not the CYP2D6 activity. These results suggest that these herbs inhibit the major human P450 enzymes involved in drug metabolism and could induce potential herbal-drug interactions.