OBJECTIVES: This study aimed to determine whether Coleus forskohlii extract (CFE) influences the anticoagulant action of warfarin in mice in vivo and its relationship with hepatic cytochrome P450 (CYP). METHODS: Mice were fed various doses of CFE standardised with 10% forskolin in a normal diet for one week, or in protein diets containing 7% and 20% casein (low and normal) for four weeks. They were then administered with warfarin by gavage on the last two days of the treatment regimen, and blood coagulation parameters, as well as hepatic CYP, were analysed at 18 h after the last dose. Direct interaction between CFE and forskolin with CYP2C was evaluated in vitro. KEY FINDINGS: CFE dose dependently increased hepatic total CYP content and S-warfarin 7-hydroxylase activity at a dietary level of ≥0.05%. Warfarin-induced anticoagulation was attenuated by CFE in parallel with CYP induction. The findings were similar in mice fed diets containing CFE and different ratios of protein. CFE directly inhibited CYP2C activity in mouse and human liver microsomes in vitro, whereas forskolin was only slightly inhibitory. CONCLUSIONS: CFE attenuates the anticoagulant action of warfarin by inducing hepatic CYP2C; thus, caution is required with the combination of warfarin and dietary supplements containing CFE.
OBJECTIVES: This study aimed to determine whether Coleus forskohlii extract (CFE) influences the anticoagulant action of warfarin in mice in vivo and its relationship with hepatic cytochrome P450 (CYP). METHODS:Mice were fed various doses of CFE standardised with 10% forskolin in a normal diet for one week, or in protein diets containing 7% and 20% casein (low and normal) for four weeks. They were then administered with warfarin by gavage on the last two days of the treatment regimen, and blood coagulation parameters, as well as hepatic CYP, were analysed at 18 h after the last dose. Direct interaction between CFE and forskolin with CYP2C was evaluated in vitro. KEY FINDINGS: CFE dose dependently increased hepatic total CYP content and S-warfarin 7-hydroxylase activity at a dietary level of ≥0.05%. Warfarin-induced anticoagulation was attenuated by CFE in parallel with CYP induction. The findings were similar in mice fed diets containing CFE and different ratios of protein. CFE directly inhibited CYP2C activity in mouse and human liver microsomes in vitro, whereas forskolin was only slightly inhibitory. CONCLUSIONS: CFE attenuates the anticoagulant action of warfarin by inducing hepatic CYP2C; thus, caution is required with the combination of warfarin and dietary supplements containing CFE.
Authors: Luigi Barrea; Barbara Altieri; Barbara Polese; Barbara De Conno; Giovanna Muscogiuri; Annamaria Colao; Silvia Savastano Journal: Int J Obes Suppl Date: 2019-04-12
Authors: Pedro Paulo Barros; Gisele Mara Silva Gonçalves; Gustavo Henrique da Silva; Ana Laura Masquetti Fava Journal: Acta Cir Bras Date: 2019-08-19 Impact factor: 1.388