Dietary Coleus forskohlii extract generates dose-related hepatotoxicity in mice

Coleus forskohlii root extract (CFE) represented by its bioactive constituent 'forskolin' is popularly used as a natural weight-lowering product, but the association of its use with liver-related risks is very limited. In the present study, the effect of standardized CFE with 10% forskolin on liver function of mice was examined. Mice were given 0-5% CFE in an AIN93G-based diet for 3-5 weeks. Food intake, body weights, relative organ weights and liver marker enzymes [aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP)] combined with histophatological analysis were assessed. CFE (0-0.5%) only had minimal effects on food intake and body weight whereas a significant difference was observed in mice receiving the highest dose (5% CFE). The extract 0.05-5% dose-dependently decreased visceral fat weight by between 16% and 63%, and a dose-dependent several folds increase was observed in liver weights and plasma AST, ALT and ALP activities with quick onset apparent after only 1 week of 0.5% CFE intake. The hepatic effect persisted throughout the 3-weeks course but was restored towards normalization within 1 week after withdrawal of treatment. Liver histology of mice fed 0.5% CFE for 3 weeks showed hepatocyte hypertrophy and fat deposition. In contrast, none of the hepatic responses measured were altered when mice were given a diet containing pure forskolin alone at the dose corresponding to its content in 0.5% CFE. The present study clearly indicated that forskolin was not involved in the CFE-induced hepatotoxicity and was caused by other unidentified constituents in CFE which warrants further studies.