Early and late stage markers in hepatotoxicity of chaparral and ma‐huang

Among the most serious adverse effects for herbal medicines is the potential liver injury due to a central role of liver on metabolism of foreign substances Recently, several reports have shown about hepatotoxicity of chaparral( Larrea tridentata ) and ma‐huang( Ephedra ) used as traditional medicines. However, relatively little studies have been attempted on the development of biomarkers and assays for hepatotoxicity assessment of herbal medicines, particularly for detecting the early stage of hepatotoxicity. In this study, early cellular changes were monitored to assess hepatotoxicity of chaparral and ma‐hung. Human hepatoma HepG2 cells were incubated with various concentrations of aqueous ethanolic(70%) extracts of chaparral and ma‐huang. Hepatotoxicity of these herbal medicines was compared with that of acetaminophen and galactosamine, well‐known hepatotoxins. The markers to detect early and late stage hepatotoxicity include Fas, GSH, IL‐8, cytosolic Ca 2+ , ATP, cytochrome c, caspase‐8, steatosis, cholestasis, caspase‐3, MTT, and LDH. Chaparral, ma‐huang, acetaminophen and galactosamine showed hepatotoxicity in various assays. The early stage markers were observed at lower concentration than that needed for late stage events. These results indicate that herbal medicines such as chaparral and ma‐huang exert in vitro hepatotoxicity and may cause human liver injury. This study further suggests that assays using early stage markers as well as late stage markers are necessary to assess hepatotoxic potential of herbal medicines.