Reactive oxygen species (ROS) act as subcellular messengers in such complex cellular processes as mitogenic signal transduction, gene expression, and regulation of cell proliferation.1) Excessive production of ROS may, however, cause oxidative stress, loss of cell function, and ultimately apoptosis or necrosis.2) Fortunately, cells possess antioxidant molecules which can neutralize ROS before they induce damage on vital components. However, oxidative stress occurs when antioxidant systems are overwhelmed by ROS. Oxidative stress is considered to play a prominent role in the causation of many diseases including aging, cardiovascular disease, cancer and liver injury. 3,4) tert-Butylhydroperoxide (t-BHP) is an organic hydroperoxidant that can be metabolized to free radical intermediates, which can subsequently initiate lipid peroxidation, affect cell integrity, and form covalent bonds with cellular molecules resulting in cell injury. 5) t-BHP causes leakage of lactate dehydrogenase (LDH) and formation of malondialdehyde (MDA) in hepatocytes, 6) and also mediates DNA base damage in mammalian cells. 7) These phenomena are similar to the oxidative stress occurring in the cell and/or tissue.Because of its unique metabolism and relationship to the gastrointestinal tract, the liver is an important target of the toxicity of drugs, xenobiotics, and oxidative stress. 8) Reactive oxygen species derived from chemicals or drugs exposed to liver cells seem to mediate liver injury, although the mechanisms of free radical toxicity are not well understood.
9)Therefore, primary importance is to understand the role of antioxidants which can reduce the oxidative stress induced by reactive intermediates from various chemicals and drugs. We have investigated hepatoprotective drugs, based on the measurement of cytotoxicity of t-BHP against human-liver-derived HepG2 cells. HepG2 cells have been suggested to be a useful in vitro model for investigation of the metabolism and toxicity of drugs compared with animal cells, since HepG2 cells retain many of the specialized functions which are characteristics of normal human hepatocytes, including the synthesis and secretion of plasma proteins.
10)Kaempferia pandurata ROXB. is a perennial herb of the family Zingiberaceae cultivated in some tropical countries, including Thailand and Indonesia. Its rhizome has been used as a food ingredient, an aphrodisiac, and a folk medicine for the treatment of colic disorder, fungal infections, dry cough, rheumatism, and muscular pains.11,12) Panduratin A (Fig. 1A) is a chalcone derivative isolated from K. pandurata. It was recently reported that panduratin A possessed significant topical anti-inflammatory activity in murine macrophages, 12) and in the TPA-induced ear edema in rats.
13)The objective of the current study was to examine the ability of panduratin A to protect hepatocytic injury induced by t-BHP and to characterize the mechanisms involved. For this purpose, we have studied the cell viability, lipid peroxidation, glutathione (GSH) level, and ROS le...