Biol. Pharm. Bull. 28(3) 455—460 (2005)

known as “Kwandong Hwa” in Korea and China, have long been used in traditional Oriental medicine for the treatment of bronchitis and asthma. However, only a few pharmacological actions have been demonstrated in vitro and in animals so far. T. farfara was reported to inhibit platelet aggregation by interfering with the binding of platelet activating factor to platelet membranes. In an animal study, it was shown to exhibit cardiovascular-respiratory stimulation. Tussilagone, (7R,14R)-14-acetoxy-7-[(2 E)-3 -methylpent2 -enoyloxy]-oplopanone, was found to be the active principle exhibiting the pressor effect in animals. More recently, T. farfara has been reported to inhibit arachidonic acid metabolism. Arachidonic acid is known to serve as a substrate for the generation of a variety of inflammatory mediators including prostaglandins, thromboxanes, leukotrienes, and reactive oxygen radicals. Thus, the inhibition of arachidonic acid metabolism by T. farfara may be one of the mechanisms by which it exerts antiinflammatory action. T. farfara has also been reported to inhibit nitric oxide (NO) synthesis in lipopolysaccharide-stimulated macrophages. Overproduction of NO is also strongly implicated in the pathophysiology of inflammatory conditions, and thus, the inhibition of NO production by T. farfara may also contribute to its antiinflammatory action. These findings may provide a basis for the traditional application of T. farfara to treat inflammatory conditions including asthma. Inflammation has also been widely recognized as a crucial mediator in the etiology of central nervous system (CNS) disorders. The expression of inflammatory mediators including cyclooxygenase enzymes and their products is shown to be increased in many acute and chronic neurodegenerative diseases, and several of these factors are found to contribute directly to neuronal injury. Moreover, excess NO has been viewed as a major agent of neuropathology, by directly or indirectly promoting oxidative and nitrosative stresses. Therefore, antiinflammatory agents and/or inhibitors of NO production are considered to be potentially beneficial for the managements of CNS disorders such as stroke and Alzheimer’s disease (AD). In the present study, we attempted to characterize pharmacological actions of T. farfara in the CNS using primary cultured rat cortical cells. According to our preliminary data, the hexane-soluble fraction of T. farfara exhibited cytotoxicity in cortical cells. In contrast, the ethyl acetate (EA)-soluble fraction was not toxic and exhibited antioxidant activity in vitro. Therefore, our study focused on the effects of the EA fraction. Based on the fact that T. farfara inhibits arachidonic acid metabolism, we first examined its effect on the neuronal damage induced by arachidonic acid. For further characterization, the effects on the neuronal damage induced by spermine NONOate (a stable NO generator), Ab, glutamate or N-methyl-D-aspartic acid (NMDA), or oxidative stress were also evaluated. In addition, its antioxidant properties were assessed in this study by cell-free bioassays.