Inhibition of Prostaglandin E2 Production by Flavone and its Related Compounds

We have previously reported that among 12 major ingredients of Sairei-to, Scutellariae radix inhibited prostaglandin E 2 (PGE 2 ) production by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells more efficiently than other ingredients, and wogonin, a major flavonoid from Scutellariae radix, showed greater inhibitory activity and membrane permeability than baicalein and baicalin. Here the effects of six other flavonoids, with similar structures, on membrane permeability and PGE 2 production were investigated. 7-Methoxyflavone inhibited the LPS- stimulated PGE 2 production to the greatest extent, followed by flavone>wogonin (5,7-dihydroxy-8-methoxyflavone)>> 7,8- dimethoxyflavone>chrysin (5,7-dihydroxyflavone)> baicalein (5,6,7-trihydroxyflavone)>>chromone. 7-Methoxyflavone also showed the highest membrane permeability, followed by flavone>chrysin>7,8-dimethoxy-flavone>wogonin>baicalein. When PGE 2 inhibitory activity was expressed per molecule incorporated into the cells, wogonin produced the greatest inhibition, further substantiating its anti-inflammatory potency. Scutellariae radix is one of the major ingredients in Kampo medicines or traditional Chinese herbal medicines. Various analytical methods, such as high performance liquid chromatography (HPLC), thin layer chromatography, and mass spectrometry have been used to identify or quantify the marker components for quality control and standardization purposes for medicinal plants (1). These methods are useful to ensure their consistent pharmacological and biological activity and stability. Scutellariae radix, one of 12 major ingredients of Sairei-to, possesses a broad spectrum of biological activities (2-4) and contains baicalin, baicalein and wogonin as major flavonoids. However, the biological significance of these flavonoids is unclear. We have previously investigated the potency of baicalin, baicalein and wogonin in inhibiting lipopolysaccharide (LPS)-stimulated prostaglandin E 2 (PGE 2 ) production in conjunction with their membrane permeability assessed by HPLC, and found that wogonin and all the other ingredients failed to inhibit the expression of cyclooxygenase- 2 (COX-2) at both protein and mRNA levels (5). The metabolic pharmacokinetics of baicalin and baicalein has been reported (6, 7). Here seven related compounds were investigated for their inhibitory activity on PGE 2 production by LPS-stimulated mouse macrophage-like RAW264.7 cells, in relation to their membrane permeability. The compounds used in this study were chromone, flavone, 5,7-dihydroxyflavone (chrysin), 5,6,7- trihydroxyflavone (baicalein), 5,7-dihydroxy-8-methoxyflavone (wogonin), 7-methoxyflavone and 7,8-dimethoxyflavone (structures shown in Figure 1). Materials and Methods