Fig. 3 Modulation by 2 and 2a of LPS-induced iNOS
expression in RAW 264.7 cells. Lysates were prepar-
ed from control or 24 h-LPS (1 mg/mL) stimulated
cells alone or in combination with increasing con-
centrations (30-60-120 mM) of liriodendrin and
syringaresinol. All lanes contained 50 mg of total
proteins. A representative immunoblot from three
separate experiments is shown.
Fig. 4 Modulation by 2 and 2a of LPS-induced COX-
2 expression in RAW 264.7 cells. Lysates were pre-
pared from control or 24 h-LPS (1 mg/mL) stimulated
cells alone or in combination with increasing con-
centrations (30-60-120 mM) of liriodendrin and
syringaresinol. All lanes contained 50 mg of total
proteins. A representative immunoblot from three
separate experiments is shown.
Liriodendrin was found to significantly increase hot-plate reac- by syringaresinol occurs mainly through the regulation of iNOS
tion time in mice. It is known that centrally acting analgesic and COX-2 gene expression. However, we cannot rule out the
drugs elevate the pain threshold of mice towards heat. In order possibility that syringaresinol directly interferes with iNOS and
to distinguish between the central and peripheral analgesic ac- PGE2 activity. Moreover, the development of hyperalgesic states
tion, the acetic acid-induced writhing response in mice was during inflammation is thought to be mediated by pro-inflam-
used to examine the effect. It was found that liriodendrin signifi- matory cytokines such as TNF-a, IL-1 and IL-6 [20]. Therefore,
cantly inhibited the acetic acid-induced writhing response in a we investigated whether syringaresinol and liriodendrin could
dose-dependent manner. The abdominal constriction is related possibly influence the formation of TNF-a in an in vitro model.
to the sensitization of nociceptive receptors to prostaglandins. It We demonstrated that liriodendrin and syringaresinol signifi-
is therefore possible that liriodendrin exerts an analgesic effect cantly inhibit TNF-a production in a concentration-dependent
probably by inhibiting the synthesis or action of prostaglandins.
manner and syringaresinol has higher activity than liriodendrin.
615
In many cases, it appears that the active moiety in many glyco- Based on these results, we concluded that oral administration of
sides existing in plant resources should be attributed to the agly- liriodendrin results in a potent anti-inflammatory and antinoci-
cone. This suggestion was supported by our previous results in- ceptive activity. In addition, the true active moiety of lirioden-
dicating that liriodendrin is transformed to the more cytotoxic drin could be syringaresinol producible from the glycoside in
syringaresinol by human intestinal bacteria [19]. Syringaresinol the living system rather than the gross structure.
is much less frequently found in Araliaceae plants than its glyco-
sides, suggesting that the former is more unstable than the latter.
This is presumed from the production of a variety of artifacts on References
acid hydrolysis of liriodendrin.
1
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It is well known that macrophages play a crucial role in both
non-specific and acquired immune responses, and macrophage
activation by LPS leads to a functionally diverse series of respon-
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was significantly blocked by syringaresinol. In addition to inhibi-
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tially inhibited PGE2 production and COX-2 gene expression in
LPS-treated RAW 264.7 macrophages. Therefore, these results
suggest that inhibition of LPS-induced NO and PGE2 production
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