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1 Buddlejasaponin IV isolated from Pleurospermum kamtschatidum is an anti-inflammatory compound that inhibits NO, PGE 2 and TNF-a production. Here, we studied the mode of action of this compound. 2 Buddlejasaponin IV (2.5-10 mM) reduced lipopolysaccaride (LPS (1 mg ml À1 ))-induced levels of iNOS and COX-2 at the protein levels, and iNOS, COX-2, TNF-a, interleukin (IL)-1b and IL-6 mRNA expression in RAW 264.7 macrophages in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. 3 Buddlejasaponin IV inhibited the LPS-induced activation of nuclear factor-kB (NF-kB), a transcription factor necessary for proinflammatory mediators, iNOS, COX-2, TNF-a, IL-1b and IL-6 expression. This effect was accompanied by a parallel reduction in IkB-a degradation and phosphorylation, and by the nuclear translocation of the NF-kB p65 subunit. 4 The effects of buddlejasaponin IV on acute phase inflammation were studied on serotonin-and carrageenan-induced paw edema. The antiedematous effect of buddlejasaponin IV was compared with 10 mg kg À1 of indomethacin p.o. Maximum inhibitions of 26 and 41% were noted at a dose of 20 mg kg À1 for serotonin-and carrageenan-induced paw edema, respectively. 5 The analgesic effect of buddlejasaponin IV was evaluated using acetic acid-induced writhing and hot-plate tests. Buddlejasaponin IV (10 and 20 mg kg À1 , p.o.) was found to have a marked analgesic effect in both models. 6 These results suggest that the inhibitions of the expressions of iNOS, COX-2, TNF-a, IL-1b and IL-6 by blocking NF-kB activation, are responsible for the anti-inflammatory effects of buddlejasaponin IV isolated from P. kamtschatidum.

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We isolated a new saponin named codonoposide (1) from the roots of Codonopsis lanceolata (Campanulaceae) and characterized it as 3-O-[beta-D-xylopyranosyl(1-3)-beta-D-glucuronopyranosyl]-3beta,16alpha-dihydroxyolean-28-oic acid 28-O-[beta-D-xylopyranosyl (1-3)-alpha-L-rhamnopyranosyl (1-2)-alpha-L-arabinopyranosyl] ester by chemical, physicochemical, and 2DNMR techniques. Complete hydrolysis of 1 produced a sapogenin (1a), and the partial hydrolysis and further isolation afforded two prosapogenins (1b, 1c). The structures of 1a, 1b, and 1c were found to be 3beta,16alpha-dihydroxyolean-28-oic acid (echinocystic acid, 1a), 3-O-beta-D-glucuronopyranoside of 1a, and 3-O-beta-D-xylopyranosyl (1-3)-beta-D-glucuronopyranoside of 1a, respectively, on the basis of spectroscopic data. On MTT assay, 1a showed marginal cytotoxic activity whereas 1b exhibited more cytotoxicity than 1a. However, the bisdesmosylsaponin 1 exhibited no cytotoxicity (IC(50)>0.3 mM against tested cell lines). This result indicated that glycoside linkage of glucuronic acid at C-3 enhances the cytotoxicity of sapogenin (1a), and additive glycosylation of xylose to 1b strongly enhances the cytotoxicity of 3-O-monosaccharides (1b). Therefore, true forms of codonoposide for the cytotoxicity must be sapogenins or prosapogenins.

The root of Morinda officinalis (Rubiaceae) is used to treat rheumatoid arthritis and impotence in the traditional Oriental medicine. To identify the antinociceptive anti-inflammatory components of this crude drug, we adopted an activity-directed fractionation approach. The active fraction of the BuOH extract of M. officinalis root was subjected to silica gel and ODS column chromatography to yield two diterpenes, compounds 1 and 2 and these were identified as monotropein and deacetylasperulosidic acid, respectively. The iridoid glycoside, monotropein, was tested for its anti-inflammatory antinociceptive effects using hot plate-and writhing antinociceptive assays and by using carrageenan-induced anti-inflammatory assays in mice and rats. Pretreatment with monotropein (at 20, 30 mg/kg/d, p.o.) significantly reduced stretching episodes and prolonged action time in mice. It also significantly reduced acute paw edema by carrageenan in rats. These results indicate that monotropein contributes to the antinociceptive and anti-inflammatory action of Morinda officinalis root.

In the present study, syringin, isolated by activity-guided fractionation of the ethyl acetate (EtOAc) extracts of the stem bark of Magnolia sieboldii, and sinapyl alcohol, the hydrolysate of syringin, were evaluated for anti-inflammatory and antinociceptive activities. Sinapyl alcohol (20, 30 mg/kg/day, p. o.) inhibited increased vascular permeability by acetic acid in mice and reduced acute paw edema by carrageenan in rats more so than syringin. When analgesic activity was measured using the acetic acid-induced writhing test and the hot plate test, sinapyl alcohol was much more potent than syringin in a mouse model. In addition, sinapyl alcohol more potently inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), and tumor necrosis factor (TNF)-alpha production by macrophages than syringin. Consistent with these observations, the expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 was reduced by sinapyl alcohol in a concentration-dependent manner. These results suggest that the anti-inflammatory and antinociceptive effects of syringin after oral administration may be attributed to its in vivo transformation to sinapyl alcohol.