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We have investigated the anti-inflammatory effects of madecassic acid and madecassoside isolated from Centella asiatica (Umbelliferae) on lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Both madecassic acid and madecassoside inhibited the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and IL-6. However, madecassic acid more potently suppressed these inflammatory mediators than did madecassoside. Consistent with these observations, madecassic acid inhibited the LPS-induced expression of iNOS and COX-2 at the protein level and of iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6 at the mRNA level in RAW 264.7 macrophage cells, as determined by Western blotting and RT-PCR, respectively. Furthermore, madecassic acid suppressed the LPS-induced activation of nuclear factor-kappaB (NF-kappaB), and this was associated with the abrogation of inhibitory kappa B-alpha (IkappaB-alpha) degradation and with the subsequent blocking of p65 protein translocation to the nucleus. These results suggest that the anti-inflammatory properties of madecassic acid are caused by iNOS, COX-2, TNF-alpha, IL-1beta, and IL-6 inhibition via the downregulation of NF-kappaB activation in RAW 264.7 macrophage cells., (Georg Thieme Verlag KG Stuttgart-New York.)

To investigate the anti-inflammatory potential of sinapic acid as well as the underlying mechanism involved, we studied the inhibitory effect of sinapic acid on the production of pro-inflammatory mediators in vitro and then evaluated its in vivo anti-inflammatory effect. Sinapic acid inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E 2 (PGE 2), tumor necrosis factor (TNF)-alpha, and interleukin (IL)-1beta production in a dose-dependent manner. Consistent with these findings, sinapic acid inhibited LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygase (COX)-2 at the protein levels, and iNOS, COX-2, TNF-alpha, and IL-1beta mRNA expression in RAW 264.7 macrophages, as determined by Western blotting and reverse-transcribed polymerase chain reaction, respectively. Sinapic acid suppressed the LPS-induced activation of nuclear factor-kappaB (NF-kappaB), a transcription factor pivotal necessary for pro-inflammatory mediators, such as iNOS, COX-2, TNF-alpha, and IL-1beta. This effect was accompanied by a parallel reduction of the nuclear translocation of p65 and p50 NF-kappaB subunits, as well as IkappaB-alpha degradation and phosphorylation. The effects of sinapic acid on acute phase inflammation were investigated on serotonin- and carrageenan-induced paw edema and compared with indomethacin (10 mg/kg, p.o.) or ibuprofen (100 mg/kg, p.o.). Maximum inhibitions of 34.2 and 44.5% were observed at a concentration of 30 mg/kg for serotonin- and carrageenan-induced paw edema, respectively. These results suggest that the suppressions of the expressions of iNOS, COX-2, TNF-alpha, and IL-1beta via NF-kappaB inactivation are responsible for the anti-inflammatory effects of sinapic acid.