Silibinin Inhibits LPS-Induced Macrophage Activation by Blocking p38 MAPK in RAW 264.7 Cells

Abstract

We demonstrate herein that silibinin, a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), inhibits LPS-induced activation of macrophages and production of nitric oxide (NO) in RAW 264.7 cells. Western blot analysis showed silibinin inhibits iNOS gene expression. RT-PCR showed that silibinin inhibits iNOS, TNF-α, and IL1β. We also showed that silibinin strongly inhibits p38 MAPK phosphorylation, whereas the ERK1/2 and JNK pathways are not inhibited. The p38 MAPK inhibitor abrogated the LPS-induced nitrite production, whereas the MEK-1 inhibitor did not affect the nitrite production. A molecular modeling study proposed a binding pose for silibinin targeting the ATP binding site of p38 MAPK (1OUK). Collectively, this series of experiments indicates that silibinin inhibits macrophage activation by blocking p38 MAPK signaling.

Anti-Inflammatory Effects of Chloranthalactone B in LPS-Stimulated RAW264.7 Cells

“…These results suggest that phosphorylation of p38 MAPK is involved in the inhibitory effects of CTB on LPS-induced inflammatory gene expression. Next, we moved forward to test the activation of phosphorylations of MKK3/6, which are two closely related kinases that phosphorylate p38 at its Thr-Gly-Tyr site [47]. As shown in Figure 5D, the increased phosphorylation of MKK3/6 induced by LPS was suppressed by CTB in a dose-dependent manner, but that this did not affect the total amount of MKK3/6.…”

Silybin reduces obliterated retinal capillaries in experimental diabetic retinopathy in rats

“…Recent studies also demonstrated that silybin possessed anti-inflammatory properties (Al-Anati et al, 2009;Chittezhath et al, 2008;Giorgi et al, 2012;Gu et al, 2007;Kim et al, 2012;Prabu and Muthumani, 2012;Salamone et al, 2012;Youn et al, 2013). Therefore, silybin might be a suitable protective agent for early diabetic retinopathy.…”

Anti-allergic effect of α-cubebenoate isolated from Schisandra chinensis using in vivo and in vitro experiments

“…Specific primers for TGF-1 (sense 5′-TTG CTT CAG CTC CAC AGA GA-3′, antisense 5′-TGG TTG TAG AGG GCA AGG AC-3′), IL-4 (sense 5′-ACG GAG ATG GAT GTG CCA AAC-3′, antisense 5′-AGC ACC TTG GAA GCC CTA CAG A), and IL-13 (sense 5′-CGG CAG CAT GGT ATG GAG TG-3′, antisense 5′-ATT GCA ATT GGA GAT GTT GGT CAG-3′) were used to amplify gene fragments. PCR was performed over 27 cycles of denaturation at 95 o C for 30 s, annealing at 52 o C for 30 s, and elongation at 72 o C for 30 s in an Eppendorf Mastcycler PCR machine (Hamburg, Germany)(Youn et al, 2013). Specific primers for GAPDH (sense 5′-TTC ACC ACC ATG GAG AAG GC-3′, antisense 5′-GGC ATG GAC TGT GGT CAT GA-3′) were used and annealing was undertaken at 60°C.…”