No abstract

These findings indicate that β-sitosterol ameliorates HFD-induced colitis by inhibiting the binding of LPS to toll-like receptor 4 in the NF-κB pathway.

Ursolic acid, which was isolated from an ethanol extract of Cornus officinalis seed, potently inhibited nuclear factor κ light-chain enhancer of activated B cells (NF-κB) activation in lipopolysaccharide (LPS)-stimulated peritoneal macrophages. Therefore, we investigated the anti-inflammatory mechanism of ursolic acid in LPS-stimulated macrophages and colitic mice. Ursolic acid inhibited phosphorylation of interleukin 1 receptor-associated kinase (IRAK)1, TAK1, inhibitor of nuclear factor κB kinase subunit β (IKKβ), and IκBα as well as activation of NF-κB and MAPKs in LPS-stimulated macrophages. Ursolic acid suppressed LPS-stimulated interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, and inducible NO synthetase (iNOS) expression as well as PGE2 and NO levels. Ursolic acid not only inhibited the Alexa Fluor 488-conjugated LPS-mediated shift of macrophages but also reduced the intensity of fluorescent LPS bound to the macrophages transiently transfected with or without MyD88 siRNA. However, ursolic acid did not suppress NF-κB activation in peptidoglycan-stimulated macrophages. Oral administration of ursolic acid significantly inhibited 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colon shortening and myeloperoxidase (MPO) activity in mice. Ursolic acid also suppressed TNBS-induced COX-2 and iNOS expression as well as NF-κB activation in colon tissues. Ursolic acid (20 mg/kg) also inhibited TNBS-induced IL-1β, IL-6, TNF-α by 93, 86, and 85%, respectively (p < 0.05). However, ursolic acid reversed TNBS-mediated downregulation of IL-10 expression to 79% of the normal control group (p < 0.05). On the basis of these findings, ursolic acid may ameliorate colitis by regulating NF-κB and MAPK signaling pathways via the inhibition of LPS binding to TLR4 on immune cells.

Ginseng (the root of Panax ginseng C.A. Meyer, family Araliaceae), which contains protopanaxadiol ginsenoside Rb1 and protopanaxatriol ginsenoside Re as main constituents, is frequently used to treat cancer, inflammation, and stress. In the preliminary study, protopanaxatriol ginsenoside Re inhibited NF-κB activation in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. Therefore, we investigated its anti-inflammatory effect in peptidoglycan (PGN)-, LPS-, or tumor necrosis factor-α (TNF-α)-stimulated peritoneal macrophages and, in addition, in LPS-induced systemic inflammation and 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. Ginsenoside Re inhibited IKK-β phosphorylation and NF-κB activation, as well as the expression of proinflammatory cytokines, TNF-α and IL-1β, in LPS-stimulated peritoneal macrophages, but it did not inhibit them in TNF-α- or PG-stimulated peritoneal macrophages. Ginsenoside Re also inhibited IRAK-1 phosphorylation induced by LPS, as well as IRAK-1 and IRAK-4 degradations in LPS-stimulated peritoneal macrophages. Ginsenoside Re inhibited the binding of Alexa Fluor 488-conjugated LPS to TLR4 on peritoneal macrophages. Furthermore, ginsenoside Re inhibited the binding of LPS to TLR4 on peritoneal macrophages transiently transfected with MyD88 siRNAs. Orally administered ginsenoside Re significantly inhibited the expression of IL-1β and TNF-α on LPS-induced systemic inflammation and TNBS-induced colitis in mice. Ginsenoside Re inhibited colon shortening and myeloperoxidase activity in TNBS-treated mice. Ginsenoside Re reversed the reduced expression of tight-junction-associated proteins ZO-1, claudin-1, and occludin. Ginsenoside Re (20 mg/kg) inhibited the activation of NF-κB in TNBS-treated mice. On the basis of these findings, ginsenoside Re may ameliorate inflammation by inhibiting the binding of LPS to TLR4 on macrophages.

Aim: We isolated Lactobacillus brevis G-101 from kimchi lactic acid bacteria (LAB) strains, which induced IL-10 expression in lipopolysaccharide (LPS)-stimulated peritoneal macrophages. To evaluate the inflammatory effect of G-101, we examined its inhibitory effect in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitic mice. Materials and Results: The colitic mice were prepared by intrarectal injection of TNBS. We measured intestinal mucosal cytokines by enzyme-linked immunosorbent assay; activation of transcription factors, by immunoblotting; and macrophage polarization markers, by real-time polymerase chain reaction. Of 200 LAB strains tested, Lact. brevis G-101 showed most potent activity for induction of IL-10 expression in LPS-stimulated peritoneal macrophages. However, it significantly inhibited the expression of TNF-a, IL-1b and IL-6 and the phosphorylation of IRAK1 and AKT, and activated NF-jB and MAPKs. Treatment with TNBS caused colon shortening; increased myeloperoxidase activity; and increased IL-1b, IL-6 and TNF-a expression in mice. Oral administration of Lact. brevis G-101 significantly inhibited these activities. Lactobacillus brevis G-101 inhibited TNBS-induced IRAK-1 phosphorylation and NF-jB activation, as well as the expression of COX-2 and iNOS. Lactobacillus brevis G-101 inhibited the expression of M1 macrophage markers, but increased the expression of M2 macrophages in the colons of TNBS-treated mice. Conclusions: Lactobacillus brevis G-101 may improve colitis by inhibiting the IRAK1/NF-jB, MAPK and AKT pathways and by polarizing M1 macrophages to M2-like macrophages. Significance and Impact of the Study: These results suggest that IL-10 expression-inducing LAB can ameliorate colitis by inhibiting NF-jB activation and macrophage polarization.