Paeoniflorin abrogates DSS-induced colitis via a TLR4-dependent pathway

Abstract

Paeonia lactiflora Pall is one of the most well-known herbs in China, Korea, and Japan for more than 1,200 years. Paeoniflorin, the major bioactive component of peony root, has recently been reported to have anticolitic activity. However, the underlying molecular mechanism is unclear. The present study was to explore the possible mechanism of paeoniflorin in attenuating dextran sulfate sodium (DSS)-induced colitis. Pre- and coadministration of paeoniflorin significantly reduced the severity of colitis and resulted in downregulation of several inflammatory parameters in the colon, including the activity of myeloperoxidase (MPO), the levels of TNF-α and IL-6, and the mRNA expression of proinflammatory mediators (MCP-1, Cox2, IFN-γ, TNF-α, IL-6, and IL-17). The decline in the activation of NF-κB p65, ERK, JNK, and p38 MAPK correlated with a decrease in mucosal Toll-like receptor 4 (TLR4) but not TLR2 or TLR5 expression. In accordance with the in vivo results, paeoniflorin downregulated TLR4 expression, blocked nuclear translocation of NF-κB p65, and reduced the production of IL-6 in LPS-stimulated mouse macrophage RAW264.7 cells. Transient transfection assay performed in LPS-stimulated human colon cancer HT-29 cells indicated that paeoniflorin inhibits NF-κB transcriptional activity in a dose-dependent manner. TLR4 knockdown and overexpression experiments demonstrated a requirement for TLR4 in paeoniflorin-mediated downregulation of inflammatory cytokines. Thus, for the first time, the present study indicates that paeoniflorin abrogates DSS-induced colitis via decreasing the expression of TLR4 and suppressing the activation of NF-κB and MAPK pathways.

Notoginsenoside R1 Attenuates Experimental Inflammatory Bowel Disease via Pregnane X Receptor Activation

“…The use of medicinal plants or their active components is becoming an increasingly attractive approach for the management of IBD (Shin et al, 2009;Zhang et al, 2014). In the present study, as a part of our ongoing screening program to evaluate the antiinflammatory potentials of natural compounds (Dou et al, 2013a;Zhang et al, 2014), we investigated the anti-inflammatory effects of R1 on DSS-or TNBS-induced colitis. To our knowledge, the present study is the first to demonstrate a beneficial effect of R1 on chemically induced IBD (UC-or CD-like).…”

The anti-inflammatory effect and potential mechanism of cardamonin in DSS-induced colitis

“…DSS colitis was induced in female C57-BL/6 mice, as described previously (6,27). Animals were randomly divided into the following groups (n ϭ 10 per group):…”

“…The tissue samples were then embedded in paraffin wax, stained with hematoxylin and eosin, and assessed under microscopy. Tissue damage was scored, as described previously (6,27).…”

“…MPO is an enzyme produced mainly by polymorphonuclear leukocytes, and its activity in the colon is linearly related to neutrophil infiltration (27). MPO activity levels were low in the colon of vehicle-treated mice and markedly increased in mice with DSS-induced colitis ( Table 1).…”

“…Despite optimal medical therapy, about one-third of patients with UC and two-thirds of those with Crohn's disease eventually require surgery at certain point during the course of the treatments (11). Therefore, new agents, especially those with limited side-effects and clear molecular mechanisms have been intensively investigated in recent years (26,27).…”