The Possible Anti‐Inflammatory Effect of Dehydrocostus Lactone on DSS‐Induced Colitis in Mice

Abstract

Background. Dehydrocostus lactone (DL), one of the main active constituents in Aucklandia lappa Decne. (Muxiang), reported to have anti-inflammatory, antiulcer, and immunomodulatory properties. However, the effect of DL on ulcerative colitis (UC) has not been reported. To analyze the anti-inflammatory potential role of DL in UC, we provide a mechanism for the pharmacological action of DL. Methods. The experimental model of UC was induced by using oral administration of 2% dextran sulfate sodium (DSS) with drinking water in BALB/c mice. Mesalazine (Mes, 0.52 g/kg/d), DL-high doses (DL-H, 20 mg/kg/d), DL-middle doses (DL-M, 15 mg/kg/d), DL-low doses (DL-L, 10 mg/kg/d) were gavaged once a day from day 4 to day 17. Disease activity index (DAI) was calculated daily. On day 18, mice were rapidly dissected and the colorectal tissues were used to detect the levels of UC-related inflammatory cytokines (TNF-α, IL-1β, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), and colorectal mucosal barrier-related regulatory factors (MUC2, XBP1s, and α-defensins) by ELISA or qRT-PCR. Results. DL reduced the colorectal inflammation histological assessment, decreased UC-related inflammatory cytokines (TNF-α, IL-1β, MCP-1, MPO, SOD, IL-6, IL-17, and IL-23), downregulated IL-6/STAT3 inflammatory signaling pathway (iNOS, COX2, IL-6, GP130, L-17, and IL-23), repaired the key colorectal mucosal barrier protein-MUC2, and inhibited the downstream pathway (XBP1s and α-defensin). Conclusions. DL possessed the potential of anti-inflammatory effect to treated colitis. The protective mechanism of DL may involve in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling.

Targeting IL‐10, ZO‐1 gene expression and IL‐6/STAT‐3 trans‐signaling by a combination of atorvastatin and mesalazine to enhance anti‐inflammatory effects and attenuates progression of oxazolone‐induced colitis

“…In the current study, there was a significant activation of IL‐6/STAT‐3 signaling and treatment with mesalazine significantly decreases IL‐6 and its downstream target STAT‐3 molecule level in colon tissues and these results are in agreement with [47,48]. Also, atorvastatin strongly downregulates IL‐6/STAT‐3 signaling and these results are in the same line of other reports [49,50].…”

Back to the Roots—An Overview of the Chemical Composition and Bioactivity of Selected Root-Essential Oils

“…Zhou et al were the first to report the anti-inflammatory potential ofDEH to treat ulcerative colitis in mice. Accordingly, the protective mechanism of DEH may be involved in reducing inflammation and improving colorectal barrier function via downregulating the IL-6/STAT3 signaling [ 281 ]. The anti-inflammatory effect of COS has also recently attracted strong attention.…”

Evaluation of Anti-Colitis Effect of KM1608 and Biodistribution of Dehydrocostus Lactone in Mice Using Bioimaging Analysis

“…Dehydrocostus lactone is an active compound from Aucklandia lappa and inhibits lipopolysaccharide (LPS)-induced TNF-α production in RAW 264.7 cells and mice [ 26 ]. Moreover, it has recently been reported that the oral administration of dehydrocostus lactone ameliorates DSS-induced colitis via the reduction of the expression of proinflammatory cytokines, such as TNF-α, IL-1β, IL-6, and IL-17 [ 27 , 28 ].…”