Anti-inflammatory Actions of (+)-3′α-Angeloxy-4′-keto-3′,4′-dihydroseselin (Pd-Ib) against Dextran Sulfate Sodium-Induced Colitis in C57BL/6 Mice

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• 作者：Huai-Xue Mu ; Jing Liu ; Sarwat Fatima ; Cheng-Yuan Lin ; Xiao-Ke Shi ; Bin Du ; Hai-Tao Xiao ; Bao-Min Fan ; Zhao-Xiang Bian
• 刊名：Journal of Natural Products
• 出版年：2016
• 出版时间：April 22, 2016
• 年：2016
• 卷：79
• 期：4
• 页码：1056-1062
• 全文大小：682K
• 年卷期：0
• ISSN：1520-6025

文摘

The immunoregulatory protective properties of (+)-3′α-angeloxy-4′-keto-3′,4′-dihydroseselin (Pd-Ib) isolated from Bupleurum malconense has not been reported. In the present study, the therapeutic effect of Pd-Ib (30, 60, and 120 mg/kg/day) was examined in a mouse model of dextran sulfate sodium (DSS)-induced acute colitis. Administration of Pd-Ib significantly reduced the disease activity index, inhibited the shortening of colon length, reduced colonic tissue damage, and suppressed colonic myeloperoxidase activity and nitric oxide levels in mice with DSS-induced colitis. Moreover, Pd-Ib greatly suppressed the secretion of pro-inflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17A while enhancing the level of anti-inflammatory cytokine IL-4. The protein levels of phosphorylated STAT3 (p-STAT3) and phosphorylated p38 (p-p38) were down-regulated in the colonic tissues of DSS-treated mice. Importantly, the anti-inflammatory effect of Pd-Ib against acute colitis was comparable to the anti-inflammatory sulfa drug sulfasalazine (300 mg/kg). Furthermore, the in vitro study showed that the inhibitory effect of Pd-Ib on p-STAT3 and IL-6 protein levels was accompanied by the reduction of MAPKs (JNK and p38). In conclusion, this study suggested that Pd-Ib attenuated DSS-induced acute colitis via the regulation of interleukins principally through the STAT3 and MAPK pathways.