Dehydroepiandrosterone (DHEA) possess anti-inflammatory, anti-oxidant and immune-regulating function in animals and humans, but there is not enough information about the mechanisms underlying its beneficial effects. The present study investigated the effect and mechanism of DHEA in dextran sulfate sodium (DSS)-induced colitis mice. The findings showed that DHEA relieved the decreasing of body weight, the increasing of disease activity index, the enhancing of spleen weight, the shortening of colon length and the rising of myeloperoxidase activity; meanwhile, histopathological analysis showed that DHEA maintained a relatively intact structure of colon in DSS-induced colitis mice. DHEA decreased the malondialdehyde content, superoxide dismutase activity and inducible nitric oxide synthase protein level; meanwhile, DHEA also inhibited the secretion of tumor necrosis factor-α, interleukin-1β and interleukin-6 in DSS-induced colitis mice. Importantly, our results showed that DHEA blocked the activation of nuclear factor-kappa B (NF-κB) and p38 mitogen-activated protein kinase (MAPK) pathways; and it inhibited the Nod-like receptor protein 3 inflammasome activation in DSS-induced colitis mice. Furthermore, DHEA markedly promoted the intestinal barrier function by up-regulation zonula occludens-1 expression level. The 16S rDNA gene sequencing demonstrated that DHEA decreased the Pseudomonas abundance in DSS-induced colitis mice. In conclusion, our data demonstrated that DHEA reduces oxidative damage through regulating antioxidant enzyme activity; inhibits pro-inflammatory cytokines production by blocking the activation of p38 MAPK and NF-κB signal pathway; protects colon barrier integrity via increasing tight junction protein expression and modulating gut microbiota taxa; all that finally alleviates DSS-induced experimental colitis in mice.

中文翻译：

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脱氢表雄酮对硫酸葡聚糖钠诱导的结肠炎小鼠免疫反应和肠道菌群的影响。

脱氢表雄酮（DHEA）在动物和人类中具有抗炎，抗氧化和免疫调节功能，但尚无足够的信息了解其有益作用的潜在机制。本研究探讨了脱氢表雄酮（DHEA）在硫酸右旋糖酐钠（DSS）诱导的结肠炎小鼠中的作用和机制。结果表明，脱氢表雄酮减轻了体重的减轻，疾病活动指数的增加，脾脏重量的增加，结肠长度的缩短和髓过氧化物酶活性的增加。同时，组织病理学分析表明，DHEA在DSS诱导的结肠炎小鼠中维持了相对完整的结肠结构。DHEA降低了丙二醛含量，超氧化物歧化酶活性和诱导型一氧化氮合酶蛋白水平；同时，DHEA还抑制DSS诱发的结肠炎小鼠的肿瘤坏死因子-α，白介素1β和白介素6的分泌。重要的是，我们的结果表明DHEA阻断了核因子-κB（NF-κB）和p38丝裂原激活的蛋白激酶（MAPK）通路的激活。并能抑制DSS诱导的结肠炎小鼠Nod样受体蛋白3炎性小体的活化。此外，DHEA通过上调小带闭塞1表达水平显着促进肠屏障功能。16S rDNA基因测序表明，DHEA降低了DSS诱导的结肠炎小鼠中的假单胞菌丰度。总之，我们的数据表明DHEA通过调节抗氧化酶的活性来减少氧化损伤。通过阻断p38 MAPK和NF-κB信号通路的激活来抑制促炎细胞因子的产生；通过增加紧密连接蛋白的表达和调节肠道菌群来保护结肠屏障的完整性；所有这些最终减轻了DSS诱发的小鼠实验性结肠炎。