山药果皮中的6,7-二羟基-2,4-二甲氧基菲通过调节NF-κB/ COX-2信号通路减轻DSS诱导的小鼠肠道粘膜损伤,Journal of Agricultural and Food Chemistry

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山药果皮中的6,7-二羟基-2,4-二甲氧基菲通过调节NF-κB/ COX-2信号通路减轻DSS诱导的小鼠肠道粘膜损伤
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2021-03-24 , DOI: 10.1021/acs.jafc.1c00487
Qian Li ₁ , Konghui Li ₁ , Tenggen Hu ₁ , Fan Liu ₁ , Sentai Liao ₁ , Yuxiao Zou ₁

Affiliation

在这项研究中，我们评估了山药皮中主要的菲（6,7-二羟基-2,4-二甲氧基菲，CYP4）的保护作用和分子机制。在硫酸葡聚糖硫酸钠（DSS）处理之前，对BALB / c小鼠给予三剂山药酚提取物（CYPE）和山药菲4（CYP4），并以盐酸小ber碱作为阳性对照（PC）。结果表明，预先干预CYPE和CYP4可以改善DSS小鼠的疾病活动指数（DAIs），组织损伤评分（HDS）和存活率，其效率要高于PC。进一步的研究表明，CYP4的表达下调了氧化应激相关因子MPO和NO，并改善了紧密连接蛋白occludin。除了，CYP4处理可显着下调caspase-3的表达和肠上皮细胞的凋亡率。另外，CYP4治疗改善了结肠中炎性细胞因子的产生，包括TNF-α，IFN-γ，IL-10和IL-23。此外，与模型对照组（MC）相比，在CYE4组中ERK1 / 2，NF-κBp65，pNF-κB和COX-2的蛋白表达受到抑制。这些发现表明，CHP4可以在体内实验性UC模型中有效抑制NF-κB/ COX-2的激活。首次证明CYPE和CYP4保护小鼠肠粘膜不受损害，并预防DSS诱导的小鼠结肠炎。CYP4是山药在保护肠道健康中必须具有的生物学作用的有效成分之一。

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6,7-Dihydroxy-2,4-Dimethoxyphenanthrene from Chinese Yam Peels Alleviates DSS-Induced Intestinal Mucosal Injury in Mice via Modulation of the NF-κB/COX-2 Signaling Pathway

In this study, we evaluated the protective effect and molecular mechanism of a dominant phenanthrene, (6,7-dihydroxy-2,4-dimethoxyphenanthrene, CYP4), from Chinese yam peels on intestinal epithelial integrity. Three doses of Chinese yam phenolic extract (CYPE) and Chinese yam phenanthrene 4 (CYP4) were administered to BALB/c mice for 7 days before dextran sulfate sodium (DSS) treatment, with berberine hydrochloride as a positive control (PC). Results showed that both disease activity indexes (DAIs), histological damage score (HDS) and survival rate in DSS mice, were improved with preintervention of CYPE and CYP4, which exhibited better efficiency than PC. Further studies showed that administration of CYP4 downregulated the oxidative stress-associated factors, MPO and NO, and improved tight junction protein occludin. Besides, the CYP4 treatment substantially downregulated the caspase-3 expression and the apoptosis rate of intestinal epithelial cells. In addition, the CYP4 treatment ameliorated the production of inflammatory cytokines including TNF-α, IFN-γ, IL-10, and IL-23 in the colon. Furthermore, the protein expression of ERK1/2, NF-κB p65, pNF-κB, and COX-2 was suppressed in CYE4 groups as compared with that in model control (MC). These findings suggested that CHP4 could effectively inhibit the activation of NF-κB/COX-2 in an experimental UC model in vivo. It was demonstrated for the first time that CYPE and CYP4 protected intestinal mucosa from damage and prevented DSS-induced colitis in mice. CYP4 was one of the active principles obligatory for the biological effect of Chinese yam in protecting intestinal health. These findings indicated that CYP4 might be a promising and useful approach for treatment of UC in humans.

更新日期：2021-04-29

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