色氨酸代谢物 Indole-3-Carboxaldehyde 通过平衡氨基酸代谢、抑制肠道炎症和改善肠道屏障功能来减轻 DSS 诱导的小鼠溃疡性结肠炎,Molecules

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色氨酸代谢物 Indole-3-Carboxaldehyde 通过平衡氨基酸代谢、抑制肠道炎症和改善肠道屏障功能来减轻 DSS 诱导的小鼠溃疡性结肠炎
Molecules ( IF 4.2 ) Pub Date : 2023-04-25 , DOI: 10.3390/molecules28093704
Mingfei Liu _{1,

2} , Yuxuan Wang _{1,

2} , Haixin Xiang _{1,

2} , Meng Guo _{1,

2} , Shirong Li _{3,

4} , Ming Liu _{1,

2} , Jingchun Yao _{3,

4}

Affiliation

溃疡性结肠炎 (UC) 因其对生活质量的负面影响和增加结直肠癌的风险而备受关注。化学和生物药物是目前UC的常用治疗方法。这些药物总是会引起严重的副作用，或者患者可能会对这些疗法产生耐药性。因此，迫切需要针对 UC 的新治疗选择。在这项研究中，我们通过靶向 TLR4/NF-κB/p38 信号通路，发现了肠道色氨酸代谢物吲哚-3-甲醛 (3-IAld) 在葡聚糖硫酸钠盐 (DSS) 诱导的 UC 小鼠中的抑制活性。该化合物有效地防止结肠长度缩短和 DSS 在结肠中引起的损伤，显着降低炎症的严重程度。TNF-α、IL-6等炎症因子的产生，和 IL-1β 在体内和体外用 3-IAld 处理时显着减弱。这可能归因于 TLR4/NF-kB/p38 信号通路的抑制。此外，3-IAld 可以在体内和体外上调 ZO-1 和 Occludin 的表达。同时，液相色谱质谱（LC-MS）结果表明，3-IAld可以平衡DSS诱导的结肠炎小鼠血清中的天冬氨酸和谷氨酸代谢以及赖氨酸降解代谢。总之，3-IAld改善了DSS诱导的UC小鼠的肠屏障功能障碍和炎症反应，平衡了氨基酸代谢，抑制了TLR4/NF-kB/p38信号通路的激活，从而保护了结肠炎小鼠。此外，3-IAld 可以在体内和体外上调 ZO-1 和 Occludin 的表达。同时，液相色谱质谱（LC-MS）结果表明，3-IAld可以平衡DSS诱导的结肠炎小鼠血清中的天冬氨酸和谷氨酸代谢以及赖氨酸降解代谢。总之，3-IAld改善了DSS诱导的UC小鼠的肠屏障功能障碍和炎症反应，平衡了氨基酸代谢，抑制了TLR4/NF-kB/p38信号通路的激活，从而保护了结肠炎小鼠。此外，3-IAld 可以在体内和体外上调 ZO-1 和 Occludin 的表达。同时，液相色谱质谱（LC-MS）结果表明，3-IAld可以平衡DSS诱导的结肠炎小鼠血清中的天冬氨酸和谷氨酸代谢以及赖氨酸降解代谢。总之，3-IAld改善了DSS诱导的UC小鼠的肠屏障功能障碍和炎症反应，平衡了氨基酸代谢，抑制了TLR4/NF-kB/p38信号通路的激活，从而保护了结肠炎小鼠。液相色谱质谱（LC-MS）结果表明，3-IAld 可以平衡 DSS 诱导的结肠炎小鼠血清中的天冬氨酸和谷氨酸代谢以及赖氨酸降解代谢。总之，3-IAld改善了DSS诱导的UC小鼠的肠屏障功能障碍和炎症反应，平衡了氨基酸代谢，抑制了TLR4/NF-kB/p38信号通路的激活，从而保护了结肠炎小鼠。液相色谱质谱（LC-MS）结果表明，3-IAld 可以平衡 DSS 诱导的结肠炎小鼠血清中的天冬氨酸和谷氨酸代谢以及赖氨酸降解代谢。总之，3-IAld改善了DSS诱导的UC小鼠的肠屏障功能障碍和炎症反应，平衡了氨基酸代谢，抑制了TLR4/NF-kB/p38信号通路的激活，从而保护了结肠炎小鼠。

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The Tryptophan Metabolite Indole-3-Carboxaldehyde Alleviates Mice with DSS-Induced Ulcerative Colitis by Balancing Amino Acid Metabolism, Inhibiting Intestinal Inflammation, and Improving Intestinal Barrier Function

Ulcerative colitis (UC) has attracted much attention for its negative influence on quality of life and increased risk of colorectal cancer. Chemical and biological drugs are currently the usual treatment for UC. These drugs always induce severe side effects, or patients might become resistant to these therapies. Therefore, new therapeutic options for UC are urgently needed. In this study, we discovered the inhibitory activity of the intestinal tryptophan metabolite indole-3-carboxaldehyde (3-IAld) in dextran sulfate sodium salt (DSS)-induced UC mice by targeting the TLR4/NF-κB/p38 signaling pathway. This compound effectively protected against colon length shortening and damage induced by DSS in the colon, notably reducing the severity of inflammation. The production of inflammatory factors of TNF-α, IL-6, and IL-1β was significantly attenuated when treating with 3-IAld in vivo and vitro. This might be attributed to inhibition of the TLR4/NF-kB/p38 signaling pathway. Moreover, 3-IAld could up-regulate the expression of ZO-1 and Occludin in vivo and vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) results showed that 3-IAld could balance the aspartate and glutamate metabolism and the lysine degradation metabolism in the serum of DSS-induced colitis mice. In conclusion, 3-IAld ameliorated the intestinal barrier dysfunction and inflammatory response in DSS-induced UC mice, balanced amino acid metabolism, and inhibited the activation of the TLR4/NF-kB/p38 signaling pathway, thereby protecting mice with colitis.

更新日期：2023-04-25

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