The First School of Clinical Medicine of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China; Key Laboratory of Digestive Pathophysiology of Zhejiang Province, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, China.
The First School of Clinical Medicine of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Department of Radiology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China; Department of Neurology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou 310006, China.
Biochem Pharmacol. 2023 Nov;217:115845. doi: 10.1016/j.bcp.2023.115845. Epub 2023 Oct 10.
Inflammatory bowel diseases (IBD) represent chronic gastrointestinal inflammatory disorders characterized by a complex and underexplored pathogenic mechanism. Previous research has revealed that IBD patients often have a deficiency of choline and its metabolites, including acetylcholine (ACh) and phosphatidylcholine (PC), within the colon. However, a comprehensive study linking these three substances and their mechanistic implications in IBD remains lacking. This study aimed to investigate the efficacy and underlying mechanism of cytidine diphosphate (CDP)-choline (citicoline), an intermediate product of choline metabolism, in a mouse model of IBD induced by dextran sulfate sodium salt (DSS). The results demonstrated that CDP-choline effectively alleviated colonic inflammation and deficiencies in choline, ACh, and PC by increasing the raw material. Further detection showed that CDP-choline also increased the ACh content by altering the expression of high-affinity choline transporter (ChT1) and acetylcholinesterase (AChE) in DSS-induced mice colon. Moreover, CDP-choline increased the expression of alpha7 nicotinic acetylcholine receptor (α7 nAChR) and activated the cholinergic anti-inflammatory pathway (CAP), leading to reduced colon macrophage activation and proinflammatory M1 polarization in IBD mice, thus reducing the levels of TNF-α and IL-6. In addition, CDP-choline reduced intestinal ecological imbalance and increased the content of hexanoic acid in short-chain fatty acids (SCFAs) in mice. In conclusion, this study elucidates the ability of CDP-choline to mitigate DSS-induced colon inflammation by addressing choline and its metabolites deficiencies, activating the CAP, and regulating the composition of the intestinal microbiome and SCFAs content, providing a potential prophylactic and therapeutic approach for IBD.
炎症性肠病（IBD）是一种慢性胃肠道炎症性疾病，其发病机制复杂且尚未完全阐明。既往研究发现，IBD 患者的结肠中胆碱及其代谢物（包括乙酰胆碱（ACh）和磷脂酰胆碱（PC））常常存在缺乏。然而，目前仍缺乏将这三种物质联系起来并探讨其在 IBD 中的机制意义的全面研究。本研究旨在探讨胞苷二磷酸（CDP）-胆碱（胞磷胆碱）在葡聚糖硫酸钠（DSS）诱导的 IBD 小鼠模型中的疗效及其潜在机制。研究结果表明，CDP-胆碱通过增加原料有效缓解了结肠炎症以及胆碱、ACh 和 PC 的缺乏。进一步的检测显示，CDP-胆碱还通过改变 DSS 诱导的小鼠结肠中高亲和力胆碱转运体（ChT1）和乙酰胆碱酯酶（AChE）的表达，增加了 ACh 的含量。此外，CDP-胆碱增加了α7 型烟碱型乙酰胆碱受体（α7 nAChR）的表达并激活了胆碱能抗炎途径（CAP），从而减少了 IBD 小鼠结肠中巨噬细胞的激活和促炎 M1 极化，降低了 TNF-α和 IL-6 的水平。此外，CDP-胆碱减少了肠道生态失衡并增加了短链脂肪酸（SCFAs）中己酸的含量。综上所述，本研究阐明了 CDP-胆碱通过解决胆碱及其代谢物缺乏、激活 CAP 以及调节肠道微生物组组成和 SCFAs 含量来减轻 DSS 诱导的结肠炎症的能力，为 IBD 的预防和治疗提供了一种潜在的方法。
