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猪苓健脾胶囊对实验性溃疡性结肠炎的治疗作用及其化学成分表征与基于超高效液相色谱-四极杆飞行时间质谱的代谢组学研究

Therapeutic effects of Zhuling Jianpi capsule on experimental ulcerative colitis and characterization of its chemical constituents and metabolomics using UHPLC-Q-TOF-MS.

作者信息

Li Jian, Zhou Ziqi, Liu Dan, Dong Haijuan, Zhou Jianping, Wu Jie

机构信息

Department of Pharmaceutics, China Pharmaceutical University, Nanjing, China.

Jinling Pharmaceutical Co., Ltd., Nanjing, China.

出版信息

Heliyon. 2023 May 24;9(6):e16553. doi: 10.1016/j.heliyon.2023.e16553. eCollection 2023 Jun.

Abstract

Zhuling Jianpi Capsule (Zhuling) is a traditional Chinese medicinal formula used to treat symptoms such as abdominal pain, bloating and diarrhea associated with inflammatory bowel disease (IBD). However, the protective effects of Zhuling on experimental ulcerative colitis (UC) and the effective substance responsible for its efficacy have rarely been reported. In this study, we evaluated the therapeutic effects of orally administrated Zhuling on DSS-induced UC in mice. The chemical constituents and metabolomics of Zhuling were qualitatively analyzed by ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The results showed that Zhuling treatment markedly alleviated DSS-induced clinical symptoms, restrained the secretion of pro-inflammatory cytokines, and improved intestinal epithelial barrier function. Furthermore, a total of 167 compounds have been identified or characterized, and 120 prototype components were detected in the urine, plasma, bile and feces of mice. Among them, altogether 26 representative prototypes were associated with 139 metabolites via the corresponding biotransformation pathways, and both of them mainly contained flavonoids, alkaloids, organic acids, monoterpenes, phenylpropanoids, triterpenoids, sesquiterpenoids and anthraquinones. Finally, 12 potent compounds mainly containing flavonoids, terpenoids and phenylpropanoids were screened out as potential quality control index components and might be the main substances that exert a pharmacological effect. Our data indicated that Zhuling administration prominently alleviates DSS-induced colitis in mice. Additionally, the chemical and metabolic profiling provided helpful information on the potential pharmacodynamic substances of Zhuling, which can be further investigated in the future.

摘要

猪苓健脾胶囊(猪苓)是一种用于治疗与炎症性肠病(IBD)相关的腹痛、腹胀和腹泻等症状的中药方剂。然而,猪苓对实验性溃疡性结肠炎(UC)的保护作用及其疗效的有效物质鲜有报道。在本研究中,我们评估了口服猪苓对小鼠葡聚糖硫酸钠(DSS)诱导的UC的治疗效果。采用超高效液相色谱-四极杆飞行时间质谱联用(UHPLC-Q-TOF-MS)对猪苓的化学成分和代谢组学进行了定性分析。结果表明,猪苓治疗显著减轻了DSS诱导的临床症状,抑制了促炎细胞因子的分泌,并改善了肠道上皮屏障功能。此外,共鉴定或表征了167种化合物,在小鼠尿液、血浆、胆汁和粪便中检测到120种原型成分。其中,共有26种代表性原型通过相应的生物转化途径与139种代谢产物相关,两者主要含有黄酮类、生物碱、有机酸、单萜类、苯丙素类、三萜类、倍半萜类和蒽醌类。最后,筛选出12种主要含有黄酮类、萜类和苯丙素类的有效化合物作为潜在的质量控制指标成分,可能是发挥药理作用的主要物质。我们的数据表明,给予猪苓可显著减轻小鼠DSS诱导的结肠炎。此外,化学和代谢谱分析为猪苓潜在的药效物质提供了有用信息,未来可进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/891e/10238897/27428d4d7869/ga1.jpg

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