3, 3-Dimethyl-1-butanol attenuates ulcerative colitis and secondary liver injury by reducing trimethylamine production

WANG Xinnan; LIU Lifang

doi:10.11665/j.issn.1000-5048.2023080801

Journal of China Pharmaceutical University > 2024 > 55(2): 246-256. > DOI: 10.11665/j.issn.1000-5048.2023080801

WANG Xinnan, LIU Lifang. 3, 3-Dimethyl-1-butanol attenuates ulcerative colitis and secondary liver injury by reducing trimethylamine production[J]. J China Pharm Univ, 2024, 55(2): 246 − 256. DOI: 10.11665/j.issn.1000-5048.2023080801

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3, 3-Dimethyl-1-butanol attenuates ulcerative colitis and secondary liver injury by reducing trimethylamine production

WANG Xinnan^{1, 2,},
LIU Lifang^1, ,

1.
Department of Pharmacognosy, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198
2.
Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, China

Funds: This study was supported by the National Natural Science Foundation of China (No. 82074089)

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Received Date: August 07, 2023

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Abstract

Ulcerative colitis (UC) is a chronic intestinal disease caused by a variety of factors. Severe intestinal inflammation can also cause liver injury. Based on the previous research, microbial dysbiosis in the inflammatory state leads to the conversion of excess choline into trimethylamine (TMA) by the intestinal flora, which competes with the host for the use of the nutrient choline, and induces liver injury. 3, 3-dimethyl-1-butanol (DMB), a structural analogue of choline, can reduce TMA levels from choline conversion. The aim of this study was to investigate the protective effect and possible mechanism of DMB on UC and secondary liver injury. Dextran sulfate sodium-induced acute colitis model in mice was established. The weight of mice, and collected serum, liver and intestinal contents after mice sacrifice were measured. The morphological changes of colon and liver were observed; liver function was detected with the kit of biochemical indexes; UHPLC-MS/MS was applied to detect changes in choline metabolism in vivo. The experimental results showed that DMB could attenuate body weight loss index, improve colonic inflammation, and reduce liver injury in UC mice. The detection of choline-related metabolites in serum, intestinal contents and liver showed that DMB could effectively inhibit the production of trimethylamine in the intestine, improve the availability of host choline, effectively alleviate colitis deterioration, and reduce liver damage caused by severe intestinal lesions.
- choline metabolism,
- colitis,
- gut microbiota metabolism,
- trimethylamine

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