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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Immunological Tolerance and Regulation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1529660
This article is part of the Research Topic Immunometabolism in Immunological Tolerance and Regulation: Novel Mechanisms and Clinical Interventions View all articles

1-Methylnicotinamide Modulates IL-10 Secretion and Voriconazole Metabolism

Provisionally accepted
Xiaoyan Deng Xiaoyan Deng 1Yuanqing Li Yuanqing Li 1Lin Jiang Lin Jiang 1Maoxun Yang Maoxun Yang 2Xiaokang Wang Xiaokang Wang 2*
  • 1 Guangdong Medical University, Zhanjiang, Guangdong, China
  • 2 Guangdong Provincial Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China

The final, formatted version of the article will be published soon.

    BackgroundInflammatory diseases impair the hepatic metabolism of voriconazole (VRC). 1-Methylnicotinamide (1-MNA), a common final metabolite of nicotinamide in the liver, has demonstrated anti-inflammatory effects in recent studies. This study investigated the impact of 1-MNA on VRC metabolism in the liver.MethodMice with a systemic inflammatory response induced by lipopolysaccharide (LPS) were intragastrically administered 1-MNA, and their VRC metabolic capacity was evaluated. Kupffer cells and primary hepatocytes were isolated, and flow cytometry along with molecular knockdown experiments were performed to explore the molecular mechanisms underlying improved drug metabolism. IL-10 knockout (IL-10–/–) mice were used to validate the role of IL-10 in enhancing hepatocyte VRC metabolism under inflammatory conditions.Results1-MNA promoted M2 polarization of liver Kupffer cells, stimulated IL-10 secretion, upregulated CYP2C38 expression in primary hepatocytes, and enhanced VRC metabolism. The mechanism by which IL-10 upregulated CYP2C38 appears to involve the inhibition of the nuclear transcription factor NF-κB (p65) in hepatocytes.Conclusions1-MNA regulated Kupffer cell polarization in an LPS-induced inflammatory environment, reduced the inflammatory inhibition of CYP2C38 expression in hepatocytes, and promoted VRC metabolism.

    Keywords: 1-Methylnicotinamide, Kupffer Cells, Hepatocytes, Voriconazole, CYP2C19, Metabolism

    Received: 17 Nov 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Deng, Li, Jiang, Yang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xiaokang Wang, Guangdong Provincial Key Laboratory for Research and Development of Natural Drugs, School of Pharmacy, Guangdong Medical University, Dongguan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.