2. Academic Validation
  3. Ascorbyl palmitate ameliorates inflammatory diseases by inhibition of NLRP3 inflammasome

Ascorbyl palmitate ameliorates inflammatory diseases by inhibition of NLRP3 inflammasome

  • Int Immunopharmacol. 2024 Apr 20:131:111915. doi: 10.1016/j.intimp.2024.111915.
Luchen Zhang 1,  Guoyang Li 1,  Bolong Lin 1,  Hongbin He 2,  Rongbin Zhou 3,  Wei Jiang 4
Affiliations

Affiliations

  • 1 Department of Geriatrics, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of Institute of Health and Medicine (IHM), University of Science and Technology of China, Hefei, China; Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.
  • 2 Department of Geriatrics, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of Institute of Health and Medicine (IHM), University of Science and Technology of China, Hefei, China; Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. Electronic address: hhb123@ustc.edu.cn.
  • 3 Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. Electronic address: zrb1980@ustc.edu.cn.
  • 4 Department of Geriatrics, First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, Center for Advanced Interdisciplinary Science and Biomedicine of Institute of Health and Medicine (IHM), University of Science and Technology of China, Hefei, China; Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China. Electronic address: ustcjw@ustc.edu.cn.
PMID: 38522141 DOI: 10.1016/j.intimp.2024.111915
Abstract

The aberrant activation of NLRP3 inflammasome contributes to pathogenesis of multiple inflammation-driven human diseases. However, the medications targeting NLRP3 inflammasome are not approved for clinic use to date. Here, we show that ascorbyl palmitate (AP), a lipophilic derivative of ascorbic acid (AA) and a safe food additive, is a potent inhibitor of NLRP3 inflammasome. Compared with AA, AP inhibited the activation of NLRP3 inflammasome with increased potency and specificity. Mechanistically, AP directly scavenged mitochondrial Reactive Oxygen Species (mitoROS) by its antioxidant activity and blocked NLRP3-NEK7 interaction and NLRP3 inflammasome assembly. Moreover, AP showed more significant preventive effects than AA in LPS-induced systemic inflammation, dextran sulfate sodium (DSS)-induced colitis and experimental autoimmune encephalomyelitis (EAE). Thus, our results suggest that AP is a potential therapeutic combating NLRP3-driven diseases.

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