2. Academic Validation
  3. Garcinoic acid enhances inflammation resolution against colitis by activating Nrf2 dependent efferocytosis

Garcinoic acid enhances inflammation resolution against colitis by activating Nrf2 dependent efferocytosis

  • Free Radic Biol Med. 2025 Sep:237:37-45. doi: 10.1016/j.freeradbiomed.2025.05.428.
Ibrahim Isot 1,  Seong Hoon Kim 2,  Tugce Demirel-Yalciner 3,  Anna Migni 4,  Antimo Gioiello 5,  Francesco Galli 4,  Erdi Sozen 6,  Young-Joon Surh 2,  Nesrin Kartal Ozer 7
Affiliations

Affiliations

  • 1 Department of Biochemistry, Faculty of Medicine, Marmara University, Istanbul, Türkiye; Institute of Health Sciences, Marmara University, Istanbul, Türkiye.
  • 2 Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea.
  • 3 Department of Biochemistry, Faculty of Medicine, Uskudar University, Istanbul, Türkiye; Metabolic and Inflammatory Diseases Research Center (METIFLAM), Uskudar University, Istanbul, Türkiye.
  • 4 Unit of Clinical Biochemistry and Human Nutrition, Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
  • 5 Laboratory of Medicinal and Advanced Synthetic Chemistry (Lab MASC), Department of Pharmaceutical Sciences, University of Perugia, Perugia, Italy.
  • 6 Department of Biochemistry, Faculty of Medicine, Marmara University, Istanbul, Türkiye; Genetic and Metabolic Diseases Research and Investigation Center (GEMHAM), Marmara University, Istanbul, Türkiye.
  • 7 Department of Biochemistry, Faculty of Medicine, Uskudar University, Istanbul, Türkiye; Metabolic and Inflammatory Diseases Research Center (METIFLAM), Uskudar University, Istanbul, Türkiye. Electronic address: [email protected].
PMID: 40449807 DOI: 10.1016/j.freeradbiomed.2025.05.428
Abstract

Inflammation resolution represents the most crucial step in the inflammatory response, and its disruption is associated with a variety of disorders. Clearance of apoptotic cells, namely efferocytosis, plays a pivotal role in this process by preventing the transition of apoptotic cell accumulation into necrosis and fibrosis. Garcinoic acid (GA), a plant metabolite and a postbiotics analogue of vitamin E, has been demonstrated to possess anti-inflammatory activity, but mechanistic aspects of this effect remain poorly characterized. In this study, we explored the potential of GA in enhancing efferocytosis and inflammation resolution. In vitro findings using macrophages indicated that GA enhances efferocytosis through the involvement of MerTK, LRP-1, and TIM4, and specialized pro-resolving lipid mediators (SPMs), mainly lipoxin A4 and resolvin E1. As in vivo, GA reduced inflammatory and degenerative symptoms in a mouse model of dextran sodium sulfate (DSS)-induced colitis, which was associated with increased efferocytosis activity in colon. Mechanistically, Nrf2 silencing and HO-1 inhibition in macrophages reduced both efferocytosis and SPMs effects of GA, suggesting that the pro-resolving role of this metabolite may depend, at least partially, on Nrf2 activity and stress response effects. Present findings demonstrate a role of GA as efferocytosis enhancer and potential therapeutic agent in non-resolving diseases.

Keywords

DSS-Induced colitis; Efferocytosis; Garcinoic acid; Inflammation; Macrophage.

Figures
Products