Myriscagayanone C, a new compound from the fruit of myristica cagayanensis, inhibits fMLP-induced respiratory bursts by specifically preventing Akt translocation in human neutrophils.

Chem Biol Interact

Department of Pharmacy, School of Pharmaceutical, National Yang Ming Chiao Tuang University, Taipei, Taiwan, Republic of China; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address:

Published: December 2024

Neutrophils that are overactivated can cause inflammatory diseases. Neutrophils possess various surface receptors, including G-protein-coupled chemoattractant receptors, which assist in recognizing pathogen attacks and the inflammatory environment. Therefore, targeting G-protein-coupled chemoattractant receptors and their downstream molecules is important for preventing abnormal neutrophil activation. This study examines the effects and underlying mechanism of myriscagayanone C, a new compound obtained from the fruit of myristica cagayanensis, on neutrophil respiratory burst induced by fMLP. The immunoblotting assay was conducted to assess the mechanisms by which myriscagayanone C inhibits fMLP-induced respiratory burst by disrupting the translocation of Akt to the cellular membrane. Briefly, myriscagayanone C suppressed the production of superoxide anions induced by fMLP on human neutrophils in a concentration-dependent manner (IC: 4.73±0.68 μM). Myriscagayanone C blocked fMLP-induced Akt translocation to the cell membrane, inhibiting Akt and Akt phosphorylation by PDK1 and mTOR, respectively. Myriscagayanone C inhibited fMLP-induced p47 phosphorylation and translocation. Myriscagayanone C did not inhibit the activity of PI3K, the amount of phosphatidylinositol (3, 4, 5)-trisphosphate, or the translocation of phosphorylated-PDK1 and -mTOR to the membrane. Myriscagayanone C did not inhibit fMLP-induced PKC, Src, ERK1/2, p38 phosphorylation, and intracellular calcium mobilization. Myriscagayanone C did not inhibit the chemotaxis and CD11b expression induced by fMLP. Myriscagayanone C did not inhibit PMA-induced superoxide anion production and neutrophil extracellular trap formation. According to this data, myriscagayanone C inhibits fMLP-induced neutrophil superoxide anion production by interrupting the translocation of Akt to the plasma membrane, which affects the NADPH oxidase activity by preventing p47 phosphorylation and translocation.

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http://dx.doi.org/10.1016/j.cbi.2024.111357DOI Listing

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Myriscagayanone C, a new compound from the fruit of myristica cagayanensis, inhibits fMLP-induced respiratory bursts by specifically preventing Akt translocation in human neutrophils.

Chem Biol Interact

December 2024

Department of Pharmacy, School of Pharmaceutical, National Yang Ming Chiao Tuang University, Taipei, Taiwan, Republic of China; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan; Traditional Herbal Medicine Research Center, Taipei Medical University Hospital, Taipei, Taiwan. Electronic address:

Neutrophils that are overactivated can cause inflammatory diseases. Neutrophils possess various surface receptors, including G-protein-coupled chemoattractant receptors, which assist in recognizing pathogen attacks and the inflammatory environment. Therefore, targeting G-protein-coupled chemoattractant receptors and their downstream molecules is important for preventing abnormal neutrophil activation.

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