PB1381 - MCF-32, a new extract from the fruit of Myristica cagayanesis, inhibits fMLP-induced superoxide anion production by specific targeting the Akt in human neutrophils

Tuesday, June 25, 2024

13:45 – 14:45 ICT

Room: Exhibition Hall

Presenting Author(s)

HL

Hsiang Ruei Liao, PhD

Professor
Graduate Institute of Natual Products, College of Medicine, Chang-Gung Univesity
Kwei-Shan, Taoyuan, Taiwan (Republic of China)

Co-Author(s)

yk

yu-yao kao

master student
Graduate Institute of Natural Products, College of Medicine, Chang-Gung University
Kwei-shan, Taoyuan, Taiwan (Republic of China)
JC

Jih-Jung Chen

Professor
Department of Pharmacy, National Yan Ming Chiao Tung University
Taipei, Taipei, Taiwan (Republic of China)
FL

Fu-Chao Liu

professor
Department of Anesthesiology, Chang Gung Memorial Hospital
Kwei-Shan, Taoyuan, Taiwan (Republic of China)
CT

Ching-Ping Tseng

Professor
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University
Kwei-Shan, Taoyuan, Taiwan (Republic of China)

Background: The over-activated neutrophils through G-protein-coupled receptors (GPCRs) caused inflammation or tissue damage. Therefore, GPCRs or their downstream molecules are significant targets for inhibiting uncontrolled neutrophil activation.

Aims: Our studies investigate the action and underlying mechanism of MCF-32, an extract from the fruit of Myristica cagayanensis, on fMLP-induced neutrophil respiratory burst, chemotaxis, and granular release.

Methods: This assay investigated whether MCF-32 inhibits fMLP-induced respiratory burst by specifically interfering with the Akt induced by the fMLP receptor with its downstream molecules.

Results: Briefly, larixol inhibited fMLP (0.1 μM)-induced superoxide anion production (IC50:4.73±0.68 μM) in a concentration-dependent manner; however, MCF-32 did not inhibit these functions induced by PMA (100 nM). MCF-32 inhibited fMLP-induced Akt kinase phosphorylation and phosphorated-Akt translocation to the cellular membrane. Therefore, MCF-32 attenuated the downstream signaling of Akt kinases, p47, and Rac2 translocation from the cytosol to the membrane. Moreover, MCF-32 did not inhibit fMLP-induced intracellular calcium mobilization or PKC phosphorylation. MCF-32 did not inhibit Src kinase or PDK1 activation by fMLP stimulation. Furthermore, MCF-32 did not antagonize the formyl peptide receptors. MCF-32 did not increase cyclic nucleotide levels in neutrophils.

Conclusion(s): These results suggest that MCF-32 modulated fMLP-induced neutrophils superoxide anion production and granular releases by explicitly inhibiting the Akt activation induced by the fMLP receptor.