Page 258 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-75

The anti-inflammatory effects of machinolide A from Machilus zuihoensis var.

mushaensis of human neutrophils

2
,1
#,1
Pei-Fang Sun, Hsun-Shuo Chang, Hsiang-Ruei Liao*

1 Graduate Institute of Natural Products, College of Medicine, Chang Gung University,
Taoyuan 333, Taiwan, Republic of China
2 Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical
University, Kaohsiung 807, Taiwan, Republic of China
* E-mail: liaoch@mail.cgu.edu.tw

Abstract
Neutrophils are central effectors of innate immunity that eliminate pathogens via
phagocytosis, oxidative burst, and degranulation, whereas hyperactivation causes tissue injury.
Machinolide A, a γ-butyrolactone from the Taiwanese Lauraceae species Machilus zuihoensis
var. mushaensis, was evaluated for its modulation of human neutrophils. It inhibits N-
formylmethionyl-leucyl-phenylalanine (fMLP)–induced reactive oxygen species (ROS)
production and cathepsin G (CG) release in a concentration-dependent manner (IC₅₀ = 16.37 ±
2.62 and 7.01 ± 0.53 μM, respectively) . The compound was non-cytotoxic at the tested
concentrations. Machinolide A (50 μM) attenuated the fMLP-induced increase in intracellular
Ca²⁺. At the same concentration, NADPH oxidase 2 (NOX2) activity was unchanged; xanthine
oxidase activity and formyl peptide receptor binding were likewise unaffected. Under fMLP
stimulation, immunoblotting demonstrated selective attenuation of ERK1/2, p38 mitogen-
activated protein kinase (p38 MAPK), and protein kinase B (Akt) phosphorylation
(Thr308/Ser473); by contrast, phorbol 12-myristate 13-acetate (PMA)–driven, protein kinase
C (PKC)–dependent signaling was not significantly inhibited. Collectively, these results
indicate that Machinolide A selectively attenuates fMLP-stimulated oxidative burst and
degranulation via mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase–
Akt (PI3K–Akt) pathways, supporting its potential as a natural anti-inflammatory lead for
neutrophil-associated pathologies.

Keywords: Machilus zuihoensis var. mushaensis; Machinolide A; Neutrophil; fMLP; γ-butyro-
lactone