In Vitro Mechanistic Study of the Anti-inflammatory Activity of a Quinoline Isolated from Spondias pinnata Bark

The search for new plant-based anti-inflammatory
drugs continues in order to overcome the detrimental side effects
of conventional anti-inflammatory agents, both steroidal and nonsteroidal.
This study involves the quinoline SPE2, 7-hydroxy-6-methoxyquinolin-2­(1H)-one, isolated from the EtOAc fraction of Spondias pinnata bark. Structure elucidation was
done using analytical spectroscopic methods including Fourier transform
infrared spectroscopy, high-resolution electrospray ionization mass
spectrometry, nuclear magnetic resonance spectroscopy, and single-crystal
X-ray crystallography. The anti-inflammatory activity of SPE2 was
evaluated in a lipopolysaccharide (LPS)-stimulated murine macrophage
RAW 264.7 model. SPE2 effectively suppressed LPS-induced overproduction
of pro-inflammatory mediators such as nitric oxide (NO), tumor necrosis
factor (TNF)-α, interleukin (IL)-6, and IL-1β, and reactive
oxygen species. Expression levels of NO synthesizing enzyme, cyclooxygenase-2,
TNF-α, IL-6 and IL-1β were also determined to return to
normal after SPE2 treatment. Localization of NF-κB was evaluated
by confocal microscopy and Western blotting, which showed a dose-dependent
reduction of NF-κB inside the nucleus and an increase in cytoplasmic
NF-κB with SPE2 treatment. Collectively, the results suggest
that SPE2 has anti-inflammatory activity via inhibition of NF-κB
activation.