Pseudane-VII Isolated from Pseudoalteromonas sp. M2 Ameliorates LPS-Induced Inflammatory Response In Vitro and In Vivo

Abstract

The ocean is a rich resource of flora, fauna, food, and biological products. We found a wild-type bacterial strain, Pseudoalteromonas sp. M2, from marine water and isolated various secondary metabolites. Pseudane-VII is a compound isolated from the Pseudoalteromonas sp. M2 metabolite that possesses anti-melanogenic activity. Inflammation is a response of the innate immune system to microbial infections. Macrophages have a critical role in fighting microbial infections and inflammation. Recent studies reported that various compounds derived from natural products can regulate immune responses including inflammation. However, the anti-inflammatory effects and mechanism of pseudane-VII in macrophages are still unknown. In this study, we investigated the anti-inflammatory effects of pseudane-VII. In present study, lipopolysaccharide (LPS)-induced nitric oxide (NO) production was significantly decreased by pseudane-VII treatment at 6 μM. Moreover, pseudane-VII treatment dose-dependently reduced mRNA levels of pro-inflammatory cytokines including inos, cox-2, il-1β, tnf-α, and il-6 in LPS-stimulated macrophages. Pseudane-VII also diminished iNOS protein levels and IL-1β secretion. In addition, Pseudane-VII elicited anti-inflammatory effects by inhibiting ERK, JNK, p38, and nuclear factor (NF)-κB-p65 phosphorylation. Consistently, pseudane-VII was also shown to inhibit the LPS-stimulated release of IL-1β and expression of iNOS in mice. These results suggest that pseudane-VII exerted anti-inflammatory effects on LPS-stimulated macrophage activation via inhibition of ERK, JNK, p38 MAPK phosphorylation, and pro-inflammatory gene expression. These findings may provide new approaches in the effort to develop anti-inflammatory therapeutics.

Pseudane-VII Regulates LPS-Induced Neuroinflammation in Brain Microglia Cells through the Inhibition of iNOS Expression

“…As shown in Figure 2 and Figure 3, we found that pseudane-VII significantly inhibits NO production and suppresses the mRNA and protein levels of iNOS and COX-2 in LPS-stimulated BV-2 microglial cells. These results support that our previously reported pseudane-VII inhibited the gene and protein expression levels of iNOS and COX-2, which were increased by LPS stimulation in macrophage [12].…”

“…We found that pseudane-VII selectively suppresses IL-1β protein levels in LPS-stimulated microglia (Figure 4). Interestingly, pseudane-VII selectively inhibited IL-1β in macrophage [12]. This suggests that pseudane-VII has an anti-inflammatory effect through the regulation of IL-1β in macrophage and microglia.…”

“…In previous studies, we used liquid chromatography-mass spectrometry to isolate 4-hydroxy-2-alkylquinoline (pseudane-VII) obtained from the wild-type marine bacterium Pseudoalteromonas sp. M2 [12]. Pseudane-VII is a secondary metabolite that has anti-melanogenic and inflammatory activity [12,13].…”

“…M2 [12]. Pseudane-VII is a secondary metabolite that has anti-melanogenic and inflammatory activity [12,13]. However, the anti-neuroinflammatory properties of pseudane-VII have not been examined.…”

Bacterial Alkyl-4-quinolones: Discovery, Structural Diversity and Biological Properties

“…2-n-heptyl-4-quinolone (H7) from marine Pseudoalteromonas sp. M2 was investigated for its anti-inflammatory activity and proved to be a very promising candidate for neuro-inflammatory disorders, owing to its ability to inhibit NO, ROS production and the expression of iNOS and COX-2 [109,110]. The same compound (H7) proved to be the most potent inhibitor of melanin synthesis when tested for anti-melanogenic activity.…”