Oscarellin, an Anthranilic Acid Derivative from a Philippine Sponge, Oscarella stillans, as an Inhibitor of Inflammatory Cytokines in Macrophages

Abstract

A new anthranilic acid derivative (1) was isolated from a Philippine sponge, Oscarella stillans (Bergquist and Kelly). The structure of compound 1, named oscarellin, was determined as 2-amino-3-(3'-aminopropoxy)benzoic acid from spectroscopic data and confirmed by synthesis. We examined the immunomodulating effect of compound 1 and its mechanism in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Our data indicated that the expression of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6 were significantly reduced by the pretreatment of 1 (0.1-10 μM) for 2 h. In addition, compound 1 suppressed activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and c-Jun NH-termimal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK) in LPS-stimulated RAW 264.7 cells. Compound 1 abrogated LPS-induced nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) activities, whereas the induction of activating transcription factor-3 (ATF-3) was increased. Taken together, our results suggest that compound 1 attenuates pro-inflammatory cytokines via the suppression of JNK, ERK, AP-1, and NF-κB and the activation of the ATF-3 signaling pathway.

Marine natural products

“…416 Four new amino acid compounds 1015-1018 were reported from the sponge genera Hymeniacidon, Lendenfeldia and Oscarella; the synthesis of the last compound was also achieved. [417][418][419] Pyrazole NPs 1019-1021 were reported from Cinachyrella sp., 403 while a Haliclona yielded three new 3-alkylpyridinium alkaloids 1022-1024. 420 New manzamine-type alkaloids appeared in three separate reports 1025-1032 from Acanthostrongylophora, Amphimedon and Lissodendoryx sponges.…”

Redox signaling and Alzheimer’s disease: from pathomechanism insights to biomarker discovery and therapy strategy

“…An expected anti-inflammatory property of anthranilic acid is rooted in the fact that anthranilic acid is a precursor of some anti-inflammatory drugs as exemplified by mefenamic acid [64]. Additionally, Kwon et al revealed that oscarellin, a new anthranilic acid derivative isolated from a Philippine sponge, could diminish pro-inflammatory cytokines such as extracellular ERK1/2 and nuclear factor-κB (NF-κB), while anti-inflammatory cytokine of transcription factor-3 was enhanced, indicating anthranilic acid may also attenuate inflammation via modulating inflammatory cytokines [65]. As such, considering the prominent role of inflammation and oxidative stress in cognitive dysfunction, anthranilic acid might be a potential therapeutic target to fight against AD.…”

Marine Pharmacology in 2016–2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…SANK 71903 that blocked the binding of LPS to the cluster of differentiation 14 (CD14) in vitro and decreased TNF-α release by human U937 monocytic cells, concluding that these peptides could be developed for use "as anti-LPS drugs against LPS-associated diseases" [182]. Kwon and colleagues reported a new anthranilic acid derivative oscarellin (158) isolated from a Philippine sponge Oscarella stillans that strongly inhibited LPS-induced TNF-αand IL-6 production in murine macrophage RAW 264.7 macrophages by a mechanism "associated with inactivation of c-Jun NH 2 -terminal kinase (JNK), extracellular signal-regulated kinase (ERK), activator protein-1 (AP-1), and NF-κB and activation of activating transcription factor-3 (ATF-3)" [183]. Kim and colleagues observed that the novel alkaloid pseudane-VII (159) isolated from the marine bacterium Pseudolateromonas sp.…”