Wedelolactone from Vietnamese <i>Eclipta prostrata </i>(L.) L. protected zymosan-induced shock in mice

Abstract

Wedelolactone is known to have biological activities such as anti-inflammation hepatitis, anti-hepatotoxic activity, and trypsin inhibitory effect. However, up to date, there has not been studied deeply in the role of wedelolactone for zymosan-induced signaling pathways in the process of regulating the excessive inflammatory responses in host. Here, we demonstrated that wedelolactone plays an essential role for regulation of zymosan-induced inflammatory responses in murine bone marrow-derived macrophages (BMDMs). The zymosan-mediated secretion of tumor necrosis factor-α (TNF)-α), interleukin (IL)-6), and IL12p40 but not IL-10 in BMDMs was significantly inhibited by pre-treatment with wedelolactone (30 µg/ml, P < 0.001). Furthermore, zymosan-induced supreoxide generation, NADPH oxidase (P < 0.001), phosphorylation of p47phox in BMDMs were significantly reduced by pre-treatment of wedelolactone (30 µg/ml). Collectively, these data indicated that wedelolactone reduced zymosan-induced inflammatory responses. Moreover, in vivo wedelolactone (30 mg/kg) significantly rescued from zymosan-induced shock through inhibition of systemic inflammatory cytokine levels.