Abstract
BackgroundIn the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1–4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA).ResultsThe methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ± 0.01 to 26.19 ± 0.64 μg/mL. Four highly pure steroid derivatives (1–4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S) 5α-cholestane-3β,4β,6α,7α,8β,15α,16β,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 μM), and for (25S) 5α-cholestane-3β,6α,8β,15α,16β,26-hexol (1) and (25S) 5α-cholestane-3β,6α,7α,8β,15α,16β,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ± 0.00 and 1.02 ± 0.01 μM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production.ConclusionThis is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases.
Highlights
In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1–4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and tumor necrosis factor (TNF)-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA)
As part of our ongoing investigations of Vietnamese marine organisms regarding anti-inflammatory activity [26,27,28,29,30,31], we found that a methanolic extract and dichloromethane fraction of P. nodosus showed significant in vitro anti-inflammatory effects
Activated BMDCs perform crucial functions in immune and inflammatory responses via the pathogen-associated molecular patterns (PAMPs)-stimulated production of pro-inflammatory cytokines such as IL-12 p40, IL-6, and TNF-α, which are involved in the pathogenesis of cardiovascular and neurodegenerational diseases and cancers through a series of cytokine signaling pathways
Summary
We examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1–4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA). Inflammation is one of the earliest innate immune responses to tissue injury and various pathological stimuli. It is a critical early factor in wound healing. Inflammation, which represents part of the complex biological response of vascular tissue to harmful exogenous harmful stimuli, is mediated by a variety of soluble factors, including a group of secreted polypeptides known as cytokines, which play key roles in the modulation of immune responses [3]. Interleukin (IL)-12 is a pro-inflammatory cytokine produced by activated antigen-presenting cells, dendritic cells, TNF has since been implicated in diverse inflammatory, infectious, and malignant conditions, and the importance of TNF in inflammation was demonstrated by the efficacy of anti-TNF antibodies or the administration of soluble TNF receptors (TNFRs) in controlling rheumatoid arthritis and other inflammatory conditions [10,11]. TNF is not typically detectable in healthy individuals, but serum
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