Journal Article

Anti-Inflammatory Effects of 5α,8α-Epidioxycholest-6-en-3β-ol, a Steroidal Endoperoxide Isolated from Aplysia depilans, Based on Bioguided Fractionation and NMR Analysis

Pereira, David M., Silva, Olga, Valentão, Patrícia, Videira, Romeu A., Andrade, Paula B., Jiménez, Carlos, Pereira, Renato B., Rodríguez, Jaime, Nieto, Rosa M.

2019

Overview

Sea hares of Aplysia genus are recognized as a source of a diverse range of metabolites. 5α,8α-Endoperoxides belong to a group of oxidized sterols commonly found in marine organisms and display several bioactivities, including antimicrobial, anti-tumor, and immunomodulatory properties. Herein we report the isolation of 5α,8α-epidioxycholest-6-en-3β-ol (EnP(5,8)) from Aplysia depilans Gmelin, based on bioguided fractionation and nuclear magnetic resonance (NMR) analysis, as well as the first disclosure of its anti-inflammatory properties. EnP(5,8) revealed capacity to decrease cellular nitric oxide (NO) levels in RAW 264.7 macrophages treated with lipopolysaccharide (LPS) by downregulation of the Nos2 (inducible nitric oxide synthase, iNOS) gene. Moreover, EnP(5,8) also inhibited the LPS-induced expression of cyclooxygenase-2 (COX-2), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) at the mRNA and protein levels. Mild selective inhibition of COX-2 enzyme activity was also evidenced. Our findings provide evidence of EnP(5,8) as a potential lead drug molecule for the development of new anti-inflammatory agents.

• Publisher: MDPI AG,MDPI
• Subject: 5α,8α-epidioxycholest-6-en-3β-ol / Adjuvants, Immunologic - pharmacology / Animals / anti-inflammatory activity / Anti-inflammatory agents / Anti-Inflammatory Agents - chemistry / Anti-Inflammatory Agents - isolation & purification / Anti-Inflammatory Agents - pharmacology / Anticancer properties / Aplysia / Aplysia - chemistry / Aplysia depilans / aquatic organisms / Chemical Fractionation / Cholesterol Esters - chemistry / Cholesterol Esters - isolation & purification / Cholesterol Esters - pharmacology / COX-1 / COX-2 / Cyclooxygenase-2 / Cytotoxicity / Down-Regulation - drug effects / Enzymatic activity / Enzyme Activation - drug effects / Enzyme activity / Ergosterol - analogs & derivatives / Ergosterol - chemistry / Ergosterol - isolation & purification / Ergosterol - pharmacology / Fractionation / Gene expression / gene expression regulation / genes / IL-6 / Immunomodulation / inducible nitric oxide synthase / Inflammation / iNOS / Interleukin 6 / Lead / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Macrophages / Macrophages - drug effects / Magnetic Resonance Spectroscopy / Marine molluscs / Marine organisms / messenger RNA / Metabolites / Mice / mRNA / Necrosis / Neoplasms / Nitric oxide / Nitric Oxide Synthase Type II - genetics / Nitric-oxide synthase / NMR / Nuclear magnetic resonance / nuclear magnetic resonance spectroscopy / oxidation / Physiology / Properties / prostaglandin synthase / protein content / RAW 264.7 Cells / Sterols / TNF-α / tumor necrosis factor-alpha / Tumor necrosis factor-α / Tumors