Diterpenes inhibiting NO production from Euphorbia helioscopia
Graphical abstract
Introduction
Euphorbia helioscopia L., belonging to the family Euphorbiaceae, is widely distributed in mainland China [1]. The whole plants of E. helioscopia, a traditional Chinese medicine in China, have been used for the treatment of malaria, bacillary dysentery, and osteomyelitis [1], [2]. Previous phytochemical investigations on E. helioscopia led to the isolation and identification of diterpenes, especially jatrophane-type diterpenes [3], [4], [5], [6], [7], [8], which showed cytotoxic activities [4], [5]. Though the chemistry and biological activities have been investigated, there have been no reports on the inhibitory effects of NO production of the chemical constituents or the extract from E. helioscopia. In our search for pharmacologically active substances in medicinal plants [9], [10], [11], much attention has been given to the occurrence of compounds with inhibitory effects of NO production, since NO plays an important role in the inflammatory process, and an inhibitor of NO production may be considered as a potential anti-inflammatory agent [12]. As a continuation of our search for inhibitors of NO production from plants, we investigated the chemical constituents of E. helioscopia. The phytochemical investigation led to the isolation of three new (1–3) and one unreported spectroscopic data (4) jatrophane diterpenenes, and nine known diterpenes (5–13) (Fig. 1). On the basis of detailed spectroscopic and spectrometric analyses (IR, ESIMS, HR-ESIMS, and 1D and 2D NMR) and X-ray crystallography, compounds 1–4 were elucidated and named euphorbiapenes A–D, and compounds 5–13 were characterized as euphoscopin F (5) [4], euphoscopin H (6) [8], euphoheliosnoid A (7) [7], euphoscopin C (8) [4], euphornin G (9) [8], 15-O-Acetyl-3-O-benzoylcharaciol (10) [13], ingenol monoacetate (11) [14], helioscopinolide A (12) [15], and helioscopinolide E (13) [15]. This paper herein describes the isolation and structure elucidation of these diterpenes and their inhibitory activities on lipopolysaccharide (LPS)-induced NO production in murine microglial BV-2 cells.
Section snippets
General
Melting points were determined with an XT-4 microscopic thermometer. The optical rotations were measured in MeOH, using an Autopal IV automatic polarimeter made by Autopal Industries Limited Company. The IR spectra were taken on a Bio-Rad FTS 6000 Fourier transform infrared (FTIR) spectrometer with KBr disks. The ESIMS spectra were obtained on a LCQ-Advantage mass spectrometer made by Finnigan Company (America). HR-ESIMS spectra were recorded by IonSpec 7.0 T FTICR MS (IonSpec Co., Ltd., Lake
Results and discussion
Compound 1 was obtained as colorless small quadrate crystals. Its molecular formula was determined as C31H38O7 from its HR-ESIMS (m/z 545.2513 [M + Na]+, calcd. for C31H38O7Na, 545.2515), which was compatible with the NMR data. The 1H NMR spectrum for 1 exhibited seven methyl signals [δH 1.06 (3H, d, J = 7.0 Hz, H3-16), 1.75 (3H, s, H3-17), 1.32 (3H, s, H3-18), 1.15 (3H, s, H3-19), 0.92 (3H, d, J = 6.9 Hz, H3-20), 2.19 (3H, s, OAc-14), and 2.20 (3H, s, OAc-15)] (Table 1), five olefinic protons [δH 5.72
Acknowledgments
The project was supported by the National Natural Science Foundation of China (No. 81102331).
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