Immunomodulatory and Anti-Inflammatory Activity of Selected Osthole Derivatives

Abstract

From osthole [7-methoxy-8-(3-methyl-but-2-enyl)-chromen-2-one] (I), obtained by selective extraction of Peucedanum ostruthium (L.) W. Koch roots, ostholic acid (II) was synthetized as a result of its oxidation with chromium trioxide. From ostholic acid, through its chloride, four amides were obtained: the morpholide 1, the p-chloro-benzylamide 2, the piperidine 3 and the N-methyl-piperazide 4. Except for 1, other compounds have not been described before. The amides 1 -4 and their precursor osthole (I) were tested for their potential activities in selected immunological assays. The compounds showed moderate inhibitory activity in the humoral immune response to sheep erythrocytes in mice in vitro, and 4 was the most suppressive. The effects of 1 and 3 on concanavalin A-and pokeweed mitogen-induced mouse splenocyte proliferation were inhibitory and those of 4 stimulatory. The compounds were also tested for their activity on tumour necrosis factor α and interleukin 6 production, induced by lipopolysaccharide, in cultures of rat peritoneal cells and human peripheral blood mononuclear cells. Compounds 1, 3 and 4 inhibited tumour necrosis factor α (rat cells), whereas compound 2 stimulated the production of both cytokines. Compounds 1, 2 and 3 were also strongly inhibitory on tumour necrosis factor α production in human blood cells (73, 78 and 80% inhibition at 10 μg/ml, respectively). On the other hand, 2 and 4 stimulated the interleukin 6 production (2-to 3-fold stimulation). In addition, 2 and 4 suppressed the carrageenan-induced infl ammation in mice (56.5% and 68.3% inhibition, respectively). In summary, the compounds predominantly displayed suppressive and antiinfl ammatory activities in the investigated models.

Osthole activates glucose uptake but blocks full activation in L929 fibroblast cells, and inhibits uptake in HCLE cells

“…Osthole exerts a wide range of biological effects including antiosteoporotic (Zhang, et al 2007, Ming, et al 2011, Tang, et al 2010) anti-inflammatory (Zimecki, et al 2009), antiseizure (Luszczki, et al 2009), antiallergic (Matsuda, et al 2002), and anti-fatty liver activities (Zhang, et al 2007, Sun, et al 2009). However, the bulk of studies have reported on osthole’s effects on cell growth, its proapoptotic effects and its potential as an anticancer or antitumor agent (Lopez-Gonzalez, et al 2004, Riviere, et al 2006, Xu, et al 2011, Yang, et al 2010, Hung, et al 2011, Zhang, et al 2012).…”

Fluorescence quenching of osthole by silver nanoparticles

“…But, to the best of our knowledge, fluorescence quenching of osthole by silver nanoparticles has not been examined previously. As a simple coumarin compound, osthole is one of the important components of the Chinese medicine angelica, which is often used for lowering blood pressure, improving neurobehavioral functions, and inhibiting bacterial growth [22][23][24][25]. The structural formula of osthole is shown in Fig.…”

Main constituents from the seeds of VietnameseCnidium monnieriand cytotoxic activity

“…Osthole (1) has been converted into its derivatives by several reactions, for instance, oxidation with chromium trioxide, and some of its derivatives showed valuable immunomodulatory and anti-inflammatory activities (Zimecki et al, 2009). In this case, we obtained a large amount of osthole (1) which allowed us to make its derivative, compound 5, by one pot reaction with a good yield (80%).…”