Inotodiol From Inonotus obliquus Chaga Mushroom Induces Atypical Maturation in Dendritic Cells.

Dendritic cells (DCs) have the ability to stimulate naïve T cells that coordinate subsequent adaptive response toward an inflammatory response or tolerance depending on the DC differentiation level. Inotodiol, a lanostane triterpenoid found in Inonotus obliquus (wild Chaga mushroom), is a natural compound with a wide range of biological activities. In this study, we investigated whether inotodiol promotes the maturation of bone marrow-derived DCs (BMDCs) and inotodiol-treated BMDCs induce T cell activation. Inotodiol increased the expression of surface maturation markers, including MHC-I, MHC-II, CD86, and CD40, on BMDCs without affecting the production of various cytokines, including TNF-α and IL-12p40 in these cells. T cells primed with inotodiol-treated BMDCs proliferated and produced IL-2, without producing other cytokines, including IL-12p40 and IFN-γ. Injection of inotodiol into mice induced maturation of splenic DCs and IL-2 production, and the administration of inotodiol and inotodiol-treated BMDCs induced the proliferation of adoptively transferred CD8+ T cells in vivo. The phosphatidylinositol-3-kinase inhibitor wortmannin abrogated the upregulation of Akt phosphorylation and CD86 and MHC-II expression induced by inotodiol. However, inotodiol failed to induce phosphorylation of the IκB kinase and degradation of IκB-α, and increased expression of CD86 induced by inotodiol was not blocked by an IκB kinase inhibitor. These results suggest that inotodiol induces a characteristic type of maturation in DCs through phosphatidylinositol-3-kinase activation independent of NF-κB, and inotodiol-treated DCs enhance T cell proliferation and IL-2 secretion.

Structures of eremophilane-type sesquiterpene glucosides, alticolosides A-G, from the Far Eastern endemic Ligularia alticola Worosch.

Seven eremophilane-type sesquiterpene glucosides, alticolosides A-G, have been isolated from aerial parts of the endemic Far Eastern species Ligularia alticola Worosch. (Family Asteraceae) along with two known compounds, monoterpenoid glycoside (4S)-α-terpineol 8-O-ß-D-glucopyranoside and norditerpenoid glycoside 7(8)-dihydro-ß-ionone 3-O-ß-D-glucopyranoside. Alticoloside D was identified with the earlier known 8-O-(ß-D-glucopyranosyl)-2-oxo-eremophila-1(10),8,11-triene, but the stereostructure of the latter was revised on the basis of ROESY and CD data. All the glycosides are derivatives of new eremophilane-type aglycones, differing from known eremophilanes in details of planar and/or stereo structures except for the aglycone of alticoloside E.

Terpenoid metabolites from Spongia spp. and their effects on nucleic acid biosynthesis in sea urchin eggs.

19-Norspongia-13(16),14-diene-3-one (1) was isolated for the first time from a natural source, along with a series of known spongiane diterpenoids (2-11) and sesquiterpene (12) from two unidentified species belonging to the genus Spongia. The effects of 1, 4, 5, 8-12 on biosynthesis of nucleic acids and embryonic development of the sea urchin Strongylocentrotus intermedius have been studied. All the compounds inhibit sea urchin embryo development at concentration of 20 microg/mL and above and DNA biosynthesis at the dose of 10 microg/mL. The inhibitory effect of diterpenoids at least partly may be explained by the inhibition of thymidine kinase activity.

Spongian diterpenoids from the sponge Spongia (Heterofibria) sp.

Five new (1, 2, 4-6) and one known (3) diterpenoid were isolated from the keratose sponge Spongia (Heterofibria) sp. Structures of these compounds and their absolute configurations were proposed on the basis of X-ray analysis of 1, its CD spectrum, and NMR and MS spectroscopic studies of 1-6. One of the new diterpenoids was shown to be 2(R),3(S),4(S)-3,18-methylene-2-acetoxyspongia-13(16),14-diene (6), possessing a novel carbon skeleton system.

Isolation and structures of erylosides from the Carribean sponge Erylus goffrilleri.

Eight new triterpene glycosides, erylosides R ( 1), S ( 2), T ( 3), U ( 4), F 5-F 7 ( 5- 7), and V ( 8), were isolated from the sponge Erylus goffrilleri collected near Arresife-Seko Reef (Cuba). Structures of 1 and 2 were determined as the corresponding monosides having aglycons related to penasterol with additional oxidation and methylation patterns in their side chains. Eryloside T ( 3) was structurally identified as the Delta (7)-isomer of 1, containing an unusual (14-->9)-lactone ring in the tetracyclic aglycon moiety, and eryloside U ( 4) was shown to be the 7,8-epoxide of 3. Erylosides F 5-F 7 ( 5- 7) and V ( 8) contain new variants of carbohydrate chains with two ( 5- 7) and three ( 8) sugar units, respectively.

Mycalosides B-I, eight new spermostatic steroid oligoglycosides from the sponge Mycale laxissima.

New steroidal oligoglycosides mycalosides B-I (2-9) have been isolated from the polar extract of the Caribbean sponge Mycale laxissima, and their structures have been elucidated by 1D and 2D NMR ((1)H, (13)C, DEPT, COSY-45, COSY-RCT, HSQC, HMBC, and NOESY spectra) and MALDI-TOF mass spectrometry. Mycalosides B (2) and C (3) were shown to be 27- and 28-nor derivatives of the previously known tetraoside mycaloside A (1). Mycaloside D (4) differs from 1 only in the presence of an additional acetyl group in the carbohydrate moiety. Mycaloside E (5) was structurally identified as a 28-nor-4-dehydroxy derivative of 1. Mycalosides F-H (6-8), differing from each other by the structures of their side chains and nonacetylated (7, 8) or acetylated (6) tetrasaccharide carbohydrate moieties, have new 5(6)-unsaturated 3 beta,4 beta,21-trihydroxy-15-keto-steroidal aglycons. Mycaloside I (9) is a tetraoside of a new 7,24(28)-diunsaturated 3beta,15 beta,29-trihydroxystigmastane aglycon. It was established that the total fraction of the mycalosides as well as mycalosides A (1) and G (7) inhibit the fertilization of eggs by sperm of the sea urchin Strongylocentrotus nudus preincubated with these compounds.