A new cerebroside from cordyceps militaris with anti-PTP1B activity.

Cordyceps militaris (L.) Link (C. militaris) has been used as a folk medicine for treatment of various diseases in China and some other countries. Recent evidence suggests that aqueous extracts of C. militaris have hypoglycemic activity. So the aim of this study was to isolate and characterize compounds with aiti-PTP1B (protein tyrosine phosphatase 1B) activity from C. militaris. As a result, cordycerebroside B (1) together with other three known cerebrosides (2-4) and a disaccharide (5) were isolated by silica gel column chromatography and semi-preparative high performance liquid chromatography (HPLC) and then elucidated on the basis of 1D and 2D nuclear magnetic resonance (NMR) spectroscopy, mass spectroscopy (MS) and chemical method. Among of which, cordycerebroside B was a new compound and isolated from C. militaris for the first time. The results of the activity assays demonstrated that all these four cerebrosides (compounds 1-4) showed marked inhibition activity against PTP1B with IC50 values of 4.68 ±â€¯0.18, 16.93 ±â€¯1.08, 10.43 ±â€¯0.64 and 18.92 ±â€¯1.65 µM. All the compounds had no discernible cytotoxicity for Rat pheochromocytoma (PC12 cells). These findings suggested that C. militaris or its cerebrosides may be considered as potential useful therapeutic agents for type 2 diabetes.

A Sphingosine-type cerebroside in Clavicorona pyxidata induce fruit body formation.

Clavicorona pyxidata is a wild edible and medicinal mushroom that is rich in bioactive natural products and has thus been extensively used as traditional medicine in China. The present study has determined that the organic crude extract prepared from a fermented culture of C. pyxidata imparted auto-inhibitory effects on mycelial growth and then induced the formation of fruiting bodies. By monitoring bioactivity, one compound was isolated via successive chromatography over silica gel, Sephadex LH-20, and Cl8-reversed phase silica gel and was identified as a known sphingosine-type cerebroside by nuclear magnetic resonance (NMR) and physicochemical data, namely, (4E, 8E)-N-D-2'-hydroxypalmitoyl-1-O-ß-D-glucopyranosyl-9-methyl-4,8-sphingadienine. The application of this cerebroside at a concentration of 200 µg/disc paper resulted in the inhibition of aerial hyphal growth of C. pyxidata. The findings of the present study indicated that this C. pyxidata cerebroside is a fruiting body-inducing substance (FIS).

Anti-inflammatory Cerebrosides from Cultivated Cordyceps militaris.

Cordyceps militaris (bei-chong-chaw, northern worm grass) is a precious and edible entomopathogenic fungus, which is widely used in traditional Chinese medicine (TCM) as a general booster for the nervous system, metabolism, and immunity. Saccharides, nucleosides, mannitol, and sterols were isolated from this fungus. The biological activity of C. militaris was attributed to the saccharide and nucleoside contents. In this study, the aqueous methanolic fraction of C. militaris fruiting bodies exhibited a significant anti-inflammatory activity. Bioactivity-guided fractionation of the active fraction led to the isolation of eight compounds, including one new and two known cerebrosides (ceramide derivatives), two nucleosides, and three sterols. Cordycerebroside A (1), the new cerebroside, along with soyacerebroside I (2) and glucocerebroside (3) inhibited the accumulation of pro-inflammatory iNOS protein and reduced the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophages. This is the first study on the isolation of cerebrosides with anti-inflammatory activity from this TCM.

A new cerebroside from the fruiting bodies of Hericium erinaceus and its applicability to cancer treatment.

A new cerebroside, cerebroside E (1) was isolated from the fruiting bodies of Hericium erinaceus (Hericiaceae). The structure of 1 was elucidated by a combination of extensive spectroscopic analyses, including extensive 2D NMR, HR-MS, and chemical reactions. Compound 1 was evaluated for its applicability to medicinal use in several human diseases using cell-based assays. As a result, compound 1 attenuated cisplatin-induced nephrotoxicity in LLC-PK1 cells and exhibited a significant inhibitory effect on angiogenesis in HUVECs. These results collectively reflect the beneficial effects of compound 1 in cancer treatment.

Structure-activity relationship of Baifuzi-cerebrosides on BKCa channel activation.

Our previous study reported that a mixture of cerebrosides from traditional Chinese medicine Baifuzi could activate BKCa channel. It is curious to know the effect of each single cerebroside on the channel. Here we isolated 5 pure cerebrosides from the mixture and determined their chemical structures. The most potent one increased the single channel open probability 6 folds with EC50 value of 1.0 µM. The structure-activity relationship revealed that acyl chain length of cerebrosides has potent effect, while configuration of double bond at C8-C9 on their long chain base has weak effect on the channel activity. Thus, this research provides a guide for design and synthesis of a lead cerebroside with more potent effect on the BKCa channel.

Two cerebrosides isolated from the seeds of Sterculia lychnophora and their neuroprotective effect.

Two cerebrosides named 1-O-b-D-glucopyranosyl-(2S,3R,4E,8Z)-2-[(2-hydroxyoctadecanoyl)amido]-4,8-octadecadiene-1,3-diol (1) and soya-cerebroside I (2) were isolated from the seeds of Sterculia lychnophora for the first time. Their structures were completely characterized by spectroscopic methods including IR, MS and NMR. Compound 1 exhibited moderate neuroprotective effect against SH-SY5Y cell damage induced by hydrogen peroxide.

Cerebroside and ceramide from the pollen of Brassica napus L.

The new cerebroside 1-O-(ß-D-glucopyranosyl)-(2S, 3S, 4R, 8E)-2-[(2'R)-2'-hydroxytetracosenoilamino]-8-octadecene-1,3,4-triol (1) and ceramide (2S, 3S, 4R, 8E)-2-[(2'R)-2'-hydroxytetracosenoilamino]-8-octadecene-1,3,4-triol (2) were isolated from the ethyl acetate extract of the pollen of Brassica napus L. The structures of 1 and 2 were elucidated on the basis of chemical and spectroscopic method. Two new compounds were evaluated for activity in vitro assays for the cytotoxic activities against human tongue squamous carcinoma cell line (Tca8113).

Glycocerebroside bearing a novel long-chain base from Sagina japonica (Caryophyllaceae).

A new glycocerebroside (1), along with one reported one (2), was isolated from the ethanol extract of Sagina japonica (Caryophyllaceae) and was fully characterized. The structures of two compounds were identified as (2S, 3S, 4R, 8E)-1-(beta-D-glucopyranosyl-3, 4-dihydroxy-2-[(R)-2'- hydroxypalmitoyl]amino-8-heptadecaene (1) and (2S, 3R, 8E)-1-(beta-D-glucopyranosyl-3-hydroxy-2-[(R)-2'-hydroxypalmitoyl]amino-8-octadecaene (2) by using spectroscopic methods ((1)H, (13)C, and 2D NMR, MS) and chemical degradation.

Cerebrosides with antiproliferative activity from Euphorbia peplis L.

Two new cerebrosides have been isolated from the whole plants of Euphorbia peplis L. The structures were established by FT-IR spectroscopy, FAB MS, EI-MS, ESI-MS, 1D and 2D NMR spectroscopy. The structures of the cerebrosides were characterized as 1-O-beta-d-glycosides of phytosphingosines, which comprised a common long-chain base, (2S, 3S, 4R, 8Z)-2-amino-8 (Z)-octadecene-1,3,4-triol with 2-hydroxy fatty acids of varying chain lengths (C25, C22) linked to the amino group. The isolated compounds were shown to possess significant antiproliferative properties against cultured human tumor cell lines KB and IMR-32.

Two new cerebrosides from the pollen of Typha angustifolia.

Two new cerebrosides, 1-O-(beta-d-glucopyranosyloxy)-(2S,3S,4R,8Z)-2-[(2'R)-2'-hydroxytricosanoylamino]-8-nonadecene-3,4-diol (1) and 1-O-(beta-D-glucopyranosyloxy)-(2S,3R,4E,8Z)-2-[(2'R)-2'-hydroxynonadecanoylamino]-4,13-nonadecene-3-diol (2), were isolated from the pollen of Typha angustifolia. Their structures were elucidated by chemical and spectral means. This is the first report on the occurrence of cerebroside in Typha (Typhaceae). Compounds 1 and 2 exhibited effect on the proliferation of cultured vascular smooth muscle cell (VSMCs) induced by fatal bovine serum (FBS).

An isomeric mixture of novel cerebrosides isolated from Impatiens pritzellii reduces lipopolysaccharide-induced release of IL-18 from human peripheral blood mononuclear cells.

An isomeric mixture of two cerebrosides, soya-cerebrosides I and II, was isolated from an ethno drug, the rhizomes of Impatiens pritzellii Hook. f. var. hupehensis Hook. f., and their structures were identified by spectroscopic (NMR, MS) analysis. In order to determine the immunomodulatory activities of soya-cerebrosides I and II, the effects of the mixture of cerebrosides (MC) on cytotoxicity of human peripheral blood mononuclear cells (PBMC) and the inhibitory activities to lipopolysaccharide (LPS)-induced interleukin (IL)-18 in PBMC were studied. The MC at concentrations of 10 and 1 microM, without toxicity to PBMC in 24 h, showed obvious inhibitory activity on IL-18 secretion. Because of this effect of modulating the cellular immune response, soya-cerebrosides I and II were considered to be the active substances of this ethno drug.

A new cerebroside from Gynura divaricata.

A new cerebroside, 1-O-beta-D-glucopyranosyl-(2S,3S,4R,10E)-2-[(2'R)-2'-hydroxyltricosanoyl-amino]-10-octadecene-1,3,4-triol was isolated from the aerial parts of Gynura divaricata DC.

[Studies on chemical constituents in seeds of Cicer arietinum].

OBJECTIVE: To study the chemical constituents in seeds of Cicer arietinum, so that to find bioactive natural products. METHOD: Dried and sprouted seeds of C. arietinum were extracted with ethanol of various concentrations respectively, then isolated and purified by silica gel, macroreticular resin D 101, Sephadex LH -20 gel column chromatography, and structures of compounds were identified by spectral analysis. RESULT: Nine compounds have been isolated and identified: 3-hydroxy-olean-12-ene (1), biochanin A-7-O-beta-D-glucoside (2), cerebroside (3), 1-ethyl-alpha-L-galactoside (4), uridine (5), adenosine (6), trytophan (7), biochanin A (8), fomononetin (9). CONCLUSION: Compounds 1, 3, 4, 6, 7 were isolated from genus Cicer for the first time.

[Chemical study on fruiting bodies of Boletus vioaceo-fuscus].

OBJECTIVE: To investigate the chemical constituents of Boletus vioaceo-fuscus. METHOD: The compounds were isolated with column chromatography. The structures were determined by spectroscopic techniques. RESULT: Six compounds were isolated from the fruiting bodies of Boletus vioaceo-fiuscus. They were identified as ergosta-5, 7, 22-triene-3beta-ol (1), dihydrofuran-2, 5-dione (2), (22E, 24R)-5alpha, 6alpha-epoxyergosta-8, 22-diene-3beta, 7alpha-diol (3), (22E, 24R)-5alpha, 6alpha-epoxyergosta-8 (14), 22-diene-3beta, 7alphadiol (4), cerebroside B (5) and adenosine (6), respectively. CONCLUSION: All the Compounds were obtained from the fruiting bodies of Boletus vioaceo-fiscus for the first time.

Constituents of Ocimum sanctum with antistress activity.

Three new compounds, ocimumosides A (1) and B (2) and ocimarin (3), were isolated from an extract of the leaves of holy basil (Ocimum sanctum), together with eight known substances, apigenin, apigenin-7-O-beta-D-glucopyranoside, apigenin-7-O-beta-D-glucuronic acid ( 4), apigenin-7- O-beta- d-glucuronic acid 6''-methyl ester, luteolin-7-O-beta-D-glucuronic acid 6''-methyl ester, luteolin-7-O-beta-D-glucopyranoside, luteolin-5-O-beta-D-glucopyranoside, and 4-allyl-1-O-beta-D-glucopyronosyl-2-hydroxybenzene (5), and two known cerebrosides. The structures of the new compounds were determined on the basis of extensive 1D and 2D NMR spectroscopic analysis. The new compounds (1- 3) and the known compounds 4 and 5 were screened at a dose of 40 mg/kg body weight for acute stress-induced biochemical changes in male Sprague-Dawley rats. Compound 1 displayed promising antistress effects by normalizing hyperglycemia, plasma corticosterone, plasma creatine kinase, and adrenal hypertrophy. Compounds 2 and 5 were also effective in normalizing most of these stress parameters. In contrast, compounds 3 and 4 were ineffective in normalizing any of these effects.

[Chemical constituents from root of Psammosilene tunicoides].

OBJECTIVE: To investigate the chemical constituents from the root of Psammosilene tunicoides. METHOD: Column chromatographic methods were used to isolate the chemical constituents of this plant. ESI-MS, EI-MS and NMR methods were employed for their structural elucidation. RESULT: Seven compounds were isolated and identified as goyaprosaponin (1), Soya-cerebroside (2), tectoridin (3), alpha-spinasterol (4), tetracosanoic acid (5), beta-sitosterol (6), daucosterol (7) respectively. CONCLUSION: Compounds 2-7 were obtained from genus Psammosilene for the first time.

Cerebrosides and tocopherol trimers from the seeds of Euryale ferox.

Two new cerebrosides, ferocerebrosides A (1) [(2S,3R,4E,8E,2'R)-1-O-(beta-glucopyranosyl)-N-(2'-hydroxydocosanoyl)-4,8-sphingadienine] and B (2) [(2S,3R,4E,8E,2'R)-1-O-(beta-glucopyranosyl)-N-(2'-hydroxytetracosanoyl)-4,8-sphingadienine], two new tocopherol trimers, ferotocotrimers C (5) and D (6), and two known tocopherol trimers, IVb (3) and IVa (4), were isolated from the seeds of Euryale ferox. Their structures were determined on the basis of spectroscopic data, especially 1D and 2D NMR experiments. Compounds 1 and 2 showed cytotoxicity in the brine shrimp lethality bioassay, with LC50 values of 0.17 and 0.20 mM, respectively.

[New cerebroside from leaves of pineapple].

OBJECTIVE: To study the chemical constituents of the leaves of pineapple. METHOD: Chromatographic methods were used to isolate compounds from the leaves of pineapple and spectral methods were used to identify the structures of the isolated compounds. RESULT: Compound 1 was isolated from the leaves of pineapple. It was identified as 1-O-beta-D-glucopyranosyl-(2S, 3R, 4E, 11E)-2-[(2(R)-hydroxydocosanoyl) amido]-4, 11-hexadecanediene-1, 3-diol. CONCLUSION: Compound 1 was a new compound.

[Chemical constituents from flos Sesamum indicum L].

Sesame (Sesamum indicum L. ) belongs to Pedaliaceae, and its dry flowers have been used to cure alopecia, frostbite and constipation as a Traditional Chinese Medicine. Interestingly, the Flos Sesamum indicum L. was usually used to cure verruca vulgaris and verruca plana in folk of China, and showed a pleasant result. Previous chemical investigations of this plant mainly concentrate on its seeds, showed the presence of proteins and fat oils, herein we make a systematic chemical research on the dry flowers of this plant. Column chromatography including silica gel, C18 and Sephadex LH-20 were used to separate the chemical constituents and the structures were determined by chemical and spectroscopic methods. Ten compounds were isolated from the 95% ethanol extract of the plant and elucidated as latifonin (1), momor-cerebroside (2), soya-cerebroside II (3), 1-O-beta-D-glucopyranosyl-(2S, 3S, 4R, 5E,9Z)-2-N-(2'-hydroxytetracosanoyl) 1,3,4-trihydroxy-5,9-octadienine (4), 1-O-beta-D-glucopyranosyl-(2S, 3S, 4R, 8Z)-2-N-(2' R) 2'-hydroxytetracosanoyl) 3,4-dihydroxy-8-octadene (5), (2S, 1" S) -aurantiamide acetate (6), benzyl alcohol-O-(2'-O-beta-D-xylopyranosyl, 3'-O-beta-D-glucopyranoside)-beta-D-glucopyranoside (7), beta-sitosterol (8), daucosterol (9) and D-galacititol (10). Among them, 4 is a new compound, and others were isolated from the flowers of the plant for the first time. Compounds 2 to 4 belong to cerebroside, which is rare to be found in land plants and was proved to possess many bioactivities.

A new cerebroside from Uvaria tonkinensis var. subglabra.

A new cerebroside, subglain A (1), together with five known compounds (2-6) have been isolated from the stems of Uvaria tonkinensis var. subglabra. The structure of 1 has been determined to be 1-O-beta-D-glucopyranosyl-(2S,3S,4R,8Z,2'R)-2-[N-(2'-hydroxytetracosanyl)-N-(1'',2''-dihydroxyethyl)-amide]-8-tetradecene-1,3,4-triol by spectroscopic evidence. The known compounds were identified as schisandriside (2), erythritol (3), beta-D-glucopyranose (4), kaempferol-3,7-O-alpha-L-dirhamnoside (5), and (+)-lyoniresinol (6).