New Ceramides and Cerebrosides from the Deep-Sea Far Eastern Starfish Ceramaster patagonicus.

Three new ceramides (1−3) and three new cerebrosides (4, 8, and 9), along with three previously known cerebrosides (ophidiocerebrosides C (5), D (6), and CE-3-2 (7)), were isolated from a deep-sea starfish species, the orange cookie starfish Ceramaster patagonicus. The structures of 1−4, 8, and 9 were determined by the NMR and ESIMS techniques and also through chemical transformations. Ceramides 1−3 contain iso-C21 or C23 Δ9-phytosphingosine as a long-chain base and have C16 or C17 (2R)-2-hydroxy-fatty acids of the normal type. Cerebroside 4 contains C22 Δ9-sphingosine anteiso-type as a long-chain base and (2R)-2-hydroxyheptadecanoic acid of the normal type, while compounds 8 and 9 contain saturated C-17 phytosphingosine anteiso-type as a long-chain base and differ from each other in the length of the polymethylene chain of (2R)-2-hydroxy-fatty acids of the normal type: C23 in 8 and C24 in 9. All the new cerebrosides (4, 8, and 9) have ß-D-glucopyranose as a monosaccharide residue. The composition of neutral sphingolipids from C. patagonicus was described for the first time. The investigated compounds 1−3, 5−7, and 9 exhibit slight to moderate cytotoxic activity against human cancer cells (HT-29, SK-MEL-28, and MDA-MB-231) and normal embryonic kidney cells HEK293. Compounds 2, 5, and 6 at a concentration of 20 µM inhibit colony formation of MDA-MB-231 cells by 68%, 54%, and 68%, respectively. The colony-inhibiting activity of compounds 2, 5, and 6 is comparable to the effect of doxorubicin, which reduces the number of colonies by 70% at the same concentration.

Holospiniferoside: A New Antitumor Cerebroside from The Red Sea Cucumber Holothuria spinifera: In Vitro and In Silico Studies.

Chemical investigation of the methanolic extract of the Red Sea cucumber Holothuria spinifera led to the isolation of a new cerebroside, holospiniferoside (1), together with thymidine (2), methyl-α-d-glucopyranoside (3), a new triacylglycerol (4), and cholesterol (5). Their chemical structures were established by NMR and mass spectrometric analysis, including gas chromatography-mass spectrometry (GC-MS) and high-resolution mass spectrometry (HRMS). All the isolated compounds are reported in this species for the first time. Moreover, compound 1 exhibited promising in vitro antiproliferative effect on the human breast cancer cell line (MCF-7) with IC50 of 20.6 µM compared to the IC50 of 15.3 µM for the drug cisplatin. To predict the possible mechanism underlying the cytotoxicity of compound 1, a docking study was performed to elucidate its binding interactions with the active site of the protein Mdm2-p53. Compound 1 displayed an apoptotic activity via strong interaction with the active site of the target protein. This study highlights the importance of marine natural products in the design of new anticancer agents.

Contortamide, a new anti-colon cancer cerebroside and other constituents from Tabernaemontana contorta Stapf (Apocynaceae).

A new cerebroside, Contortamide (1) together with nine known compounds spegatrine (2), affinisine (3), Nb-methylaffinisine (4), ursolic acid (5), α-amyrin (6), bauerenol acetate (7), lupeol (8), betulinic acid (9) and ß-sitosterolglycoside (10) were isolated from the trunk bark of Tabernaemontana contorta Stapf. The new compound 1 showed significant activity against Caco-2 colon cancer cells with the MTT method. Compounds 1-4 and 6-9 were isolated for the first time from this species.

New Cytotoxic Cerebrosides from the Red Sea Cucumber Holothuria spinifera Supported by In-Silico Studies.

Bioactivity-guided fractionation of a methanolic extract of the Red Sea cucumber Holothuria spinifera and LC-HRESIMS-assisted dereplication resulted in the isolation of four compounds, three new cerebrosides, spiniferosides A (1), B (2), and C (3), and cholesterol sulfate (4). The chemical structures of the isolated compounds were established on the basis of their 1D NMR and HRMS spectral data. Metabolic profiling of the H. spinifera extract indicated the presence of diverse secondary metabolites, mostly hydroxy fatty acids, diterpenes, triterpenes, and cerebrosides. The isolated compounds were tested for their in vitro cytotoxicities against the breast adenocarcinoma MCF-7 cell line. Compounds 1, 2, 3, and 4 displayed promising cytotoxic activities against MCF-7 cells, with IC50 values of 13.83, 8.13, 8.27, and 35.56 µM, respectively, compared to that of the standard drug doxorubicin (IC50 8.64 µM). Additionally, docking studies were performed for compounds 1, 2, 3, and 4 to elucidate their binding interactions with the active site of the SET protein, an inhibitor of protein phosphatase 2A (PP2A), which could explain their cytotoxic activity. This study highlights the important role of these metabolites in the defense mechanism of the sea cucumber against fouling organisms and the potential uses of these active molecules in the design of new anticancer agents.

New Cytotoxic Natural Products from the Red Sea Sponge Stylissa carteri.

Bioactivity-guided isolation supported by LC-HRESIMS metabolic profiling led to the isolation of two new compounds, a ceramide, stylissamide A (1), and a cerebroside, stylissoside A (2), from the methanol extract of the Red Sea sponge Stylissa carteri. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR and HRMS. The bioactive extract's metabolomic profiling showed the existence of various secondary metabolites, mainly oleanane-type saponins, phenolic diterpenes, and lupane triterpenes. The in vitro cytotoxic activity of the isolated compounds was tested against two human cancer cell lines, MCF-7 and HepG2. Both compounds, 1 and 2, displayed strong cytotoxicity against the MCF-7 cell line, with IC50 values at 21.1 ± 0.17 µM and 27.5 ± 0.18 µM, respectively. They likewise showed a promising activity against HepG2 with IC50 at 36.8 ± 0.16 µM for 1 and IC50 30.5 ± 0.23 µM for 2 compared to the standard drug cisplatin. Molecular docking experiments showed that 1 and 2 displayed high affinity to the SET protein and to inhibitor 2 of protein phosphatase 2A (I2PP2A), which could be a possible mechanism for their cytotoxic activity. This paper spreads light on the role of these metabolites in holding fouling organisms away from the outer surface of the sponge, and the potential use of these defensive molecules in the production of novel anticancer agents.

Compound Porcine Cerebroside and Ganglioside Injection (CPCGI) Attenuates Sevoflurane-Induced Nerve Cell Injury by Regulating the Phosphorylation of p38 MAP Kinase (p38MAPK)/Nuclear Factor kappa B (NF-κB) Pathway.

BACKGROUND Compound porcine cerebroside and ganglioside injection (CPCGI) has been widely applied in clinical practice in China to treat functional confusion caused by brain diseases. Sevoflurane, a frequently-used inhalational anesthetic, was discovered to have neurotoxicity that can cause neurological damage in patients. The present study was performed to investigate the protective effect of CPCGI on sevoflurane-induced nerve damage and to reveal the neuroprotective mechanisms of CPCGI. MATERIAL AND METHODS Firstly, the hippocampal neurons were separated from Sprague-Dawley embryonic rats, and were stimulated by 3% sevoflurane for different times (0, 2, 4, and 6 h). Then, cell viability and cell apoptosis were assessed by thiazolyl blue tetrazolium bromide (MTT) and flow cytometry (FCM), respectively. Western blot analysis was used to determine the apoptosis-related protein expression levels. RESULTS The results demonstrated that 3% sevoflurane significantly inhibited cell viability but induced cell apoptosis in neurons in a time-dependent manner. Treatment with 3% sevoflurane also promoted the Bax (B cell leukemia/lymphoma 2​ (Bcl2)-associated X protein) and cleaved caspase3 protein expressions, and suppressed Bcl-2 and pro-caspase3 expressions in hippocampal neurons. In addition, phosphorylated (p)-p38 and p-p65 expression and the ratio of p-p38/p38 and p-p65/p65 were upregulated in a time-dependent manner after 3% sevoflurane treatment. Further analysis indicated that all the effects of 3% sevoflurane on hippocampal neurons were reversed by CPCGI pre-treatment. CONCLUSIONS We demonstrated the neuroprotective role of CPCGI in sevoflurane-stimulated neuronal cell damage via regulation of the MAPK/NF-kappaB signaling pathway.

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.

Occurrence of Melibiose-Containing Glycosphingolipids in a Sample of a Sponge-Coral Association (Desmapsamma anchorata/Carijoa riisei).

In our research on biologically active compounds from Vietnamese marine invertebrates, rare melibiose-containing glycosphingolipids were found in a sample of a sponge-coral association (Desmapsamma anchorata/Carijoa riisei). Melibiosylceramides were analyzed as constituents of some multi-component RP-HPLC fractions, and the structures of 14 new (1b, 3b, 4a-4c, 6a-6c, 8b, 9a, 9b, 10b, 11a, 11b) and five known (2b, 5a-5c, 7b) natural compounds were elucidated using NMR, mass spectrometry, optical rotation, and chemical transformations. These α-d-Galp-(1→6)-ß-d-Glcp-(1 ↔ 1)-ceramides (presumably sponge-derived compounds) were shown to contain phytosphingosine-type n-t17:0 (1), (6E)-n-t17:1 (2), i-t17:0 (3), n-t18:0 (4), (6E)-n-t18:1 (5), i-t18:0 (6), (6E)-i-t18:1 (7), i-t19:0 (8), (6E)-i-t19:1 (9), ai-t19:0 (10), and (6E)-ai-t19:1 (11) backbones N-acylated with saturated straight-chain (2R)-2-hydroxy C21 (a), C22 (b), and C23 (c) acids. Characteristic trends in the fragmentations of the terminal parts of tetraacetylated normal-chain and iso- and anteiso-branched sphingoid bases were observed using GC/MS. The total sum of melibiosylceramides and compound 5b caused a reduction in colony formation of human melanoma cells.

The Protective Activities of Dietary Sea Cucumber Cerebrosides against Atherosclerosis through Regulating Inflammation and Cholesterol Metabolism in Male Mice.

SCOPE: Cerebroside is an active component extracted from sea cucumber (SCC), which is a traditional tonic food in China. In this study, the protective effect of SCC on atherogenesis is investigated and the possible underlying mechanism is determined. METHOD AND RESULTS: Male C57BL/6J obese mice were first used to explore the impact of SCC at different doses on alleviating lipid disorders and insulin sensitivity. Then ApoE-/- mice were used to evaluate the protective activities of SCC on atherosclerosis. The results demonstrated that dietary SCC increased the insulin sensitivity and reduced serum and hepatic lipid profiles in a dose-dependent manner in C57BL/6J mice. In ApoE-/- mice, SCC treatment significantly decreased the atherosclerotic lesion formation and attenuated inflammation by decreasing the levels of inflammatory cytokines, such as CRP, TNF-α, IL-6. Compared to the model group, the SCC group showed lower cholesterol levels in serum and liver by mediating the expression of genes related to hepatic LDL uptake and cholesterol excretion. CONCLUSION: Dietary SCC has the potential to eliminate atherosclerosis through regulating inflammation and cholesterol metabolism, and may be beneficial for the health of patients with cardiovascular disease.

Immunohistochemical expression of cereblon and MUM1 as potential predictive markers of response to lenalidomide in extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma).

Lenalidomide is an active agent for the treatment of MALT lymphoma. Recently, high expression levels of cereblon (CRBN) and MUM1 have been associated with better response rates in multiple myeloma treated with lenalidomide. However, there are no data on CRBN and MUM1 expression in MALT lymphoma. In the current study, we have systematically investigated a potential correlation of CRBN/MUM1 immunohistochemical expression and response to lenalidomide-based therapy in a series of 46 patients with MALT lymphoma treated at the Medical University Vienna 2009 to 2014. In total, 28% (13/46) of biopsy specimens derived from gastric tissues, while 72% (33/46) originated from extragastric MALT lymphoma. In terms of CRBN, 54% showed high expression (CRBN+, ≥50% positive cells); the remaining 46% were classified as low expression (CRBN-). In contrast to other reports, there was a non-significant trend towards worse response rates in CRBN+ (68% versus 86%, P = 0.161). Relapse rates (P = 0.592) and PFS (P = 0.306) did not differ between CRBN+/CRBN-, but all 3 patients progressing on lenalidomide were CRBN+ and both patients completely lacking CRBN expression responded to treatment. Concerning MUM1, 62% were MUM1-negative (MUM1-) and 38% positive (MUM1+). There was no difference in response to lenalidomide by MUM1-status (MUM1+ 71% versus MUM1- 79%, P = 0.546) and also relapse rates (P = 0.828) and PFS (P = 0.681) did not differ. Interestingly, a subgroup analysis of gastric lymphoma revealed a significantly better PFS for CRBN- and MUM1- patients, respectively (both P < 0.05). To conclude, there was no significant difference in response to lenalidomide between patients with low or high expression of CRBN/MUM1 in a general population of MALT lymphoma, and immunohistochemical CRBN/MUM1 assessment cannot be recommended in the clinical routine.

Neuroprotective Activity of Cerebrosides from Typhonium giganteum by Regulating Caspase-3 and Bax/Bcl-2 Signaling Pathways in PC12 Cells.

An investigation of the potential neuroprotective natural product constituents of the rhizomes of Typhonium giganteum led to the isolation of two new cerebrosides, typhonosides E (1) and F (2), along with 11 known analogues (3-13). The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. The activity of these compounds against glutamate-induced cell apoptosis was investigated in PC12 cells. All compounds exhibited such activity, which was related to the length of the fatty acyl chain. Among them, longan cerebroside II (11), with the longest fatty acyl chain, showed the most potent protective effect in PC12 cells from glutamate injury, with an EC50 value of 2.5 µM. Moreover, at the molecular level, longan cerebroside II (11) downregulated the expression of caspase-9, caspase-3, and Bax, upregulated the expression of Bcl-2, and decreased the level of cytosolic cytochrome c in a concentration-dependent manner.

Cerebrosides from Sea Cucumber Protect Against Oxidative Stress in SAMP8 Mice and PC12 Cells.

Alzheimer's disease (AD) is a neurodegenerative disorder. Emerging evidence implicates ß-amyloid (Aß) plays a critical role in the progression of AD. In this study, we investigated the protective effect of cerebrosides obtained from sea cucumber against senescence-accelerated mouse prone 8 (SAMP8) mice in vivo. We also studied the effect of cerebrosides on Aß-induced cytotoxicity on the rat pheochromocytoma cell (PC12) and the underlying molecular mechanisms. Cerebrosides ameliorated learning and memory deficits and the Aß accumulation in demented mice, decreased the content of malondialdehyde (MDA), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG), 8-hydroxy-2'-deoxyguanosine (8-oxo-G), and nitric oxide (NO), and enhanced the superoxide dismutase (SOD) activity significantly. The neuroprotective effect of sea cucumber cerebrosides (SCC) was also verified in vitro: the cerebrosides increased the survival rate of PC12 cells, recovered the cellular morphology, downregulated the protein levels of Caspase-9, cleaved Caspase-3, total Caspase-3, and Bax, and upregulated the protein level of Bcl-2, revealing that cerebrosides could inhibit Aß-induced cell apoptosis. The results showed the protective effect of SCC was regulated by the mitochondria-dependent apoptotic pathway. Our results provide a new approach to developing the marine organisms as functional foods for neuroprotection.

A new cerebroside and the cytotoxic constituents isolated from Xylaria allantoidea SWUF76.

A new cerebroside, namely allantoside (1), and 10 known compounds (2-11) were isolated from Xylaria allantoidea SWUF76. The structure of compound 1 was determined by comprehensive spectroscopic analysis including 1D and 2D nuclear magnetic resonance (NMR) as well as high-resolution electron ionisation mass spectrometry (HREIMS) and electrospray ionisation mass spectrometry (ESIMS). Compounds 1, 4, 5, 6, 7, 8 and 11 were evaluated for cytotoxic activities against cancer cell lines (Hela, HT29, HCT116 and MCF-7) and normal Vero cell lines by MTT assay. Compounds 6 and 7 exhibited anticancer activity after 24 h of treatment. Compound 7 showed significant cytotoxicity against Hela (IC50 = 2.24 µg/mL), HT29 (IC50 = 2.51 µg/mL), HCT116 (IC50 = 3.50 µg/mL) and MCF-7 (IC50 = 3.77 µg/mL) and Vero (IC50:3.65 µg/mL) cells. Compound 6 showed slight cytotoxicity against all tested cancer cell lines.

New Cerebroside and Nucleoside Derivatives from a Red Sea Strain of the Marine Cyanobacterium Moorea producens.

In the course of our ongoing efforts to identify marine-derived bioactive compounds, the marine cyanobacterium Moorea producens was investigated. The organic extract of the Red Sea cyanobacterium afforded one new cerebroside, mooreaside A (1), two new nucleoside derivatives, 3-acetyl-2'-deoxyuridine (2) and 3-phenylethyl-2'-deoxyuridine (3), along with the previously reported compounds thymidine (4) and 2,3-dihydroxypropyl heptacosanoate (5). The structures of the compounds were determined by different spectroscopic studies (UV, IR, 1D, 2D NMR, and HRESIMS), as well as comparison with the literature data. Compounds 1-5 showed variable cytotoxic activity against three cancer cell lines.

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.

Effects of portulacerebroside a on apoptosis of human leukemia HL60 cells and p38/JNK signaling pathway.

Acute myeloid leukemia is known as one of the most malignant diseases. We aimed at exploring the effect of portulacerebroside A (PCA) on the apoptosis in human leukemia HL60 cells and clarify the possible mechanisms involved in. By MTT analysis, we found that PCA (1-100 µM) inhibited the cell viability in a time- and dose-dependent manner, and cell cycle was arrested at G0/G1 period. PCA treatment from 5 to 50 µM dose-dependently induced apoptosis from 12.7 ± 1.56% to 52.7 ± 6.214% of HL60 cells. Mitochondrial membrane potential (MMP) was decreased and reactive oxygen species (ROS) accumulated obviously. mRNA expressions and protein levels of Bax/Bcl-2, caspase-3 and caspase-9 were elevated significantly. ERK1/2, JNK1/2 and p38 MAPK pathway were blocked detected by western blot analysis. In conclusion, PCA can act as a new agent for leucocythemia treatment.

Protective effects of cerebrosides from sea cucumber and starfish on the oxidative damage in PC12 cells.

Neurodegenerative disorders are a class of diseases that have been linked to apoptosis induced by elevated levels of reactive oxygen species (ROS). The present study was undertaken to explore the effect of sea cucumber cerebrosides (SCC) and starfish cerebrosides (SFC) on the hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP)-induced oxidative damage in PC12 cells. Cell viability, the leakage of lactate dehydrogenase (LDH), reactive oxygen species (ROS) level and superoxide dismutase (SOD) activity were determined for their effect on oxidative damage. Quantitative real-time PCR was investigated to analyze the mitochondrial genes expression. These results showed that both SCC and SFC decreased the leakage of LDH and intracellular ROS in a dose-dependent manner. SCC and SFC could also increase the SOD activity compared with the model groups. In H2O2 damage model, 400 µg/mL SCC increased the SOD activity by 79%, which was stronger than SFC. The results demonstrated that SCC and SFC exhibited the protective effects, which may be related to their antioxidant action. In addition, SCC and SFC dramatically increased the gene expression of B-cell lymphoma 2 (Bcl-2) but significantly decreased the gene expression of Cytochrome c, caspase9 and caspase3 compared with H2O2 or t-BHP treatment. These results suggested that SCC and SFC might exert a protective function against oxidative damage by inhibiting mitochondria-mediated apoptosis pathway. In conclusion, SCC and SFC played an important protective role in H2O2 and t-BHP-induced damage of PC12 cells, suggesting that the SCC and SFC may be a potential therapeutic agent against nervous system oxidative damage.

[Protective effects of cerebroside from sea cucumber on the oxidative damage of PC12 cells induced by H2O2].

OBJECTIVE: To study the protective effects of cerebroside from sea cucumber (SCC) on the oxidative damage of PC12 cells induced by H2O2. METHODS: An oxidative damage model of PC12 cells was induced by H2O2. The survival rate of the cells was determined by MTT method. The leakage of LDH into cell cultures was determined to evaluate the degree of cell damage. The generation of intracellular reactive oxygen species (ROS) was detected by using DCFH-DA fluorescent probe. The activity of total antioxidation capacity (T-AOC) was determined by chemical colorimetric method and the SOD activity was measured by xanthine oxide method. RESULTS: The injury of PC12 cells induced by H2O2 could be reduced obviously by SCC. Compared with the model group, SCC could improve the survival rate of injured cells, reduce the leakage of LDH into cell culture and reduce intracellular ROS (P < 0.01), increase the intracellular T-AOC and SOD activity (P < 0.01). CONCLUSION: SCC has significantly protective effect on the injured PC12 cells induced by H2O2. The results would provide preliminary data on supporting the development of sea cucumber as a functional food, which might give benefits to our brain.

Cerebroside D, a glycoceramide compound, improves experimental colitis in mice with multiple targets against activated T lymphocytes.

In the present paper, we aimed to examine the novel effects of cerebroside D, a glycoceramide compound, on murine experimental colitis. Cerebroside D significantly reduced the weight loss, mortality rate and alleviated the macroscopic and microscopic appearances of colitis induced by dexran sulfate sodium. This compound also decreased the levels of TNF-α, IFN-γ and IL-1ß in intestinal tissue of mice with experimental colitis in a concentration-dependent manner, accompanied with markedly increased serum level of IL-10. Cerebroside D inhibited proliferation and induced apoptosis of T cells activated by concanavalin A or anti-CD3 plus anti-CD28 antibodies. The compound did not show an effect on naive lymphocytes but prevented cells from entering S phase and G2/M phase during T cells activation. Moreover, the treatment of cerebroside D led to apoptosis of activated T cells with the cleavage of caspase 3, 9, 12 and PARP. These results showed multiple effects of cerebroside D against activated T cells for a novel approach to treatment of colonic inflammation.