Asperustins A-J: Austocystins with Immunosuppressive and Cytotoxic Activities from Aspergillus ustus NRRL 5856.

Ten new (1-10) and nine known (11-19) austocystins, along with four known anthraquinones (20-23), were isolated from the culture of Aspergillus ustus NRRL 5856 by bioactivity-guided fractionation. The structures of the new compounds were elucidated by spectroscopic data analysis, X-ray crystallographic study, the modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD spectral analysis, and comparison of the experimental ECD spectra with those of the similar analogues. Compounds 1-8 represent the first examples of austocystins with a C-4' oxygenated substitution. The absolute configuration of 1″-hydroxy austocystin D (11) was determined by single-crystal X-ray diffraction and consideration of its biosynthetic origin. Compounds 5, 9, and 11 exhibited significant inhibitory effects against the proliferation of ConA-induced T cells with IC50 values of 1.1, 1.0, and 0.93 µM, respectively. Furthermore, these compounds suppressed the expression of IL-6 in a dose-dependent manner. Compounds 10-12 and 14 showed pronounced cytotoxicities against MCF-7 with IC50 values of 3.9, 1.3, 0.46, and 2.3 µM, respectively.

Polyphenols extracted from Enteromorpha clathrata alleviates inflammation in lipopolysaccharide-induced RAW 264.7 cells by inhibiting the MAPKs/NF-κB signaling pathways.

ETHNOPHARMACOLOGY RELEVANCE: Enteromorpha has long been recorded in traditional Chinese medicine, with cholesterol-lowering, anti-cancer, anti-inflammatory and antibacterial effects. Recently, we extracted the polyphenol-enriched fraction from Enteromorpha clathrata (E. clathrata) by ethyl acetate (ECPs), and isolated six individual polyphenols from ECPs via high-speed counter-current chromatography (HSCCC) with high-performance liquid chromatography (HPLC). AIM OF THE STUDY: In this study, we explored the anti-inflammatory activity and underlying mechanism of ECPs in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. MATERIALS AND METHODS: ECPs and the six polyphenols were used for nitric oxide (NO) assay to identify the components with potent inflammation inhibitory effect. Enzyme-linked immunosorbent assay (ELISA), quantitative real-time PCR (qPCR), flow cytometry, and Western blot analysis were applied to further investigate their anti-inflammatory effects and underlying mechanism in LPS-stimulated RAW264.7 cells. RESULTS: ECPs and the three individual polyphenols, including (-)-epicatechin, epigallocatechin-3-O-gallate and (-)-epicatechin-3-O-gallate, showed in vitro immunosuppressive activity by altering the cell biology at the gene, protein and functional levels in a dose- and species-dependent manner. Their anti-inflammatory effects were achieved by inhibiting LPS-induced production of nitric oxide and its upstream enzyme inducible nitric oxide synthase (iNOS), the pro-inflammatory cytokines including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), as well as the phagocytotic capacity, without cytotoxicity. The mechanism study further revealed that these anti-inflammatory properties were, at least partly, attributed to the suppressed activation of nuclear factor-κB (NF-κB) and p38 mitogen-activated protein kinase (MAPK) signaling pathways. CONCLUSIONS: These findings indicated for the first time the correlation between the anti-inflammatory activity of ECPs and NF-κB and MAPK signaling pathways, suggesting that polyphenol-enriched organic fraction of E. clathrata could be potential candidate as therapeutic agent for treating inflammatory diseases.

Resorcylic acid lactones from a Podospora sp. that induce apoptosis in activated T cells through MAPKs/AKT pathway.

Podomycins A-L (1-12), 12 undescribed hypothemycin-type resorcylic acid lactones (RALs), were characterized from Podospora sp. G214, an endophyte harbored in the roots of Sanguisorba officinalis L. Their structures were addressed by spectroscopic data, X-ray crystallography, the modified Mosher's method, together with Mo2(OAc)4- and Rh2(OCOCF3)4-induced electronic circular dichroism (ICD) experiments. Podomycins A-C (1-3) represent the first class of natural RALs with a 13-membered macrolactone ring, while 4-12 are rearranged methoxycarbonyl substituted RALs. Biologically, compounds 2, 6, 8, 10, and 12 displayed immunosuppressive activities against T cell proliferation with IC50 values of 14.5-21.9 µM, and B cell proliferation with IC50 values of 22.3-36.5 µM, respectively. Further mechanism of action research demonstrated that podomycin F (6) distinctly induced apoptosis in activated T cells via MAPKs/AKT pathway.

Structurally diverse biflavonoids from the fruits of Citrus medica L. var. sarcodactylis Swingle and their hypolipidemic and immunosuppressive activities.

The fruit of Citrus medica L. var. sarcodactylis Swingle is not only used as a traditional medicinal plant, but also served as a delicious food. Six new (3'→7″)-biflavonoids (1-6), and twelve known biflavonoid derivatives (7-18) were isolated and characterized from the fruits of C. medica L. var. sarcodactylis Swingle for the first time. Their structures were determined by extensive and comprehensive analyzing NMR, HR-ESI-MS, UV, and IR spectral data coupled with the data described in the literature. Compounds (1-18) were evaluated for their hypolipidemic activities with Orlistat as the positive control, and assayed for their immunosuppressive activities with Dexamethasone as the positive control, respectively. Among them, compounds (1-3) exhibited moderate inhibition of pancreatic lipase activity by inhibiting 68.56 ± 1.40%, 56.18 ± 1.57%, 53.51 ± 1.59% of pancreatic lipase activities at the concentration of 100 µM, respectively. Compounds (4-6) and 8 showed potent immunosuppressive activities with the IC50 values from 16.83 ± 1.32 to 50.90 ± 1.79 µM. The plausible biogenetic pathway and preliminary structure activity relationship of the selected compounds were scientifically summarized and discussed in this study.

Polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from Hypericum perforatum and absolute configurations assignment of previously reported analogues.

Hyperformitins A-I (1-9), nine undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) with double-bond migration, along with four new isomers hyperformitins J-M (10-13), were isolated from Hypericum perforatum. Their structures and absolute configurations were determined by spectroscopic analyses including HRESIMS, IR, UV, NMR, and ECD, as well as optical rotation (OR) calculations. The absolute configurations of previously reported analogues, garsubellins D and C as well as garcinielliptones L and M, were assigned for the first time by NMR spectra and specific rotations analyses assisting with OR calculations. Selected compounds were tested for their immunosuppressive activities against lipopolysaccharide (LPS)-induced B lymphocyte proliferation. Compounds 1, 3, 4, 5, 7, and 11 showed inhibition activities against the proliferation of B lymphocyte with IC50 values ranging from 4.1 to 9.7 µM. Furthermore, the neuroprotective activities of the isolates against corticosterone (CORT)-induced injury in PC12 cells were also tested, and compounds 1, 12, and 13 exhibited neuroprotective effects with cell viabilities of 68.0%, 71.3%, and 68.4%, respectively under the concentration of 10 µM.

Spiro ent-Clerodane Dimers: Discovery and Green Approaches for a Scalable Biomimetic Synthesis.

Scospirosins A (1) and B (2), two unprecedented spiro ent-clerodane dimers with 6/6/10/6 and 6/6/6/6/6 ring systems, respectively, were isolated from Isodon scoparius. Their structures were unambiguously established by spectroscopic, X-ray crystallographic, and chemical approaches. A bioinspired protecting-group-free strategy for their synthesis was achieved on a gram scale and featured the application of green methods, including neat reaction, sensitized photooxygenation, and electrochemical oxidation. 2 exhibited selective immunosuppressive activity against the proliferation of T lymphocytes (IC50 = 1.42 µM).

Actinobacteria in natural products research: Progress and prospects.

Actinobacteria are well-recognised biosynthetic factories that produce an extensive spectrum of secondary metabolites. Recent genomic insights seem to impact the exploitation of these metabolically versatile bacteria in several aspects. Notably, from the isolation of novel taxa to the discovery of new compounds, different approaches evolve at a steady pace. Here, we systematically discuss the enduring importance of Actinobacteria in the field of drug discovery, the current focus of isolation efforts targeting bioactive Actinobacteria from diverse sources, recent discoveries of novel compounds with different bioactivities, and the relative employment of different strategies in the search for novel compounds. Ultimately, we highlight notable progress that will have profound impacts on future quests for secondary metabolites of Actinobacteria.

Prunella vulgaris L. attenuates experimental autoimmune thyroiditis by inducing indoleamine 2,3-dioxygenase 1 expression and regulatory T cell expansion.

BACKGROUND: Prunella vulgaris L. (P. vulgaris) has traditionally been used to treat swelling and inflammation of the thyroid gland. This study aimed to evaluate the effects of P. vulgaris on experimental autoimmune thyroiditis (EAT) and explore the roles of indoleamine 2,3-dioxygenase 1 (IDO1) and regulatory T cells (Tregs) in these P. vulgaris-mediated effects. METHODS: The main bioactive compounds in P. vulgaris were analysed by high-performance liquid chromatography. An EAT model was established by immunization of Lewis rats with thyroglobulin via subcutaneous injection. Thyroid volume was assessed by ultrasound, and lymphatic infiltration in the thyroid was evaluated by haematoxylin and eosin staining. The serum levels of thyroglobulin antibody (TgAb) and cytokines were measured by indirect enzyme-linked immunosorbent assay. The percentage of CD4+CD25+Foxp3+ Tregs was detected by flow cytometry. The mRNA and protein levels of IDO1 were measured by qRT-PCR and Western blotting, respectively. The levels of tryptophan (Trp) and kynurenine (Kyn) in serum and faecal samples were assessed with a fluorometric kit and spectrophotometry. RESULTS: The main bioactive compound in P. vulgaris was rosmarinic acid. The TgAb level and thyroid volume in EAT rats were significantly decreased after administration of P. vulgaris (P < 0.01). The inflammation score in EAT rats that were administered P. vulgaris was significantly lower than that in the EAT controls (P < 0.01). In addition, P. vulgaris promoted the expansion of splenic Tregs and increased the production of IL-10 and TGF-ß (P < 0.01) in EAT rats. Moreover, P. vulgaris induced IDO1 mRNA and protein expression in the spleen and intestine in P. vulgaris-treated EAT rats (P < 0.01). Finally, Trp levels were reduced and Kyn levels and the Kyn/Trp ratio were increased in the serum of P. vulgaris-treated EAT rats. CONCLUSION: We were the first to demonstrate the role of IDO1-induced Treg expansion in P. vulgaris-mediated attenuation of EAT. Our study provides insight into the immunopathogenesis of autoimmune thyroiditis and shows the potential therapeutic value of P. vulgaris.

Schizophyllum commune induced oxidative stress and immunosuppressive activity in Spodoptera litura.

BACKGROUND: In the last few decades, considerable attention has been paid to fungal endophytes as biocontrol agents, however little is known about their mode of action. This study aimed to investigate the toxic effects of an endophytic fungus Schizophyllum commune by analyzing activities of antioxidant and detoxifying enzymes as well as morphology of haemocytes using Spodoptera litura as a model. RESULTS: Ethyl acetate extract of S. commune was fed to the larvae of S. litura using the artificial diet having 276.54 µg/ml (LC50 of fungus) concentration for different time durations. Exposed groups revealed significant (p ≤ 0.05) increase in the activities of various enzymes viz. Catalase, Ascorbate peroxidase, Superoxide dismutase, Glutathione-S-Transferase. Furthermore, haemocytes showed various deformities like breakage in the cell membrane, cytoplasmic leakage and appearance of strumae in the treated larvae. A drastic reduction in the percentage of normal haemocytes was recorded in the treated groups with respect to control. CONCLUSION: The study provides important information regarding the oxidative stress causing and immunosuppressant potential of S. commune against S. litura and its considerable potential for incorporation in pest management programs.

The immunosuppressive functions of two novel tick serpins, HlSerpin-a and HlSerpin-b, from Haemaphysalis longicornis.

Serpins are evolutionarily conserved serine protease inhibitors that are widely distributed in animals, plants and microbes. In this study, we reported the cloning and functional characterizations of two novel serpin genes, HlSerpin-a and HlSerpin-b, from the hard tick Haemaphysalis longicornis of China. Recombinant HlSerpin-a and HlSerpin-b displayed protease inhibitory activities against multiple mammalian proteases. Similar to other tick serpins, HlSerpin-a and HlSerpin-b suppressed the expression of inflammatory cytokines such as TNF-α, interleukin (IL)-6 and IL-1ß from lipopolysaccharide-stimulated mouse bone-marrow-derived macrophages (BMDMs) or mouse bone-marrow-derived dendritic cells (BMDCs). The minimum active region (reaction centre loop) of HlSerpin-a, named SA-RCL, showed similar biological activities as HlSerpin-a in the protease inhibition and immune suppression assays. The immunosuppressive activities of full-length HlSerpin-a and SA-RCL are impaired in Cathepsin G or Cathepsin B knockout mouse macrophages, suggesting that the immunomodulation functions of SA and SA-RCL are dependent on their protease inhibitory activity. Finally, we showed that both full-length HlSerpins and SA-RCL can relieve the joint swelling and inflammatory response in collagen-induced mouse arthritis models. These results suggested that HlSerpin-a and HlSerpin-b are two functional arthropod serpins, and the minimal reactive peptide SA-RCL is a potential candidate for drug development against inflammatory diseases.

Selenium-containing polysaccharides from Lentinula edodes-Biological activity.

We hypothesized that selenium(Se)-enriched polysaccharides would possess superior biological activity when compared to those non-enriched. To verify this hypothesis, we obtained by biotechnological methods a Se-enriched analog of Japanese anticancer drug lentinan and, as a reference, the non-Se-enriched fraction. We tested the effects of the obtained fractions on the proliferation of human peripheral blood mononuclear cells. The results suggested a selective immunosuppressive activity, non-typical for mushroom derived polysaccharides. Both fractions caused significant inhibition of human T lymphocyte proliferation induced by mitogens, without significant effects on B lymphocytes. The inhibitory effect was not due to the toxicity of the examined polysaccharides. In normal (HUVEC) or malignant (HeLa) cells tested fractions significantly enhanced cell viability and protected the cells from oxidative stress conditions. However, we observed no effect of the polysaccharide fractions on the production of reactive oxygen species by granulocytes in vitro. The selenium content increased the biological activity of the tested polysaccharide fractions.

Przewalcyrones A-F, epoxychromene-containing polycyclic polyprenylated acylphloroglucinols with immunosuppressive activity from Hypericum przewalskii Maxim.

Chemical investigation of the extracts of the aerial parts of Hypericum przewalskii Maxim. resulted in the isolation and identification of six new epoxychromene-containing polycyclic polyprenylated acylphloroglucinols (PPAPs), named przewalcyrones A-F (1-6), and one known analogue (7). All of the structures were determined based on extensive spectroscopic analyses, X-ray crystallographic analysis, modified Mosher's method, [Rh2(OCOCF3)4]-induced ECD, and electronic circular dichroism (ECD) comparison. Structurally, przewalcyrones A-F represent the first examples of PPAPs containing an unexpected 8,8-dimethyl-3,9-epoxychromene moiety. All these compounds were evaluated for the immunosuppressive activity in anti-CD3/anti-CD28 monoclonal antibody (mAb)-stimulated human T cells. Among them, przewalcyrones C and D exhibited potential in vitro immunosuppressive activity, with IC50 values of (5.01 ± 0.52) µM and (5.26 ± 0.56) µM, respectively, highlighting those compounds as a promising starting point for the development of new immunosuppressive agents.

Biofunctional Effects of Thiohemiaminal-Type Dimeric Sesquiterpene Alkaloids from Nuphar Plants.

Dimeric sesquiterpene thioalkaloids from the rhizomes of Nuphar pumilum exhibited immunosuppressive effects using a sheep erythrocyte plaque forming cell (PFC) assay, as well as an anti-metastasis effect, and rapid apoptosis-inducing effects in tumor cell lines. In particular, dimeric sesquiterpene thioalkaloids with a hydroxy group (6-hydroxythiobinupharidine, 6,6'-dihydroxythiobinupharidine, 6-hydroxythionuphlutine B) showed substantial effects, whereas dimeric sesquiterpene thioalkaloids lacking the hydroxy group (thiobinupharidine, thionuphlutine B, 6'-hydroxythionuphlutine B, neothiobinupharidine, thionuphlutine B ß-sulfoxide, neothiobinupharidine ß-sulfoxide) and monomeric sesquiterpene alkaloids (nupharidine, 7-epideoxynupharidine, nupharolutine) showed weak activity. In this review, we summarize our studies of the biofunctional effects of these alkaloids.

Immunosuppressive effects of protein derivatives from Mucuna pruriens on a streptozotocin-induced type 1 diabetes murine model.

Type 1 diabetes is an autoimmune disease induced by abnormal insulin secretions from ß-cells in pancreas. The present study aimed to investigate the immunosuppressive effects from protein derivatives of Mucuna pruriens on a murine model of Type 1 diabetes. Hydrolyzate and five peptide fractions with different molecular weight were administered orally by 14 days, followed T1D murine model was built by intraperitoneal injection of streptozotocin over 5 days. The mice weight, blood glucose levels, anti-insulin, and anti-pancreatic islet ß-cells antibodies, pro-inflammatory cytokines as tumor necrosis factor alpha and interleukin-6 were determined in four times (0, 15, 30, and 45 day). Mice were sacrificed and pancreatic tissues samples were obtained and staining with hematoxylin and eosin to determine the degree of damage. The study demonstrated immunosuppressive activity in four of the six treatment groups: (a) T1D PPH, (b) T1D F 5-10 kDa, (c) T1D F 3-5 kDa, and (d) T1D F 1-3 kDa. PRACTICAL APPLICATIONS: Due to the high content of native protein in seeds of Mucuna pruriens, studies have reported potential in the elaboration of hydrolysates and peptides with biological activity. These protein derivatives could help in the treatment of immunological disorders that are observed in several chronic non-communicable disease and inflammatory diseases, such as T1D. Activated macrophages and lymphoplasmacytic infiltrate plays a crucial role in the initiation and maintenance of T1D; therefore, several studies has focused to reduce the effector functions of this cells for diminishing the clinical manifestations in inmmunocompromised patients. Thus, this study indicates the potential application of hydrolyzate and peptide fractions of M. pruriens in functional foods and dietary supplements could be developed for the treatment of inflammatory and chronic non-communicable diseases.

Pigments from Soil Bacteria and Their Therapeutic Properties: A Mini Review.

Advancement in research on dyes obtained from natural sources e.g., plants, animals, insects and micro-organisms is widening the application of natural dyes in various fields. The natural dyes substituted their synthetic analogs at the beginning of twentieth century due to their improved quality, value, ease of production, ease of dyeing and some other factors. This era of dominance ended soon when toxic effects of synthetic dyes were reported. In the last few decades, pigments from micro-organisms especially soil derived bacteria is replacing dyes from other natural sources because of the increasing demand for safe, non-toxic, and biodegradable natural product. Apart from application in agriculture practices, cosmetics, textile, food and paper industries, bacterial pigments have additional biological activities e.g., anti-tumor, anti-fungal, anti-bacterial, immunosuppressive anti-viral, and many more which make them a potential candidate for pharmaceutical industry. Optimization of culture conditions and fermentation medium is the key strategies for large scale production of these natural dyes. An effort has been done to give an overview of pigments obtained from bacteria of soil origin, their dominance over dyes from other sources (natural and synthetic) and applications in the medical world in the underlying study.

In vitro combinatorial anti-proliferative and immunosuppressive effects of Brucea javanica extract with CX-4945 and imatinib in human T-cell acute lymphoblastic leukemia cells.

Since 1970, the isolated and identified components of Brucea javanica (L.) Merr. have been known to contain anticancer effects, particularly antileukemic effect. In this study, the inhibitory effect of Brucea javanica (BJ) on cell growth and inflammation was confirmed in human T-cell acute lymphocytic leukemia (T-ALL) cells, and its efficacy as an antileukemic agent was verified. Our results showed that BJ extract induced caspase-dependent apoptosis of T-ALL Jurkat cells through inhibition of the CK2-mediated signaling pathway, while exerting no significant cytotoxicity in normal peripheral blood mononuclear cells. Moreover, BJ extract suppressed the NF-κB signaling pathway, thus, inhibiting the interleukin (IL)-2 expression induced by phorbol 12-myristate 13-acetate (PMA) and phytohemagglutinin (PHA). Notably, combined treatment with BJ extract plus CX-4945 or imatinib exerted enhanced inhibitory effects on T-ALL cell growth and IL-2 production. Overall, these results suggest that BJ extract can be a potent therapeutic herbal agent for T-ALL treatment and prevention of IL-2 mediated inflammatory immune responses.

Isolation, Structure Elucidition, and Immunosuppressive Activity of Diterpenoids from Ligularia fischeri.

Six new (1-3 and 6-8) and seven known diterpenoids were isolated from the whole plant of Ligularia fischeri. Compound 1 is a new 15,16-dinorerythroxylane-type diterpenoid possessing a C18 skeleton, and 2 is the first example of a 6/6/6/6/5/5-fused hexacyclic ent-kaurane diterpenoid with 19,20-olide and 11,16-epoxy moieties. The structures of the new compounds were elucidated by spectroscopic analysis and chemical methods. The absolute configurations of 1 and 7 were determined by single-crystal X-ray diffraction. Compounds 1-13 were evaluated for their immunosuppressive activity, and 4, 7, and 13 showed moderate inhibitory activities against human B lymphoblast HMy2.CIR cells with IC50 values of 56.3 ± 2.2, 13.3 ± 0.8, and 31.4 ± 0.9 µM, respectively.

PG2, a botanically derived drug extracted from Astragalus membranaceus, promotes proliferation and immunosuppression of umbilical cord-derived mesenchymal stem cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus membranaceus is used to manage the deficiency of vital energy in traditional Chinese medicine and confirmed to have many biological functions. Mesenchymal stem cells (MSCs) possess immunosuppressive effects, and are widely used for regenerative medicine and immune disorders. AIMS OF STUDY: This study investigated the effects of Astragalus polysaccharides (APS) on umbilical cord-derived MSCs (UCMSCs), including morphology, surface marker expression, proliferation, differentiation, and in-vitro and in-vivo immunosuppressive capacities. MATERIALS AND METHODS: MSCs isolated from umbilical cords were used. PG2 injection, a botanically derived drug containing a mixture of APS, was added into the culture medium to prepare PG2-treated UCMSCs. The morphology, surface marker expression, proliferation, and differentiation of UCMSCs were determined. The in-vitro immunosuppressive effects of UCMSCs were examined by peripheral blood mononuclear cell (PBMC) proliferation assay. The in-vivo effects were evaluated by circulatory inflammation-associated cytokine levels in mice with septic peritonitis induced by cecal ligation and puncture (CLP) operation. RESULTS: Compared with control UCMSCs, UCMSCs had higher population doublings when exposed to PG2-containing medium (P = 0.003). The reduction rates of PBMC proliferation after phytohemagglutinin stimulation increased significantly when UCMSCs were treated with PG2 (P = 0.004). The serum levels of inflammation-associated cytokines, including TNF-α, IL-6, MCP-1, IFN-γ, and IL-1ß, were significantly lower at 6h after CLP in the mice receiving PG2-treated UCMSCs. CONCLUSIONS: Our results demonstrated that PG2 can enhance UCMSC proliferation and their in-vitro and in-vivo immunosuppressive effects. Consequently, UCMSCs can be obtained in earlier passages to avoid senescence, and sufficient cells can be acquired faster for clinical use. With stronger immunosuppressive effects, UCMSCs may treat immune disorders more effectively. Further studies are warranted.

Immunosuppressive Effects of Bryoria sp. (Lichen-Forming Fungus) Extracts via Inhibition of CD8+ T-Cell Proliferation and IL-2 Production in CD4+ T Cells.

Lichen-forming fungi are known to have various biological activities, such as antioxidant, antimicrobial, antitumor, antiviral, anti-inflammation, and anti proliferative effects. However, the immunosuppressive effects of Bryoria sp. extract (BSE) have not previously been investigated. In this study, the inhibitory activity of BSE on the proliferation of CD8+ T cells and the mixed lymphocytes reaction (MLR) was evaluated in vitro. BSE was non-toxic in spleen cells and suppressed the growth of splenocytes induced by anti-CD3. The suppressed cell population in spleen cells consisted of CD8+ T cells and their proliferation was inhibited by the treatment with BSE. This extract significantly suppressed the IL-2 associated with T cell growth and IFN-γ as the CD8+ T cell marker. Furthermore, BSE reduced the expression of the IL-2 receptor alpha chain (IL-2Rα) on CD8+ T cells and CD86 on dendritic cells by acting as antigen-presenting cells. Finally, the MLR produced by the co-culture of C57BL/6 and MMC-treated BALB/c was suppressed by BSE. IL-2, IFN-γ, and CD69 on CD8+ T cells in MLR condition were inhibited by BSE. These results indicate that BSE inhibits the MLR via the suppression of IL-2Rα expression in CD8+ T cells. BSE has the potential to be developed as an anti-immunosuppression agent for organ transplants.

Novel immunosuppressive pregnane glycosides from the leaves of Epigynum auritum.

Phytochemical investigation on the leaves of Epigynum auritum led to the isolation of three novel C21 pregnane glycosides, epigynosides, E-G (1-3), together with two known pregnane glycosides, epigynosides A (4) and C (5). Their structures were elucidated based on extensive spectroscopic data (MS, IR, 1D and 2D NMR) analysis, as well as comparison with the reported data. The immunological activities of the new compounds was evaluated against concanavalin A (Con A)-stimulated proliferation of mice splenocyte in vitro. Compounds 1-3 displayed significant immunosuppressive activities, close to the efficacy of the positive control (dexamethasone) at the concentration of 50µM.