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Biomedical subjects

Wei-Min Zhao

Publications and source records attributed to Wei-Min Zhao.

9 recordsLinked to original sources
PubMed2006

Periplocoside E inhibits experimental allergic encephalomyelitis by suppressing interleukin 12-dependent CCR5 expression and interferon-gamma-dependent CXCR3 expression in T lymphocytes.

Periplocoside E (PSE) was found to inhibit primary T-cell activation in our previous study. Now we examined the effect and mechanisms of PSE on the central nervous system (CNS) demyelination in experimental allergic encephalomyelitis (EAE). C57BL/6 mice immunized with myelin oligodendrocyte glyco-protein (MOG) were treated with PSE following immunization and continued throughout the study. The effect on the progression of EAE and other relevant parameters were assessed. PSE reduced the incidence and severity of EAE. Spinal cord histopathology analysis showed that the therapeutic effect of PSE was associated with reduced mononuclear cell infiltration and CNS inflammation. As reverse transcription-polymerase chain reaction analysis showed, PSE decreased the CD4(+), CD8(+), and CD11b(+) cell infiltration. T cells from lymph nodes of MOG-immunized mice expressed enhanced levels of CCR5 and CXCR3 mRNA compared with T cells from normal mice. However, CCR5 and CXCR3 expressions were suppressed in T cells from PSE-treated mice. In vitro study also showed PSE inhibited interferon (IFN)-gamma-dependent CXCR3 expression in T cells through suppressing T-cell receptor (TCR) ligation-induced IFN-gamma production, whereas it inhibited interleukin (IL)-12-dependent CCR5 expression through suppressing IL-12 reactivity in TCR-triggered T cells. As a result, the initial influx of T cells into CNS was inhibited in PSE-treated mice. The consequent activation of macrophages/microglia cells was inhibited in spinal cord from PSE-treated mice as determination of chemokine expressions (CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10). Consistently, the secondary influx of CD4(+), CD8(+), and CD11b(+) cells was decreased in spinal cords from PSE-treated mice. These findings suggest the potential therapeutic effect of PSE on multiple sclerosis.

Amino Acid Sequence↗
PubMed2005

Periplocoside E, an effective compound from Periploca sepium Bge, inhibited T cell activation in vitro and in vivo.

Periploca sepium Bge, a traditional Chinese herb medicine, is used for treating rheumatoid arthritis in China. Followed the bioactivity-guided isolation, the most potent immunosuppressive compound, periplocoside E (PSE), a pregnane glycoside, had been identified from P. sepium Bge. We investigated the immunosuppressive effects of PSE in vitro and in vivo. The results showed that PSE in a dose-dependent manner significantly inhibited the proliferation of splenocytes induced by concanavalin A and mixed lymphocyte culture reaction at no cytotoxic concentrations (<5 microM). Administration of PSE suppressed a delayed-type hypersensitivity reaction, and ovalbumin (OVA) induced antigen-specific immune responses in mice. In vivo treatment with PSE dose dependently suppressed OVA-induced proliferation and cytokine [interleukin (IL)-2 and interferon (IFN)-gamma] production from splenocytes in vitro. Purified T cells from OVA-immunized mice with PSE treatment showed its low ability for activation by OVA plus normal antigen presenting cell stimulation again in vitro. Further studies showed PSE dose dependently inhibited anti-CD3-induced primary T cell proliferation, activation for IL-2Ralpha (CD25) expression, and cytokine (IFN-gamma and IL-2) production also at the transcriptional level. PSE was highly specific and significantly inhibited the activation of extracellular signal-regulated kinase and Jun N-terminal kinase, whereas activation of p38 was not affected in T cells stimulated with anti-CD3. These results demonstrated that PSE is an immunosuppressive compound in P. sepium Bge, which directly inhibits T cell activation in vitro and in vivo. This study provided evidence to understand the therapeutic effects of P. sepium Bge and indicated that this herb is appropriate for treatment of T cell-mediated disorders, such as autoimmune diseases.

Animals↗
PubMed2005

The p53 pathway is synergized by p38 MAPK signaling to mediate 11,11'-dideoxyverticillin-induced G2/M arrest.

The phytochemical 11,11'-dideoxyverticillin, derived from the fungus Shiraia bambusicola, has been shown to possess potent anticancer activity in vitro and in vivo. Here, we investigated the effect of 11,11'-dideoxyverticillin on cell cycle progression, and explored the potential mechanisms for this effect. A concentration- and time-dependent cell cycle blockade at G2/M phase was observed in human colon cancer cells (HCT-116) following 11,11'-dideoxyverticillin treatment and was associated with marked increases in levels of p53, phospho-p53(ser20) and phospho-Chk2(Thr 68). When wild type p53 expression was specifically inhibited by RNA interference, HCT-116 cells treated with 11,11'-dideoxyverticillin failed to arrest in G2/M and did not show increased phospho-Chk2(Thr 68). On the other hand, 11,11'-dideoxyverticillin treatment also elicited p38 MAP kinase activity and expression of phospho-p38 MAPK. Treatment with a specific p38 MAPK inhibitor (SB203580) successfully inhibited p38 MAPK and delayed the onset of G2/M arrest induced by 0.5 microM 11,11'-dideoxyverticillin after approximately 6 h, but did not abolish the induction of G2/M arrest. Additionally, SB203580 did not alter the levels of p53, phospho-p53 (ser20), or phospho-Chk2 (Thr68) proteins in 11,11'-dideoxyverticillin-treated cells. Together, these findings indicate that p53-mediated phosphorylation of Chk2 maybe plays a vital role in 11,11'-dideoxyverticillin-induced G2/M arrest, and that p38 MAPK might accelerate this progression. Our work suggests a new possibility of interactions among p53, Chk2 and p38 MAPK signaling in G2/M arrest.

Antineoplastic Agents, Phytogenic↗
PubMed2005

Antiangiogenic activity of 11,11'-dideoxyverticillin, a natural product isolated from the fungus Shiraia bambusicola.

The fungus Shiraia bambusicola yields the phytochemical 11,11'-dideoxyverticillin, which has been shown to possess potent anticancer activity both in vitro and in vivo. In this study, we reveal that 11,11'-dideoxyverticillin has anti-angiogenic activities and explore the potential mechanisms for this effect. Treatment with 11,11'-dideoxyverticillin inhibited the proliferation of human umbilical vein endothelial cells (HUVECs) with IC(50) values of 0.17+/-0.05muM for VEGF-stimulated cells and 0.39+/-0.08muM for serum-stimulated cells. 11,11'-Dideoxyverticillin also antagonized the antiapoptotic effects of VEGF on serum-deprived HUVECs, inhibited VEGF-induced HUVEC migration in vitro, and blocked serum-induced HUVEC tube formation. Moreover, 11,11'-dideoxyverticillin completely blocked VEGF-induced microvessel sprouting from Matrigel-embedded rat aortic rings and vessel growth in Matrigel plugs in mice. In addition, 11,11'-dideoxyverticillin decreased VEGF secretion by MDA-MB-468 breast cancer cells, and significantly suppressed VEGF-induced tyrosine phosphorylation of Flt-1 and KDR/Flk-1. This inhibition of receptor phosphorylation was correlated with a marked decrease in VEGF-triggered pERK activation and a dramatic increase in pP38 MAPK, but no apparent change in pAkt. Together, these findings strongly suggest that 11,11'-dideoxyverticillin is a structurally novel angiogenesis inhibitor.

Angiogenesis Inhibitors↗
PubMed2005

11,11'-dideoxy-verticillin: a natural compound possessing growth factor receptor tyrosine kinase-inhibitory effect with anti-tumor activity.

11,11'-dideoxy-verticillin, a compound of the novel epidithiodioxopiprazine structural class, is isolated from the traditional Chinese medicinal herb Shiraia bambusicola. The present study demonstrated for the first time that 11,11'-dideoxy-verticillin has potent tyrosine kinase-inhibitory and anti-tumor activities. In the cell-free ELISA tyrosine kinase assay, 11,11'-dideoxy-verticillin significantly inhibited the activities of epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1 (VEGFR-1/Flt-1) and human epidermal growth factor receptor-2 (HER2/ErbB-2), with relative specificity on EGFR and VEGFR-1 with IC50s of 0.136+/-0.109 and 1.645+/-0.885 nM, respectively. Exposure of 11,11'-dideoxy-verticillin for 1 h to EGFR-overexpressed MDA-MB-468 human breast carcinoma cells and HER2-overexpressed SK-OV-3 human ovarian adenocarcinoma cells resulted in obvious inhibition of EGF-induced phosphorylation of EGFR and HER2. In addition, 11,11'-dideoxy-verticillin also inhibited the EGF-induced phosphorylation of Erk1/2, but had no effect on the phosphorylation of AKT in both tumor cell lines. Moreover, 11,11'-dideoxy-verticillin has potent anti-tumor activity. In vitro cytotoxicity assay showed that 11,11'-dideoxy-verticillin potently inhibited the proliferation of four human breast tumor cell lines with an average IC50 value of 0.2 microM. In vivo, 11,11'-dideoxy-verticillin exhibited remarkable efficacy against mice sarcoma 180 and hepatoma 22 after daily i.p. administration of 0.5 or 0.75 mg/kg with inhibition rates ranging from 45.0 to 72.4%. Treated with 11,11'-dideoxy-verticillin at 0.5-2.0 microM for 36 h, MB-MB-468 cells exhibited significant apoptotic morphological changes. At low concentrations (0.0625-0.5 microM) for 24 h, 11,11'-dideoxy-verticillin induced a dose-dependent accumulation of MDA-MB-468 cells in the G2/M phase of the cell cycle. These results indicate that 11,11'-dideoxy-verticillin is a naturally derived growth factor receptor tyrosine kinase inhibitor with potent anti-tumor activity.

Animals↗
PubMed2004

Evaluation of active recombinant catalytic domain of human ErbB-2 tyrosine kinase, and suppression of activity by a naturally derived inhibitor, ZH-4B.

Human cancers frequently express high levels of ErbB-2 tyrosine kinase, which is associated with aggressive tumor behavior and poor prognosis. ErbB-2 is thus a promising target for cancer therapy. Here we express the catalytic domain of ErbB-2 as a soluble active kinase, and investigate the correlations between its activity and kinase concentration, ATP concentration, substrate concentration and divalent cation type. A simple and effective screening model is established to identify and evaluate potential inhibitors of ErbB-2 kinase. ZH-4B, a naturally derived small molecule compound that potently inhibits ErbB-2 kinase activity with an IC50 value of 2.45+/-0.56 microM, is identified. In SK-OV-3 human ovarian cancer cells and SK-BR-3 human breast carcinoma cells, ZH-4B blocks epidermal growth factor (EGF)-induced phosphorylation of ErbB-2 in a dose-dependent manner. Our data collectively indicate that ZH-4B is a potential novel anti-cancer agent that deserves further investigation.

Animals↗
PubMed2004

Lignans from Dendrobium chrysanthum.

A new neolignan glucoside denchyside B along with three known lignans have been isolated from the herbs of Dendrobium chrysanthum Wall. (Orchidaceae). The structures were elucidated on the basis of spectroscopic methods.

Dendrobium↗
PubMed2002

Low dose of resveratrol enhanced immune response of mice.

AIM: To study the immune modulating effect of low dose of resveratrol. METHODS: Concanavalin A (ConA) and Staphylococcus aureus Cowan (Sac) were used to induce the activation of T lymphocyte and antigen presenting cell and cytokine production. [3H]-Thymidine incorporation was used to evaluate the proliferation of lymphocyte. Cytokine production was detected by ELISA method. Dinitrofluorobenzene (DNFB) was used to induce mice delayed type hypersensitivity (DTH, delayed hypersensitivity) response and ear swelling was used as an evaluating indicator. Changes of lymphocyte subtypes were detected by flow cytometry. RESULTS: Resveratrol (0.75-6 micromol/L) concentration-dependently promoted lymphocyte proliferation and IL-2 production induced by ConA. Sac induced IL-12 and IFN-gamma (interferon type II) production were also concentration-dependently enhanced by resveratrol, while IL-10 production was inhibited. Resveratrol (4 mg/kg, ig) promoted DTH response of mouse, which was suppressed by ethanol (16 %, w/v) consumption. Resveratrol treatment had no significant influence on lymphocyte subtypes in mice, however it could reverse the suppressive effect of ethanol both on macrophage percentage and on macrophage MHC-II molecule expression. CONCLUSION: Low dose resveratrol enhanced cell-mediate immune response. Promoting Th1 cytokine production and influencing on macrophage function might be its mechanisms.

Adjuvants, Immunologic↗