Category Archives: Types Of Extract

Immunotherapy, Medical Studies, PSP

Effects of polysaccharide peptides from COV-1 strain of Coriolus versicolor on glutathione and glutathione-related enzymes in the mouse.

Yeung JH, Or PM.

Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China. johnyeung@cuhk.edu.hk

Abstract

The effects of polysaccharide peptide (PSP), an immunomodulator isolated from Coriolus versicolor COV-1, on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of PSP (1-4 micromole/kg, i.p.) produced a transient, dose-dependent depletion (10-37%) of hepatic GSH, with no effect on serum glutamic-pyruvic transaminase (SGPT) activity. Blood GSH was depleted (6-25%) at 3 h, followed by a rebound increase above the control GSH level (20%) at 18 h. The GSSG/GSH ratio, a measure of oxidative stress, was increased 3 h after PSP treatment but returned to normal levels at 24 h. Sub-chronic treatment of PSP (1-4 micromole/kg/day, i.p.) for seven days did not produce any significant changes in hepatic GSH levels and the GSSG/GSH ratio when measured 24 h after the final dose of PSP. PSP had little effect on glutathione transferase (GST), glutathione reductase (GSSG reductase) and glutathione peroxidase (GPX) activities in the liver. However, a dose-dependent increase in blood GPX activity (30-48%) was observed at 3h, which coincided with the increase in the GSSG/GSH ratio. The increase in blood GPX activity may be a responsive measure to deal with the transient oxidative stress induced by PSP treatment. The results showed that PSP only caused a transient perturbation on hepatic glutathione without affecting the GSH-related enzymes such as GST, GSSG reductase and GPX. The observed changes in blood GSH simply reflected the intra-organ translocation of glutathione, as the glutathione-related enzymes were not significantly affected by PSP treatment.

PMID: 17240508 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/17240508

in vitro, Medical Studies, PSP

In vivo effect of I’m-Yunity on hepatic cytochrome P450 3A4.

Nicandro JP, Tsourounis C, Frassetto L, Guglielmo BJ.

Dept of Clinical Pharmacy, University of California, San Francisco, CA 94143, USA. ps01459@itsa.ucsf.edu

Abstract

The inhibition or induction of hepatic cytochrome P450 3A4 (CYP3A4) enzyme associated with herbal medicines such as I’m-Yunity (Coriolus versicolor) can result in clinically significant herb-drug interactions. The active ingredient of I’m-Yunity is believed to be polysaccharopeptide polymer (PSP). Drug interactions between I’m-Yunity and other medications or supplements are yet to be investigated. The objective of this single-treatment, one-period, three-phase, open-labeled study was to evaluate the ability of I’m-Yunity to inhibit or induce CYP3A4 in 12 healthy adult volunteers (8 women and 4 men) aged between 23 and 54 years through the use of a CYP3A4-specific assay, the erythromycin breath test (EBT). EBT measurements are reported as percentage of 14C-Erythromycin metabolized/hr. Participants were given a 14-day supply of I’m-Yunity and instructed to take 1200 mg, three times daily with meals. Comparisons of all subjects’ mean CYP3A4 activities were performed with the EBT before and after taking I’m- Yunity. Results revealed a mean EBT change (SD) from baseline of 0.08% (0.56%) 14C-Erythromycin metabolized/hr, which was not significant (p = 0.63). Therefore, 14 days of exposure to I’m-Yunity was not associated with clinically significant CYP3A4 inhibition or induction, suggesting that short-term administration of I’m-Yunity with medications primarily metabolized by CYP3A4 is safe and not expected to be associated with significant herb-drug interactions. However, it is still unknown whether interactions exist between I’m-Yunity and other medications metabolized by other CYP450 isozymes or enzyme/transporter systems.

PMID: 17594986 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/17594986

Autoimmune Disease, Breast Cancer, Cancer, Leukemia, Medical Studies, PSP

Polysaccharopeptide enhances the anticancer activity of doxorubicin and etoposide on human breast cancer cells ZR-75-30.

Wan JM, Sit WH, Louie JC.

Food and Nutritional Science Division, School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, PR China. jmfwan@hkusua.hku.hk

Abstract

In search of natural bioactive microbial compounds with adjuvant properties, we have previously showed that the polysaccharopeptide (PSP), isolated from Chinese medicinal mushroom Coriolus versicolor, was able to enhance the cytotoxicity of certain S-phase targeted-drugs on human leukemic HL-60 cells via some cell-cycle and apoptotic-dependent pathways. The present study aimed to investigate whether the synergism of mechanisms of PSP with certain chemotherapeutic drugs also applies to human breast cancer. PSP treatment enhanced the cytotoxicity of doxorubicin (Doxo), etoposide (VP-16) but not cytarabine (Ara-C). Bivariate bromodeoxyuridine (BrdUrd)/DNA flow cytometry analysis estimated a longer DNA synthesis time (Ts) for the PSP treated cancerous cells suggesting that PSP enhanced the apoptotic effect of Doxo and VP-16 via creating an S-phase trap in the human breast cancer cell line ZR-75-30. The participation of PSP in the apoptotic machinery of the chemotherapeutic agents was further supported by a reduced ratio of protein expression of Bcl-xL/Bax of the cancer cells. This study provides further insight into the synergistic mechanisms of PSP and supports the hypothesis that the anticancer potentials of PSP is not limited to leukemia but may also be used as an adjuvant therapy for breast cancers.

PMID: 18292947 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/18292947

Cancer, Immunotherapy, Medical Studies, PSK

The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis.

Jiménez-Medina E, Berruguilla E, Romero I, Algarra I, Collado A, Garrido F, Garcia-Lora A.

Servicio de Análisis Clínicos e Inmunologia, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Av, de las Fuerzas Armadas 2, 18014 Granada, Spain. evajimenez@fundacionhvn.org

Abstract

BACKGROUND: Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated.

METHODS: The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells.

RESULTS: PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.

CONCLUSION: These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

PMID: 18366723 [PubMed – indexed for MEDLINE]PMCID: PMC2291471Free PMC Article

http://www.ncbi.nlm.nih.gov/pubmed/18366723

Clinical Trials, Immunotherapy, Medical Studies, Melanoma, PSK, PSP

Evaluation of widely consumed botanicals as immunological adjuvants.

1 Comment

Ragupathi G, Yeung KS, Leung PC, Lee M, Lau CB, Vickers A, Hood C, Deng G, Cheung NK, Cassileth B, Livingston P.

Laboratory of Tumor Vaccinology, Melanoma and Sarcoma Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States. ragupatg@mskcc.org

Abstract

BACKGROUND: Many widely used botanical medicines are claimed to be immune enhancers. Clear evidence of augmentation of immune responses in vivo is lacking in most cases. To select botanicals for further study based on immune enhancing activity, we study them here mixed with antigen and injected subcutaneously (s.c.). Globo H and GD3 are cell surface carbohydrates expressed on glycolipids or glycoproteins on the cell surface of many cancers. When conjugated to keyhole limpet hemocyanin (KLH), mixed with an immunological adjuvant and administered s.c. the magnitude of the antibody responses against globo H, GD3 and KLH depend largely on the potency of the adjuvant. We describe here the results obtained using this s.c. immunization model with seven botanicals purported to have immune stimulant effects.

METHODS: Groups of 5-10 mice were immunized with globo H-KLH or GD3-KLH mixed with botanical, saline or positive control immunological adjuvant, s.c. three times at 1 week intervals. Antibody responses were measured 1 and 2 weeks after the 3rd immunization. The following seven botanicals and fractions were tested: (1) H-48 (Honso USA Co.), (2) Coriolus versicolor raw water extract, purified polysaccharide-K (PSK) or purified polysaccharide-peptide (PSP) (Institute of Chinese Medicine (ICM)), (3) Maitake extract (Yukiguni Maitake Co. Ltd. and Tradeworks Group), (4) Echinacea lipophilic, neutral and acidic extracts (Gaia Herbs), (5) Astragalus water, 50% or 95% ethanol extracts (ICM), (6) Turmeric supercritical (SC) or hydro-ethanolic (HE) extracts (New Chapter) or 60% ethanol extract (ICM) and (7) yeast beta-glucan (Biotec Pharmacon). Purified saponin extract QS-21 (Antigenics) and semisynthetic saponin GPI-0100 (Advanced BioTherapies) were used as positive control adjuvants. Sera were analyzed by ELISA against synthetic globo H ceramide or GD3 and KLH.

RESULTS: Consistent significant adjuvant activity was observed after s.c. vaccination with the Coriolus extracts (especially PSK), a 95% ethanol extract of Astragalus and yeast beta-glucan, and (to a lesser extent) Maitake. Antibodies against KLH in all cases and against globo H in most cases were induced by these botanicals. Little or no adjuvant activity was demonstrated with H-48 or Echinacea extracts or the Astragalus water extract. Experiments with GD3-KLH as immunogen confirmed the adjuvant activity of the Coriolus, yeast beta-glucan and Astragalus extracts. While extraction with ethanol concentrated the active ingredients in Astragalus, it had no impact on Coriolus where the 90% ethanol precipitate and solute were equally active.

CONCLUSIONS: Some, but not all, botanicals purported to be immune stimulants had adjuvant activity in our model. PSK and Astragalus were surprisingly active and are being further fractionated to identify the most active adjuvant components.

PMID: 18640165 [PubMed – indexed for MEDLINE]PMCID: PMC2565601

http://www.ncbi.nlm.nih.gov/pubmed/18640165

PSK, PSP, Types Of Extract

Production and structural analysis of the polysaccharide secreted by Trametes (Coriolus) versicolor ATCC 200801.

Rau U, Kuenz A, Wray V, Nimtz M, Wrenger J, Cicek H.

Institute of Biochemistry and Biotechnology, Technical University Braunschweig, Spielmannstr. 7, 38106 Braunschweig, Germany. U.Rau@tu-bs.de

Abstract

Trametes versicolor ATCC 200801 secretes 4.1 g L(-1) of exopolysaccharide (EPS) when synthetic minimal medium and low-shear bioreactor cultivation technique are used. Structural and compositional analyses by thin layer chromatography, gas chromatography-mass spectrometry, electrospray ionization tandem mass spectrometry, and nuclear magnetic resonance spectroscopy yielded predominantly glucose and small amounts of galactose, mannose, arabinose, and xylose. The main EPS is composed of beta-1,3/beta-1,6-linked D-glucose molecules which is identical with Schizophyllan but does not possess a triple helical arrangement as secondary structure. Two molar mass fractions were detected by size exclusion chromatography yielding weight-average molecular weights of 4,100 and 2.6 kDa. Protein content varies between 2-3.6% (w/w). The exopolysaccharide is different in the nature of the glycosidic linkage, composition of monosaccharides, protein content, and weight-average molecular weight compared to the well-known polysaccharopeptide (PSP) and polysaccharopeptide Krestin (PSK).

PMID: 18800181 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/18800181

Cancer, Immunotherapy, Medical Studies, PSK

Protein-bound polysaccharide-K (PSK) directly enhanced IgM production in the human B cell line BALL-1

Maruyama S, Akasaka T, Yamada K, Tachibana H.

Laboratory of Food Chemistry, Division of Applied Biological Chemistry, Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, Higashi-ku, Fukuoka, Japan. marushins2003@ybb.ne.jp

Abstract

Protein-bound polysaccharide-K (PSK) prepared from the basidiomycete Coriolus versicolor has been used as a biological response modifier for the treatment of cancer patients. Many studies describing the immunomodulatory effects and direct anti-cancer effects of PSK have been reported. Most of studies describing the immunomodulatory effects focused on cellular immunity, although there were several studies which focused on humoral immunity where PSK was shown to be able to induce antibody production in vivo. However, even in these humoral immunity studies, it is thought that the enhancement of antibody production was due to the activation of cellular immunity. In this study, we investigated the direct effect of PSK on B cells and discovered that PSK was able to enhance IgM production in the human B cell line BALL-1. Furthermore, BALL-1 was shown to have the characteristic features of B-1a cells, which are independently involved in the primary immune response. These results show that there is a possibility that PSK directly acts on B cells and simultaneously enhances both humoral immunity and cellular immunity.

PMID: 18848763 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/18848763

Autoimmune Disease, Diseases, Inflammatory, Medical Studies, PSP

Polysaccharopeptide mimics ciclosporin-mediated Th1/Th2 cytokine balance for suppression of activated human T cell proliferation by MAPKp38 and STAT5 pathways.

Lee CL, Sit WH, Jiang PP, So IW, Wan JM.

School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong, SAR, China.

Abstract

The activation of T helper (Th) cell subsets plays an important role in the human immune system. Uncontrolled Th1 and Th2 responses lead to autoimmune and inflammatory diseases, respectively. The identification of agents that modulate the Th1/Th2 cytokines is therefore essential for controlling these diseases. We recently reported that polysaccharopeptide (PSP) from Coriolus versicolor exhibited ciclosporin-like activities to control aberrant T lymphocyte activation. Here, we compared the properties of PSP with ciclosporin on cell proliferation, CD25+ expression, secretion of Th1/Th2 cytokines and activation of mitogen-activated protein kinase (MAPK)p38 and signal transducers and activators of transcription 5 (STAT5) on T cells. The data show that PSP alone suppresses the proliferation of activated T cells. PSP exhibited similar and additive inhibitory effects to ciclosporin to suppress activated T cell proliferation, Th1 cytokines and reduce CD3+/CD25+ cell expression, but not Th2 cytokine expression, which helps the cytokine balance shift towards Th2 dominance. These suppressive actions of PSP involved the MAPKp38 and STAT5 pathways. These findings refine our understanding of the effects of PSP on T lymphocytes and its adjuvant properties with the immunosuppressant ciclosporin for possible control of autoimmune diseases.

PMID: 18957170 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/18957170

Immunotherapy, Medical Studies, PSP

Immunomodulatory effects of polysaccharopeptide (PSP) in human PBMC through regulation of TRAF6/TLR immunosignal-transduction pathways.

Li W, Liu M, Lai S, Xu C, Lu F, Xiao X, Bao Y.

Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Context: Polysaccharopeptide (PSP) was extracted from Coriolus versicolor, and has been proved to be a valuable adjuvant for the combination with chemotherapy or radiotherapy in the treatment of various cancers. Objective: To understand the mechanism of PSP on immunomodulation, we examined gene expression and cytokine secretion associated with immunosignal-transduction signaling in human peripheral blood mononuclear cells (PBMCs). Methods: cDNA microarray and cytokine antibody array were used to identify differential gene expression profiles and cytokines secretion of PBMCs in the presence or absence of PSP for 24 h. The expression of the key genes and proteins related to Toll-like receptor (TLR) signaling and its downstream pathway was determined by RT-PCR or Western blot. Results: Compared with the control group, PSP up-regulated 22 genes expression (such as IFN-gamma, CXCL10, TLR4, TLR5) in 117 genes associated with TLR signaling. Twenty-three of genes (e.g., TLR9, TLR10, SARM1, TOLLIP) related with TLR signaling pathway were down-regulated in PBMCs under PSP treatments. Five of cytokines (GCSF, GM-CSF, IL-1alpha, IL-6, IFN-gamma) were up-regulated more than 1.3 times by PSP. The mRNA levels of TRAM, TRIF, and TRAF6, which are the key molecules of TLR signaling pathway, were markedly increased (P < 0.05). Moreover, the protein level of TRAF6 was also markedly increased (P < 0.01). Conclusions: PSP-regulated gene expression and cytokine secretion related to TLR signaling pathway in human PBMCs. Especially, TRAM-TRIF-TRAF6 subsignaling pathway of TLR may be one of the key associated signaling pathways in the immunomodulation of PSP.

PMID: 20131955 [PubMed – as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/20131955

Cancer, Leukemia, Medical Studies, PSP

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells.

Wan JM, Sit WH, Yang X, Jiang P, Wong LL.

Agricultural, Food and Nutritional Sciences Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China. jmfwan@hkusua.hku.hk.

Abstract

ABSTRACT:

BACKGROUND: Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT).

METHODS: We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT.

RESULTS: PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT.

CONCLUSION: The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.

PMID: 20423495 [PubMed – in process]PMCID: PMC2874562

http://www.ncbi.nlm.nih.gov/pubmed/20423495