The Experts below are selected from a list of 174 Experts worldwide ranked by ideXlab platform

S.t. Chang - One of the best experts on this subject based on the ideXlab platform.

H.-x. Wang - One of the best experts on this subject based on the ideXlab platform.

John H K Yeung - One of the best experts on this subject based on the ideXlab platform.

  • Polysaccharide Peptides from coriolus versicolor competitively inhibit model cytochrome p450 enzyme probe substrates metabolism in human liver microsomes
    Phytomedicine, 2012
    Co-Authors: John H K Yeung
    Abstract:

    Abstract Polysaccharide Peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy or health supplement in China. Previous studies have shown that PSP decreased antipyrine clearance and inhibited rat CYP2C11-mediated tolbutamide 4-hydroxylation and in human CYP2C9. In this study, the effects of the water extractable fraction of PSP on the metabolism of model CYP1A2, CYP2D6, CYP2E1 and CYP3A4 probe substrates were investigated in pooled human liver microsomes. PSP (1.25–20 μM) dose-dependently decreased CYP1A2-mediated metabolism of phenacetin to paracetamol (IC50 19.7 μM) and CYP3A4-mediated metabolism of testosterone to 6β-hydroxytestosterone (IC20 7.06 μM). Enzyme kinetics studies showed the inhibition of CYP1A2 activity was competitive and concentration-dependent (Ki = 18.4 μM). Inhibition of testosterone to 6β-hydroxytestosterone was also competitive and concentration-dependent (Ki = 31.8 μM). Metabolism of dextromethorphan to dextrorphan (CYP2D6-mediated) and chlorzoxazone to 6-hydroxychlorzoxazone (CYP2E1-mediated) was only minimally inhibited by PSP, with IC20 values at 15.6 μM and 11.9 μM, respectively. This study demonstrated that PSP competitively inhibited the CYP1A2- and CYP3A4-mediated metabolism of model probe substrates in human liver microsomes in vitro. The relatively high Ki values for CYP1A2 and CYP3A4 would suggest a low potential for PSP to cause herb–drug interaction related to these CYP isoforms.

  • modulation of antipyrine clearance by Polysaccharide Peptide psp isolated from coriolus versicolor in the rat
    Food and Chemical Toxicology, 2006
    Co-Authors: Siulung Chan, John H K Yeung
    Abstract:

    Abstract Polysaccharide Peptide (PSP), isolated from Coriolus versicolor COV-1 , has been previously shown to have immuno-stimulatory, anti-tumour and analgesic effects in animal models. When used as an adjunct in cancer chemotherapy in clinical trials carried out in China, PSP improved the quality of life in the patients by improving appetite and alleviating symptoms associated with cancer chemotherapy. In this study, the effects of non-toxic doses of PSP on phase I metabolism was investigated in the rat, using the conventional probe antipyrine. Acute PSP (3–5 μmol/kg, i.p.) treatment did not produce significant changes in antipyrine clearance. Sub-chronic treatment with PSP (1–3 μmol/kg/day, i.p., 3 days) decreased the antipyrine clearance (30–35%), with an increase in the plasma half-life ( T 1/2 ) by 55% and an increase in the area under concentration–time curve (AUC) by 61%. Total hepatic cytochrome P450 (P450) was dose-dependently decreased (32–54%) after sub-chronic, but not the acute treatment of PSP. Given that PSP can affect phase I metabolism and hepatic cytochrome P450 content, the concomitant use of PSP with other therapeutic agents that undergo phase I metabolism should be carefully monitored.

  • Polysaccharide Peptides from cov 1 strain of coriolus versicolor inhibit tolbutamide 4 hydroxylation in the rat in vitro and in vivo
    Food and Chemical Toxicology, 2006
    Co-Authors: John H K Yeung, Siulung Chan
    Abstract:

    Polysaccharide Peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy in China. In this study, the effects of whole PSP extract and water extract of PSP on 4-hydroxylation of tolbutamide were investigated in rat liver microsomes in vitro and in vivo in the rat. Both the whole PSP extract and the water soluble fraction (0.5-20 microM) decreased the metabolism of tolbutamide to 4-hydroxytolbutamide in vitro. Enzyme kinetics studies showed that PSP inhibited tolbutamide 4-hydroxylase activity in a competitive, concentration-dependent manner. The whole PSP extract had a Ki value of 12.6 microM and IC50 at 18.4 microM, while the water extract had a Ki value of 6.9 microM and IC50 at 9.8 microM. Sulphaphenazole, a specific human CYP2C9 inhibitor, showed a Ki value of 30.8 microM and IC50 at 44.0 microM in the test system. In the pharmacokinetic studies in vivo, acute PSP (4 micromol/kg, i.p.) treatment did not produce significant changes in tolbutamide clearance, but produced a decrease in the Cinitial (7.4%) and an increase in the Vd (7.4%). Sub-chronic pre-treatment of PSP (1-2 micromol/kg/day, i.p.) for three days did not affect the clearance and AUC of tolbutamide, but the Cinitial was decreased, together with increases in the T1/2, and Vd. The formation of 4-hydroxytolbutamide in vivo was decreased in both acute and sub-chronic studies. Taken together, this study demonstrated the PSP can inhibit tolbutamide 4-hydroxylation both in vitro and in vivo. Despite the fact that CYP isoforms that metabolise tolbutamide are different between rat and human liver due to different catalytic characteristics, and rat studies may not be directly extrapolatable to man, the concomitant use of PSP with other CYP2C substrates should be carefully monitored.

  • effects of Polysaccharide Peptide psp from coriolus versicolor on the pharmacokinetics of cyclophosphamide in the rat and cytotoxicity in hepg2 cells
    Food and Chemical Toxicology, 2006
    Co-Authors: Siulung Chan, John H K Yeung
    Abstract:

    Polysaccharide Peptide (PSP), isolated from Coriolus versicolor COV-1, has been shown to restore the immunological effects against cyclophosphamide-induced immuno-suppression, although the mechanism(s) involved remain uncertain. This study investigated the PSP-cyclophosphamide interaction by studying the effects of PSP on the pharmacokinetic of cyclophosphamide in the rat and the effect of PSP on the cytotoxic effects of cyclophosphamide on a cancer cell line (HepG2 cells). In the pharmacokinetic studies in the rat, acute pre-treatment of PSP (4 micromol/kg/day, i.p.) decreased the clearance (CL) of cyclophosphamide by 31%, with a concomitant increase in the area under concentration-time curve (AUC) by 44%, and prolongation of the plasma half-life (T(1/2)) by 43%. Sub-chronic pre-treatment of PSP (2 micromol/kg/day, i.p., 3 days) decreased the CL of cyclophosphamide by 33%, with a concomitant increase in the AUC by 50%, and prolongation of the plasma T(1/2) by 34%. In cytotoxicity studies using HepG2 cells, non-toxic dose of PSP (1-10 microM) enhanced the cytotoxicity of cyclophosphamide. PSP at 10 microM further decreased HepG2 cell viability by 22% compared to when cyclophosphamide was present alone. In summary, PSP enhanced the cytotoxic effect of cyclophosphamide on a cancer cell line in vitro and altered the pharmacokinetics of cyclophosphamide in vivo in the rat. Both of these effects may be beneficial in the use of PSP as an adjunct to cyclophosphamide treatment.

  • Polysaccharide Peptides from cov 1 strain of coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse
    Life Sciences, 2006
    Co-Authors: Siulung Chan, John H K Yeung
    Abstract:

    Abstract Polysaccharide Peptide (PSP), isolated from Coriolus versicolor COV-1 , has been widely used as an adjunct to cancer chemotherapy and as an immuno-stimulator in China. In this study, the anti-nociceptive effects of PSP were investigated in two different pain models in the mouse. In the acetic acid-induced writhing model, initial studies showed that PSP decreased the number of acetic acid-induced writhing by 92.9%, which, by definition, would constitute an analgesic effect. However, further studies showed that PSP itself induced a dose-dependent writhing response. Studies on inflammatory mediator release showed that PSP increased the release of prostaglandin E 2 , tumor necrosis factor-α, interleukin-1β, and histamine in mouse peritoneal macrophages and mast cells both in vitro and in vivo. The role of inflammatory mediator release in PSP-induced writhing was confirmed when diclofenac and dexamethasone decreased the number of writhing responses by 54% and 58.5%, respectively. Diphenhydramine totally inhibited the PSP-induced writhing. In the hot-plate test, PSP dose-dependently shortened the hind paw withdrawal latency, indicative of a hyperalgesic effect. The hyperalgesic effect was reduced by pretreatment with the anti-inflammatory drugs. In conclusion, the PSP-induced hyperalgesia was related to activation of peritoneal resident cells and an increase in the release of inflammatory mediators.

Siulung Chan - One of the best experts on this subject based on the ideXlab platform.

  • modulation of antipyrine clearance by Polysaccharide Peptide psp isolated from coriolus versicolor in the rat
    Food and Chemical Toxicology, 2006
    Co-Authors: Siulung Chan, John H K Yeung
    Abstract:

    Abstract Polysaccharide Peptide (PSP), isolated from Coriolus versicolor COV-1 , has been previously shown to have immuno-stimulatory, anti-tumour and analgesic effects in animal models. When used as an adjunct in cancer chemotherapy in clinical trials carried out in China, PSP improved the quality of life in the patients by improving appetite and alleviating symptoms associated with cancer chemotherapy. In this study, the effects of non-toxic doses of PSP on phase I metabolism was investigated in the rat, using the conventional probe antipyrine. Acute PSP (3–5 μmol/kg, i.p.) treatment did not produce significant changes in antipyrine clearance. Sub-chronic treatment with PSP (1–3 μmol/kg/day, i.p., 3 days) decreased the antipyrine clearance (30–35%), with an increase in the plasma half-life ( T 1/2 ) by 55% and an increase in the area under concentration–time curve (AUC) by 61%. Total hepatic cytochrome P450 (P450) was dose-dependently decreased (32–54%) after sub-chronic, but not the acute treatment of PSP. Given that PSP can affect phase I metabolism and hepatic cytochrome P450 content, the concomitant use of PSP with other therapeutic agents that undergo phase I metabolism should be carefully monitored.

  • Polysaccharide Peptides from cov 1 strain of coriolus versicolor inhibit tolbutamide 4 hydroxylation in the rat in vitro and in vivo
    Food and Chemical Toxicology, 2006
    Co-Authors: John H K Yeung, Siulung Chan
    Abstract:

    Polysaccharide Peptide (PSP), isolated from COV-1 strain of Coriolus versicolor, is commonly used as an adjunct in cancer chemotherapy in China. In this study, the effects of whole PSP extract and water extract of PSP on 4-hydroxylation of tolbutamide were investigated in rat liver microsomes in vitro and in vivo in the rat. Both the whole PSP extract and the water soluble fraction (0.5-20 microM) decreased the metabolism of tolbutamide to 4-hydroxytolbutamide in vitro. Enzyme kinetics studies showed that PSP inhibited tolbutamide 4-hydroxylase activity in a competitive, concentration-dependent manner. The whole PSP extract had a Ki value of 12.6 microM and IC50 at 18.4 microM, while the water extract had a Ki value of 6.9 microM and IC50 at 9.8 microM. Sulphaphenazole, a specific human CYP2C9 inhibitor, showed a Ki value of 30.8 microM and IC50 at 44.0 microM in the test system. In the pharmacokinetic studies in vivo, acute PSP (4 micromol/kg, i.p.) treatment did not produce significant changes in tolbutamide clearance, but produced a decrease in the Cinitial (7.4%) and an increase in the Vd (7.4%). Sub-chronic pre-treatment of PSP (1-2 micromol/kg/day, i.p.) for three days did not affect the clearance and AUC of tolbutamide, but the Cinitial was decreased, together with increases in the T1/2, and Vd. The formation of 4-hydroxytolbutamide in vivo was decreased in both acute and sub-chronic studies. Taken together, this study demonstrated the PSP can inhibit tolbutamide 4-hydroxylation both in vitro and in vivo. Despite the fact that CYP isoforms that metabolise tolbutamide are different between rat and human liver due to different catalytic characteristics, and rat studies may not be directly extrapolatable to man, the concomitant use of PSP with other CYP2C substrates should be carefully monitored.

  • effects of Polysaccharide Peptide psp from coriolus versicolor on the pharmacokinetics of cyclophosphamide in the rat and cytotoxicity in hepg2 cells
    Food and Chemical Toxicology, 2006
    Co-Authors: Siulung Chan, John H K Yeung
    Abstract:

    Polysaccharide Peptide (PSP), isolated from Coriolus versicolor COV-1, has been shown to restore the immunological effects against cyclophosphamide-induced immuno-suppression, although the mechanism(s) involved remain uncertain. This study investigated the PSP-cyclophosphamide interaction by studying the effects of PSP on the pharmacokinetic of cyclophosphamide in the rat and the effect of PSP on the cytotoxic effects of cyclophosphamide on a cancer cell line (HepG2 cells). In the pharmacokinetic studies in the rat, acute pre-treatment of PSP (4 micromol/kg/day, i.p.) decreased the clearance (CL) of cyclophosphamide by 31%, with a concomitant increase in the area under concentration-time curve (AUC) by 44%, and prolongation of the plasma half-life (T(1/2)) by 43%. Sub-chronic pre-treatment of PSP (2 micromol/kg/day, i.p., 3 days) decreased the CL of cyclophosphamide by 33%, with a concomitant increase in the AUC by 50%, and prolongation of the plasma T(1/2) by 34%. In cytotoxicity studies using HepG2 cells, non-toxic dose of PSP (1-10 microM) enhanced the cytotoxicity of cyclophosphamide. PSP at 10 microM further decreased HepG2 cell viability by 22% compared to when cyclophosphamide was present alone. In summary, PSP enhanced the cytotoxic effect of cyclophosphamide on a cancer cell line in vitro and altered the pharmacokinetics of cyclophosphamide in vivo in the rat. Both of these effects may be beneficial in the use of PSP as an adjunct to cyclophosphamide treatment.

  • Polysaccharide Peptides from cov 1 strain of coriolus versicolor induce hyperalgesia via inflammatory mediator release in the mouse
    Life Sciences, 2006
    Co-Authors: Siulung Chan, John H K Yeung
    Abstract:

    Abstract Polysaccharide Peptide (PSP), isolated from Coriolus versicolor COV-1 , has been widely used as an adjunct to cancer chemotherapy and as an immuno-stimulator in China. In this study, the anti-nociceptive effects of PSP were investigated in two different pain models in the mouse. In the acetic acid-induced writhing model, initial studies showed that PSP decreased the number of acetic acid-induced writhing by 92.9%, which, by definition, would constitute an analgesic effect. However, further studies showed that PSP itself induced a dose-dependent writhing response. Studies on inflammatory mediator release showed that PSP increased the release of prostaglandin E 2 , tumor necrosis factor-α, interleukin-1β, and histamine in mouse peritoneal macrophages and mast cells both in vitro and in vivo. The role of inflammatory mediator release in PSP-induced writhing was confirmed when diclofenac and dexamethasone decreased the number of writhing responses by 54% and 58.5%, respectively. Diphenhydramine totally inhibited the PSP-induced writhing. In the hot-plate test, PSP dose-dependently shortened the hind paw withdrawal latency, indicative of a hyperalgesic effect. The hyperalgesic effect was reduced by pretreatment with the anti-inflammatory drugs. In conclusion, the PSP-induced hyperalgesia was related to activation of peritoneal resident cells and an increase in the release of inflammatory mediators.

Jong Won Yun - One of the best experts on this subject based on the ideXlab platform.

  • apoptosis of human hepatocarcinoma hepg2 and neuroblastoma skn sh cells induced by Polysaccharides Peptide complexes produced by submerged mycelial culture of an entomopathogenic fungus cordyceps sphecocephala
    Journal of Microbiology and Biotechnology, 2008
    Co-Authors: Yu Mi Baek, Sang Woo Kim, Hye Jin Hwang, Hee Sun Hwang, Sung Hak Lee, Jong Won Yun
    Abstract:

    Three different Polysaccharide-Peptide complexes (PPC, named as Fr-I, Fr-II, and Fr-III) were produced by submerged mycelial culture of an entomopathogenic fungus Cordyceps sphecocephala, and their anticancer activities were investigated in human hepatocarcinoma (HepG2) and neuroblastoma (SK-N-SH) cells. The highest inhibitory effects of PPC on both HepG2 and SK-N-SH cells were achieved with Fr-I, whereas Fr-III with low molecular mass showed lower inhibition effects. Interestingly, the inhibitory effects of the three fractions were increased after protease digestion, suggesting that the inhibitory effects resulted mainly from the carbohydrate moiety, at least in the case of Fr-II and Fr-III, of PPC. The results of DNA fragmentation in PPC-induced apoptotic cells were confirmed by both DNA ladder assay and comet assay. Our investigation also showed that PPC-induced apoptosis of both cancer cells was associated with intracellular events including DNA fragmentation, activation of caspase-3, and modulation of Bcl-2 and Bax. We conclude that PPC has potential as a novel therapeutic agent for the treatment of both HepG2 and SK-N-SH cancer cells without any cytotoxicity against normal cells.

  • production of Polysaccharide Peptide complexes by submerged mycelial culture of an entomopathogenic fungus cordyceps sphecocephala
    Process Biochemistry, 2007
    Co-Authors: Eunjae Cho, Sunghee Nam, Jangwon Choi, Jong Won Yun
    Abstract:

    Abstract The effects of medium components and environmental factors on the production of mycelial biomass and PolysaccharidePeptide complexes (exobiopolymers) by Cordyceps sphecocephala J-201 were investigated in submerged cultures. The optimal temperature and initial pH for the production of both mycelial biomass and exobiopolymers in flask cultures were found to be 25 °C and pH 4–5, respectively. The optimal combination of the media constituents was as follows (g l−1): sucrose 40, yeast extract 6, polypepton 2, KH2PO4 0.46, K2HPO4 1, and MgSO4·7H2O 0.5. The results of bioreactor culture revealed that the maximum concentration of mycelial biomass (28.2 g l−1) was obtained at an agitation speed of 300 rpm and at an aeration rate of 2 vvm, whereas maximum exobiopolymer production (2.5 g l−1) was achieved at a milder agitation speed (150 rpm). There was a significant variance in mycelial morphology between different aeration conditions. Looser mycelial pellets were developed, and their size and hairiness increased as the aeration rate increased from 0.5 to 2.0 vvm, resulting in enhanced exobiopolymer production. The apparent viscosities of fermentation broth increased rapidly towards the end of fermentations at the conditions of high aeration rate and agitation speed, which were mainly due to high amount of mycelial biomass rather than exobiopolymers at the later stages of fermentation. The three different exobiopolymers (FR-I, -II, and -III) were fractionated by a gel filtration chromatography on Sepharose CL-6B. The carbohydrate and protein contents in each fraction were significantly different and the molecular weights of FR-I, FR-II, and FR-III were determined to be 1831, 27, and 2.2 kDa, respectively. The compositional analysis revealed that the three fractions of crude exobiopolymers consisted of acidic and nonpolar amino acids, such as aspartic acid, glutamic acid, glycine, and valine in protein moiety, and of mainly mannose and galactose in sugar moiety.