The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform

David R Rose - One of the best experts on this subject based on the ideXlab platform.

  • new glucosidase inhibitors from an ayurvedic Herbal Treatment for type 2 diabetes structures and inhibition of human intestinal maltase glucoamylase with compounds from salacia reticulata
    Biochemistry, 2010
    Co-Authors: Kumarasamy Jayakanthan, Sankar Mohan, Ravindranath Nasi, Blair D Johnston, B M Pinto, David R Rose
    Abstract:

    An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target α-amylases and intestinal glucosidases using α-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of α-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the Treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (Ki = 0.03 μM), some 2000-fold better than the compounds currently used in the clinic, and highlights the poten...

  • New glucosidase inhibitors from an ayurvedic Herbal Treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata.
    Biochemistry, 2010
    Co-Authors: Lyann Sim, Kumarasamy Jayakanthan, Sankar Mohan, Ravindranath Nasi, Blair D Johnston, B M Pinto, David R Rose
    Abstract:

    An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target alpha-amylases and intestinal glucosidases using alpha-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of alpha-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the Treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (K(i) = 0.03 microM), some 2000-fold better than the compounds currently used in the clinic, and highlights the potential of the salacinol class of inhibitors as future drug candidates.

Gustav Dobos - One of the best experts on this subject based on the ideXlab platform.

  • distinct kinetics in the frequency of peripheral cd4 t cells in patients with ulcerative colitis experiencing a flare during Treatment with mesalazine or with a Herbal preparation of myrrh chamomile and coffee charcoal
    PLOS ONE, 2014
    Co-Authors: Jost Langhorst, Gustav Dobos, Annika Frede, Markus Knott, Eva Pastille, Jan Buer, Astrid M Westendorf
    Abstract:

    Background: We found the first evidence of the efficacy of a Herbal Treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the Herbal Treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood. Aim: To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC. Methods: Patients in clinical remission were treated with either mesalazine or the Herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare. Results: A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two Treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either Treatment. In contrast, CD4+ T cells, CD4+CD25med effector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the Herbal Treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare. Conclusions: In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during Treatment with myrrh, chamomile extract, and coffee charcoal than during Treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease. Trial registration: EU Clinical Trials Register 2007-007928-18/DE.

  • randomised clinical trial a Herbal preparation of myrrh chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis a double blind double dummy study
    Alimentary Pharmacology & Therapeutics, 2013
    Co-Authors: Jost Langhorst, I Varnhagen, S Schneider, U Albrecht, Andreas Rueffer, Rainer Stange, Andreas Michalsen, Gustav Dobos
    Abstract:

    Summary Background The Herbal Treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard Treatment for maintaining remission in ulcerative colitis (UC). Aim To compare the efficacy of the two Treatments in maintaining remission in patients with ulcerative colitis. Methods We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the Herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. Results A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two Treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine Treatment group and 25/47 patients (53%) in the Herbal Treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. Conclusions The Herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18.

Jost Langhorst - One of the best experts on this subject based on the ideXlab platform.

  • distinct kinetics in the frequency of peripheral cd4 t cells in patients with ulcerative colitis experiencing a flare during Treatment with mesalazine or with a Herbal preparation of myrrh chamomile and coffee charcoal
    PLOS ONE, 2014
    Co-Authors: Jost Langhorst, Gustav Dobos, Annika Frede, Markus Knott, Eva Pastille, Jan Buer, Astrid M Westendorf
    Abstract:

    Background: We found the first evidence of the efficacy of a Herbal Treatment with myrrh, dry extract of chamomile flowers, and coffee charcoal for ulcerative colitis (UC). However, the impact of the Herbal Treatment on the CD4+ T-cell compartment, which is essential for both the induction of UC and the maintenance of tolerance in the gut, is not well understood. Aim: To analyze the frequency and functional phenotype of CD4+ T cells and of immune-suppressive CD4+CD25high regulatory T cells (Tregs) in healthy control subjects, patients with UC in remission, and patients with clinical flare of UC. Methods: Patients in clinical remission were treated with either mesalazine or the Herbal preparation for 12 months. The frequencies of whole CD4+ T cells, CD4+CD25med effector T cells, and Tregs and the expression of Foxp3 within the CD4+CD25hig Tregs were determined by flow cytometry at 6 time points. We determined the suppressive capability of Tregs from healthy control subjects and from patients in remission or clinical flare. Results: A total of 79 patients (42 women, 37 men; mean age, 48.5 years; 38 with clinical flare) and 5 healthy control subjects were included in the study. At baseline the frequencies of whole CD4+ T cells, CD4+CD25med effector cells, and Tregs did not differ between the two Treatment groups and the healthy control subjects. In addition, patients with UC in sustained clinical remission showed no alteration from baseline after 1, 3, 6, 9, or 12 months of either Treatment. In contrast, CD4+ T cells, CD4+CD25med effector T cells, and Tregs demonstrated distinctly different patterns at time points pre-flare and flare. The mesalazine group showed a continuous but not statistically significant increase from baseline to pre-flare and flare (p = ns). In the Herbal Treatment group, however, the percentage of the CD4+ T cells was lower at pre-flare than at baseline. This decrease was completely reversed after flare, when a significant increase was seen (CD4+CD25med pre-flare/flare p = 0.0461; CD4+CD25high baseline/flare p = 0.0269 and pre-flare/flare p = 0.0032). In contrast, no changes in the expression of Foxp3 cells were detected within the subsets of CD4+CD25high regulatory T cells. Of note, no alterations were detected in the suppressive capability of CD4+CD25high regulatory T cells isolated from the peripheral blood of healthy donors, from patients in remission, or from patients with clinical flare. Conclusions: In patients with UC experiencing acute flare, the CD4+ T compartment demonstrates a distinctly different pattern during Treatment with myrrh, chamomile extract, and coffee charcoal than during Treatment with mesalazine. These findings suggest an active repopulation of regulatory T cells during active disease. Trial registration: EU Clinical Trials Register 2007-007928-18/DE.

  • randomised clinical trial a Herbal preparation of myrrh chamomile and coffee charcoal compared with mesalazine in maintaining remission in ulcerative colitis a double blind double dummy study
    Alimentary Pharmacology & Therapeutics, 2013
    Co-Authors: Jost Langhorst, I Varnhagen, S Schneider, U Albrecht, Andreas Rueffer, Rainer Stange, Andreas Michalsen, Gustav Dobos
    Abstract:

    Summary Background The Herbal Treatment with myrrh, dry extract of chamomile flowers and coffee charcoal has anti-inflammatory and antidiarrhoeal potential and might benefit patients with UC. Aminosalicylates are used as standard Treatment for maintaining remission in ulcerative colitis (UC). Aim To compare the efficacy of the two Treatments in maintaining remission in patients with ulcerative colitis. Methods We performed a randomised, double-blind, double-dummy study over a 12-month period in patients with UC. Primary endpoint was non-inferiority of the Herbal preparation as defined by mean Clinical Colitis Activity Index (CAI-Rachmilewitz). Secondary endpoints were relapse rates, safety profile, relapse-free times, endoscopic activity and faecal biomarkers. Results A total of 96 patients (51 female) with inactive UC were included. Mean CAI demonstrated no significant difference between the two Treatment groups in the intention-to-treat (P = 0.121) or per-protocol (P = 0.251) analysis. Relapse rates in total were 22/49 patients (45%) in the mesalazine Treatment group and 25/47 patients (53%) in the Herbal Treatment group (P = 0.540). Safety profile and tolerability were good and no significant differences were shown in relapse-free time, endoscopy and faecal biomarkers. Conclusions The Herbal preparation of myrrh, chamomile extract and coffee charcoal is well tolerated and shows a good safety profile. We found first evidence for a potential efficacy non-inferior to the gold standard therapy mesalazine, which merits further study of its clinical usefulness in maintenance therapy of patients with ulcerative colitis. EudraCT-Number 2007-007928-18.

Kumarasamy Jayakanthan - One of the best experts on this subject based on the ideXlab platform.

  • new glucosidase inhibitors from an ayurvedic Herbal Treatment for type 2 diabetes structures and inhibition of human intestinal maltase glucoamylase with compounds from salacia reticulata
    Biochemistry, 2010
    Co-Authors: Kumarasamy Jayakanthan, Sankar Mohan, Ravindranath Nasi, Blair D Johnston, B M Pinto, David R Rose
    Abstract:

    An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target α-amylases and intestinal glucosidases using α-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of α-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the Treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (Ki = 0.03 μM), some 2000-fold better than the compounds currently used in the clinic, and highlights the poten...

  • New glucosidase inhibitors from an ayurvedic Herbal Treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata.
    Biochemistry, 2010
    Co-Authors: Lyann Sim, Kumarasamy Jayakanthan, Sankar Mohan, Ravindranath Nasi, Blair D Johnston, B M Pinto, David R Rose
    Abstract:

    An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target alpha-amylases and intestinal glucosidases using alpha-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of alpha-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the Treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (K(i) = 0.03 microM), some 2000-fold better than the compounds currently used in the clinic, and highlights the potential of the salacinol class of inhibitors as future drug candidates.

B M Pinto - One of the best experts on this subject based on the ideXlab platform.

  • new glucosidase inhibitors from an ayurvedic Herbal Treatment for type 2 diabetes structures and inhibition of human intestinal maltase glucoamylase with compounds from salacia reticulata
    Biochemistry, 2010
    Co-Authors: Kumarasamy Jayakanthan, Sankar Mohan, Ravindranath Nasi, Blair D Johnston, B M Pinto, David R Rose
    Abstract:

    An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target α-amylases and intestinal glucosidases using α-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of α-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the Treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (Ki = 0.03 μM), some 2000-fold better than the compounds currently used in the clinic, and highlights the poten...

  • New glucosidase inhibitors from an ayurvedic Herbal Treatment for type 2 diabetes: structures and inhibition of human intestinal maltase-glucoamylase with compounds from Salacia reticulata.
    Biochemistry, 2010
    Co-Authors: Lyann Sim, Kumarasamy Jayakanthan, Sankar Mohan, Ravindranath Nasi, Blair D Johnston, B M Pinto, David R Rose
    Abstract:

    An approach to controlling blood glucose levels in individuals with type 2 diabetes is to target alpha-amylases and intestinal glucosidases using alpha-glucosidase inhibitors acarbose and miglitol. One of the intestinal glucosidases targeted is the N-terminal catalytic domain of maltase-glucoamylase (ntMGAM), one of the four intestinal glycoside hydrolase 31 enzyme activities responsible for the hydrolysis of terminal starch products into glucose. Here we present the X-ray crystallographic studies of ntMGAM in complex with a new class of alpha-glucosidase inhibitors derived from natural extracts of Salacia reticulata, a plant used traditionally in Ayuverdic medicine for the Treatment of type 2 diabetes. Included in these extracts are the active compounds salacinol, kotalanol, and de-O-sulfonated kotalanol. This study reveals that de-O-sulfonated kotalanol is the most potent ntMGAM inhibitor reported to date (K(i) = 0.03 microM), some 2000-fold better than the compounds currently used in the clinic, and highlights the potential of the salacinol class of inhibitors as future drug candidates.