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Inhibition of glucose uptake by Silybin and Dehydrosilybin
ARTICLE IN PRESS 176
Abstracts / European Journal of Integrative Medicine 1 (2009) 173–177
family sizes result in a reduced exposure to TH 1-trophic microbial stimuli from both commensals and pathogens. Observations of altered intestinal microflora in allergic children and clinical studies elucidated the role of nonpathogenic microbes of the gut and the GALT as a major factor essential for the maturation of the immune system to a nonatopic mode. A randomised, placebo-controlled pilot study of laser acupuncture and probiotics in school age children with asthma showed a beneficial clinical effect on bronchial hyperreactivity. Acupuncture treatment of patients with allergic asthma resulted in a significant decrease in Th2 cytokines IL-4, IL-6 and IL-10 serum levels. Acupuncture in allergic rhinitis leads to clinically relevant and persistent benefits. Tentatively, it appears that acupuncture and Chinese herbal medicine can be effective in allergic rhinitis and asthma, but for confirmatory evidence larger, multi-centre trials are necessary. Recently, use of paracetamol and antibiotics for common cold diseases in the first year of life and the later childhood were shown to be associated with the risk of inducing asthma, rhino-conjunctivitis and eczema. A low risk for asthma-related morbidity was also shown for ibuprofen use in febrile children. How can TCM counteract these mechanisms? Shang han lun, the oldest surviving Chinese medical text devoted to externally contracted (common) cold diseases, presents a systematized knowledge concerning the origin and development of such diseases and their treatment by highly sophisticated use of herbs combined in formulae that are skillfully modulated to deal with a vast variety of disease manifestations. Examples will be presented. Strict guidelines on diet and lifestyle are essential in TCM and will be explained. 10.1016/j.eujim.2009.09.012
Can body self development system (Body-sds) treatment prevent patients with chronic back pain from surgery? M. Heidenberg Copenhagen University, Denmark
Objective: Chronic back pain (CBP) is the most prevalent, costly and disabling musculoskeletal problem in modern western societies. We want to study if the non-pharmacotherapy and non-invasive method of Body-sds could effectively reduce the symptoms of CBP. The complementary method, Body-sds, is a manual therapy, using chiropractic, lymph drainage and massage techniques.
Methods: A pilot study will be conducted on 20 patients with indication for discusprothesis operation. The test persons will undergo 6 treatments of Body-sds, followed by an evaluation of their physical and psychological health, as well as ADL and VAS variables. There will be 3 points of evaluation: the first one, before the treatment starts and the other two, 3 and 12 months after the treatment has stopped. The patient will be asked to fill out a series of questionnaires including the Oswestry back pain scale, the SF-36, the Euro-QOL life quality scheme and the VAS scale. 10.1016/j.eujim.2009.09.013
Inhibition of glucose uptake by Silybin and Dehydrosilybin T. Zhan, M. Digel, W. Stremmel, J. Fu¨llekrug University of Heidelberg, Department of Gastroenterology, Heidelberg, Germany Type 2 diabetes (T2D) is a common disease in industrialized countries. Pathological changes in cellular glucose and fatty acid uptake are hallmarks of T2D. Medical plants from traditional medical systems of China and India are considered as a promising source for new anti-diabetic drugs. Here, we screened a panel of plant extracts and single chemical compounds from traditional medical plants with reported anti-diabetic effects for their ability to modulate cellular glucose and fatty acid uptake rates. Cellular glucose uptake, but not cellular fatty acid uptake, was significantly reduced by several candidate drugs. Of those drugs, we chose Silybin (SIL) and its derivative Dehydrosilybin (DHS), two main flavonoids of Silybum marianum, for further investigations. SIL is reported to improve blood sugar control in several clinical trials and also possesses strong anti-cancer effects. We could show that SIL and DHS inhibit glucose transport in 3T3-L1 fibroblasts and adipocytes. Both flavonoids reduce basal glucose uptake in a dosedependent manner (52% and 36% of basal uptake for 40 mM SIL, 5% and 20% of basal uptake for 40 mM DHS in fibroblasts and adipocytes). Insulin-stimulated glucose uptake is inhibited by SIL and DHS at concentrations of 20 and 10 mM, respectively. Using time course experiments, immunofluorescence microscopy and subcellular fractionation/immunoblotting, we demonstrated that both substances do not interfere with insulin-triggered translocation of GLUT4 to the plasma membrane. Onward metabolism seems unaffected since there are no inhibitory effects of SIL and DHS on hexokinase activity in 3T3-L1 adipocytes. To determine whether SIL and DHS may affect intrinsic transport activity of
ARTICLE IN PRESS Abstracts / European Journal of Integrative Medicine 1 (2009) 173–177
GLUT4, we heterologously expressed this isoform in CHO-K1 cells. CHO-K1 expressing GLUT4 shows a 2-fold increase in basal glucose uptake compared to control cells. This increase in glucose transport is completely abolished by 40 mM SIL or DHS. SIL and DHS therefore inhibit glucose uptake by interfering with glucose transporters including GLUT4. Stable expression of GLUT4 in CHO-K1 significantly reduces the cytotoxic effect of both SIL and DHS as determined by
177
MTT assay, indicating that restriction of glucose uptake is an important mechanism for the anti-cancer effect of the flavonoids. Our results show that inhibition of glucose transporters is a potential mechanism by which anti-diabetics from medical plants could work. 10.1016/j.eujim.2009.09.014
Abstracts / European Journal of Integrative Medicine 1 (2009) 173–177
family sizes result in a reduced exposure to TH 1-trophic microbial stimuli from both commensals and pathogens. Observations of altered intestinal microflora in allergic children and clinical studies elucidated the role of nonpathogenic microbes of the gut and the GALT as a major factor essential for the maturation of the immune system to a nonatopic mode. A randomised, placebo-controlled pilot study of laser acupuncture and probiotics in school age children with asthma showed a beneficial clinical effect on bronchial hyperreactivity. Acupuncture treatment of patients with allergic asthma resulted in a significant decrease in Th2 cytokines IL-4, IL-6 and IL-10 serum levels. Acupuncture in allergic rhinitis leads to clinically relevant and persistent benefits. Tentatively, it appears that acupuncture and Chinese herbal medicine can be effective in allergic rhinitis and asthma, but for confirmatory evidence larger, multi-centre trials are necessary. Recently, use of paracetamol and antibiotics for common cold diseases in the first year of life and the later childhood were shown to be associated with the risk of inducing asthma, rhino-conjunctivitis and eczema. A low risk for asthma-related morbidity was also shown for ibuprofen use in febrile children. How can TCM counteract these mechanisms? Shang han lun, the oldest surviving Chinese medical text devoted to externally contracted (common) cold diseases, presents a systematized knowledge concerning the origin and development of such diseases and their treatment by highly sophisticated use of herbs combined in formulae that are skillfully modulated to deal with a vast variety of disease manifestations. Examples will be presented. Strict guidelines on diet and lifestyle are essential in TCM and will be explained. 10.1016/j.eujim.2009.09.012
Can body self development system (Body-sds) treatment prevent patients with chronic back pain from surgery? M. Heidenberg Copenhagen University, Denmark
Objective: Chronic back pain (CBP) is the most prevalent, costly and disabling musculoskeletal problem in modern western societies. We want to study if the non-pharmacotherapy and non-invasive method of Body-sds could effectively reduce the symptoms of CBP. The complementary method, Body-sds, is a manual therapy, using chiropractic, lymph drainage and massage techniques.
Methods: A pilot study will be conducted on 20 patients with indication for discusprothesis operation. The test persons will undergo 6 treatments of Body-sds, followed by an evaluation of their physical and psychological health, as well as ADL and VAS variables. There will be 3 points of evaluation: the first one, before the treatment starts and the other two, 3 and 12 months after the treatment has stopped. The patient will be asked to fill out a series of questionnaires including the Oswestry back pain scale, the SF-36, the Euro-QOL life quality scheme and the VAS scale. 10.1016/j.eujim.2009.09.013
Inhibition of glucose uptake by Silybin and Dehydrosilybin T. Zhan, M. Digel, W. Stremmel, J. Fu¨llekrug University of Heidelberg, Department of Gastroenterology, Heidelberg, Germany Type 2 diabetes (T2D) is a common disease in industrialized countries. Pathological changes in cellular glucose and fatty acid uptake are hallmarks of T2D. Medical plants from traditional medical systems of China and India are considered as a promising source for new anti-diabetic drugs. Here, we screened a panel of plant extracts and single chemical compounds from traditional medical plants with reported anti-diabetic effects for their ability to modulate cellular glucose and fatty acid uptake rates. Cellular glucose uptake, but not cellular fatty acid uptake, was significantly reduced by several candidate drugs. Of those drugs, we chose Silybin (SIL) and its derivative Dehydrosilybin (DHS), two main flavonoids of Silybum marianum, for further investigations. SIL is reported to improve blood sugar control in several clinical trials and also possesses strong anti-cancer effects. We could show that SIL and DHS inhibit glucose transport in 3T3-L1 fibroblasts and adipocytes. Both flavonoids reduce basal glucose uptake in a dosedependent manner (52% and 36% of basal uptake for 40 mM SIL, 5% and 20% of basal uptake for 40 mM DHS in fibroblasts and adipocytes). Insulin-stimulated glucose uptake is inhibited by SIL and DHS at concentrations of 20 and 10 mM, respectively. Using time course experiments, immunofluorescence microscopy and subcellular fractionation/immunoblotting, we demonstrated that both substances do not interfere with insulin-triggered translocation of GLUT4 to the plasma membrane. Onward metabolism seems unaffected since there are no inhibitory effects of SIL and DHS on hexokinase activity in 3T3-L1 adipocytes. To determine whether SIL and DHS may affect intrinsic transport activity of
ARTICLE IN PRESS Abstracts / European Journal of Integrative Medicine 1 (2009) 173–177
GLUT4, we heterologously expressed this isoform in CHO-K1 cells. CHO-K1 expressing GLUT4 shows a 2-fold increase in basal glucose uptake compared to control cells. This increase in glucose transport is completely abolished by 40 mM SIL or DHS. SIL and DHS therefore inhibit glucose uptake by interfering with glucose transporters including GLUT4. Stable expression of GLUT4 in CHO-K1 significantly reduces the cytotoxic effect of both SIL and DHS as determined by
177
MTT assay, indicating that restriction of glucose uptake is an important mechanism for the anti-cancer effect of the flavonoids. Our results show that inhibition of glucose transporters is a potential mechanism by which anti-diabetics from medical plants could work. 10.1016/j.eujim.2009.09.014