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Influence of an anti-diabetic foot ulcer formula and its component herbs on tissue and systemic glucose homeostasis
Authors:Chan C M  Chan Y W  Lau C H  Lau T W  Lau K M  Lam F C  Che C T  Leung P C  Fung K P  Lau C B S  Ho Y Y
Institution:Department of Biochemistry, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Abstract:Complications of diabetes impose major public health burdens worldwide. The positive effect of a Radix Astragali-based herbal preparation on healing diabetic foot ulcers in patients has been reported. Formula 1 is also referred as the 'Herbal drink to strengthen muscle and control swelling'. This formula contains six Chinese medical herbs, including Radix Astragali, Radix Rehmanniae, Rhizoma Smilacis Chinensis, Rhizoma Atractylodis Macrocephalae, Radix Polygoni Multiflori Preparata, and Radix Stephania Tetrandrae. Three of these herbs (Radix Astragali, Radix Rehmanniae, Rhizoma Atractylodis Macrocephalae) are commonly used in different anti-diabetic formulae of Chinese medicine. The objective of the current study is to use an interdisciplinary approach to test the hypothesis that Formula 1 and its components influence tissue and systemic glucose homeostasis. In vitro and in vivo models have been established including: (1) glucose absorption into intestinal brush border membrane vesicles (BBMV); (2) gluconeogenesis by H4IIE hepatoma cells; (3) glucose uptake by 3T3-L1 adipocytes and Hs68 skin fibroblasts; (4) normalization of glycaemic control in a diabetic rat model. The results of in vitro studies indicated that all herbal extracts can modify cellular glucose homeostasis. Since Formula 1 and Rhizoma Smilacis Chinensis extracts demonstrated potent effects on modifying glucose homeostasis in multiple tissues in vitro, they were further studied for their anti-diabetic activities in vivo using a streptozotocin (STZ)-induced diabetic rat model. The results showed that Formula 1 and Rhizoma Smilacis Chinensis extracts did not significantly improve oral glucose tolerance or basal glycaemia in diabetic rats. In conclusion, the anti-diabetic foot ulcer Formula 1 contains ingredients active in modifying tissue glucose homeostasis in vitro but these biological activities could not be associated with improved glycaemic control of diabetes in vivo.
Keywords:2-DG  2-deoxy-d-glucose  ATCC  American Type Culture Collection  AUC  area under the curve  BBMV  brush border membrane vesicles  BCA  bicinchoninic acid  DEX  dexamethasone  DMEM  Dulbecco's modified Eagle medium  DTT  dithiothreitol  EDTA  ethylenediaminetetraacetic acid  FBS  fetal bovine serum  G6Pase  glucose-6-phosphatase  GDP  guanosine 5′-diphosphate  HEPES  N-2-hydroxyethylpiperazine-N′-2-ethanesulphonic acid  IBMX  3-isobutyl-1-methylxanthine  NADH  nicotinamide adenine dinucleotide (reduced form)  PBS  phosphate-buffered saline  pCPT-cAMP  8-(4-chlorophenylthio)-cAMP  PEPCK  phosphoenolpyruvate carboxykinase  STZ  streptozotocin  TCM  traditional Chinese medicine  Tris  tris(hydroxymethyl)aminomethane  v/v  volume by volume  w/w  weight by weight
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