title: Antidiabetic effects of the Cimicifuga racemosa extract Ze 450 in vitro and in vivo in ob/ob mice.
abstract: BACKGROUND
  It was the aim of the present experiments to examine potential antidiabetic effects of the Cimicifuga racemosa extract Ze 450.
  
  
  METHODS
  Ze 450 and some of its components (23-epi-26-deoxyactein, protopine and cimiracemoside C) were investigated in vitro for their effects on AMP-activated protein kinase (AMPK) compared to metformin in HepaRG cells. Ze 450 (given orally (PO) and intraperitonally (IP)), metformin (PO) and controls were given over 7 days to 68 male ob/ob mice. Glucose and insulin concentrations were measured at baseline and during an oral glucose tolerance test (OGTT).
  
  
  RESULTS
  Ze 450 and its components activated AMPK to the same extent as metformin. In mice, Ze 450 (PO/IP) decreased significantly average daily and cumulative weight gain, average daily food and water intake, while metformin had no effect. In contrast to metformin, PO Ze 450 virtually did not change maximum glucose levels during OGTT, however, prolonged elimination. Ze 450 administered PO and IP decreased significantly post-stimulated insulin, whereas metformin did not. HOMA-IR index of insulin resistance improved significantly after IP and PO Ze 450 and slightly after metformin. In summary, the results demonstrate that Ze 450 reduced significantly body weight, plasma glucose, improved glucose metabolism and insulin sensitivity in diabetic ob/ob mice. In vitro experiments suggest that part of the effects may be related to AMPK activation.
  
  
  CONCLUSIONS
  Ze 450 may have utility in the treatment of type 2 diabetes. However, longer term studies in additional animal models or patients with disturbed glucose tolerance or diabetes may be of use to investigate this further.
authors.affiliation: Preclinical Research, Max Zeller Soehne AG, Romanshorn, Switzerland.
authors.forename: C
authors.initials: C
authors.lastname: Moser
authors.affiliation: RenaSci Ltd., Nottingham, UK.
authors.forename: S P
authors.initials: SP
authors.lastname: Vickers
authors.affiliation: RenaSci Ltd., Nottingham, UK.
authors.forename: R
authors.initials: R
authors.lastname: Brammer
authors.affiliation: RenaSci Ltd., Nottingham, UK.
authors.forename: S C
authors.initials: SC
authors.lastname: Cheetham
authors.affiliation: Preclinical Research, Max Zeller Soehne AG, Romanshorn, Switzerland. Electronic address: juergen.drewe@zellerag.ch.
authors.forename: J
authors.initials: J
authors.lastname: Drewe
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D001600:Berberine Alkaloids / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D002460:Cell Line; D031885:Cimicifuga / Q000737:chemistry*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004195:Disease Models, Animal; D005951:Glucose Tolerance Test; D006027:Glycosides / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000494:pharmacology; D008820:Mice, Obese; D010936:Plant Extracts / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology
chemical_list: D053119:Benzophenanthridines; D001600:Berberine Alkaloids; D001786:Blood Glucose; D006027:Glycosides; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D012503:Saponins; D014315:Triterpenes; C510722:Ze 450; C457248:23-epi-26-deoxyactein; C409563:cimiracemoside A; D008687:Metformin; D055372:AMP-Activated Protein Kinases; C009093:protopine
keywords: Cimicifuga racemosa Ze 450; Diabetes mellitus; In vitro; In vivo; ob/ob mice