title: Antidiabetic effects of chamomile flowers extract in obese mice through transcriptional stimulation of nutrient sensors of the peroxisome proliferator-activated receptor (PPAR) family.
abstract: Given the significant increases in the incidence of metabolic diseases, efficient strategies for preventing and treating of these common disorders are urgently needed. This includes the development of phytopharmaceutical products or functional foods to prevent or cure metabolic diseases. Plant extracts from edible biomaterial provide a potential resource of structurally diverse molecules that can synergistically interfere with complex disorders. In this study we describe the safe application of ethanolic chamomile (Matricaria recutita) flowers extract (CFE) for the treatment and prevention of type 2 diabetes and associated disorders. We show in vitro that this extract activates in particular nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) and its isotypes. In a cellular context, in human primary adipocytes CFE administration (300 µg/ml) led to specific expression of target genes of PPARγ, whereas in human hepatocytes CFE-induced we detected expression changes of genes that were regulated by PPARα. In vivo treatment of insulin-resistant high-fat diet (HFD)-fed C57BL/6 mice with CFE (200 mg/kg/d) for 6 weeks considerably reduced insulin resistance, glucose intolerance, plasma triacylglycerol, non-esterified fatty acids (NEFA) and LDL/VLDL cholesterol. Co-feeding of lean C57BL/6 mice a HFD with 200 mg/kg/d CFE for 20 weeks showed effective prevention of fatty liver formation and hepatic inflammation, indicating additionally hepatoprotective effects of the extract. Moreover, CFE treatment did not reveal side effects, which have otherwise been associated with strong synthetic PPAR-targeting molecules, such as weight gain, liver disorders, hemodilution or bone cell turnover. Taken together, modulation of PPARs and other factors by chamomile flowers extract has the potential to prevent or treat type 2 diabetes and related disorders.
authors.affiliation: Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Berlin, Germany ; Department of Biology, Chemistry, and Pharmacy, Free University of Berlin, Berlin, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Weidner
authors.forename: Sylvia J
authors.initials: SJ
authors.lastname: Wowro
authors.forename: Morten
authors.initials: M
authors.lastname: Rousseau
authors.forename: Anja
authors.initials: A
authors.lastname: Freiwald
authors.forename: Vitam
authors.initials: V
authors.lastname: Kodelja
authors.forename: Heba
authors.initials: H
authors.lastname: Abdel-Aziz
authors.forename: Olaf
authors.initials: O
authors.lastname: Kelber
authors.forename: Sascha
authors.initials: S
authors.lastname: Sauer
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D020843:Chamomile / Q000737:chemistry*; D059305:Diet, High-Fat; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D035264:Flowers / Q000737:chemistry*; D005786:Gene Expression Regulation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007333:Insulin Resistance / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D010936:Plant Extracts / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation
chemical_list: D007004:Hypoglycemic Agents; D047495:PPAR gamma; D047492:Peroxisome Proliferator-Activated Receptors; D010936:Plant Extracts