A dahlia flower extract has antidiabetic properties by improving insulin function in the brain  

作　　者：Dominik Pretz Philip M.Heyward Jeremy Krebs Joel Gruchot Charles Barter Pat Silcock Nerida Downes Mohammed Zubair Rizwan Alisa Boucsein Julia Bender Elaine J.Burgess Geke Aline Boer Pramuk Keerthisinghe Nigel B.Perry Alexander Tups 

机构地区：[1]Centre for Neuroendocrinology,School of Biomedical Sciences,University of Otago,Dunedin 9054,New Zealand [2]Department of Physiology,School of Biomedical Sciences,University of Otago,Dunedin 9054,New Zealand [3]Maurice Wilkins Centre for Molecular Biodiscovery,University of Auckland,Auckland 1010,New Zealand [4]Department of Medicine,University of Otago,Wellington,Wellington South 6242,New Zealand [5]Centre for Endocrine Diabetes and Obesity Research,Wellington Regional Hospital,Newtown,Wellington 6021,New Zealand [6]Product Development Research Centre,University of Otago,Dunedin 9054,New Zealand [7]Department of Chemistry,The New Zealand Institute for Plant and Food Research,University of Otago,Dunedin 9054,New Zealand

出　　处：《Life Metabolism》2023年第4期39-50,共12页生命（代谢（英文）

基　　金：For mice,all procedures were approved by the UoO Animal Ethics Committee.For humans,the trial(registration number U1111-1201-6917)was approved by the NZ Ministry of Health,Central Health and Disability Ethics Committee(17/CEN/194)in line with the guidelines of the Declarations of Helsinki and Tokyo.

摘　　要：Butein,a rare chalcone found in the toxic plant Toxicodendron vernicifluum,has been shown to regulate glucose homeostasis via inhibition of the nuclear factor kappa-B kinase subunit beta(IKKβ)/nuclear factor kappa B(NF-κB)pathway in the brain.Here,we investigated whether the nonpoisonous plant Dahlia pinnata could be a source of butein as a potential treatment for type 2 diabetes(T2D).In mice fed a high-fat diet(HFD)to induce glucose intolerance,an oral D.pinnata petal extract improved glucose tolerance at doses of 3.3 mg/kg body weight and 10 mg/kg body weight.Surprisingly,this effect was not mediated by butein alone but by butein combined with the closely related flavonoids,sulfuretin and/or isoliquiritigenin.Mechanistically,the extract improved systemic insulin tolerance.Inhibition of phosphatidylinositol 3-kinase to block insulin signaling in the brain abrogated the glucoregulatory effect of the orally administered extract.The extract reinstated central insulin signaling and normalized astrogliosis in the hypothalamus of HFD-fed mice.Using NF-κB reporter zebrafish to determine IKKβ/NF-κB activity,a potent anti-inflammatory action of the extract was found.A randomized controlled crossover clinical trial on participants with predia-betes or T2D confirmed the safety and efficacy of the extract in humans.In conclusion,we identified an extract from the flower petals of D.pinnata as a novel treatment option for T2D,potentially targeting the central regulation of glucose homeostasis as a root cause of the disease.

关 键 词：inflammation HYPOTHALAMUS signal transduction NEUROENDOCRINE arcuate nucleus 

分 类 号：R587.1[医药卫生—内分泌]