title: The caffeoylquinic acid-rich Pandanus tectorius fruit extract increases insulin sensitivity and regulates hepatic glucose and lipid metabolism in diabetic db/db mice.
abstract: Caffeoylquinic acids (CQAs) are widely distributed in various foods. While some CQAs have been shown to possess antihyperglycemic activities, whether it is beneficial for diabetes patients to ingest CQA-rich foods has still to be known. In this work, the antihyperglycemic and antihyperlipidemic effects of CQA-rich Pandanus tectorius fruit extract (PTF) was investigated in diabetic db/db mice. Treatment with PTF (200 mg/kg) significantly decreased body weight and fasting glucose level, alleviated hyperinsulinism and hyperlipidemia and declined glucose area under the curve in oral glucose tolerance test and insulin tolerance test. The elevated levels of serum proinflammatory cytokines and islet hypertrophy in db/db mice were remarkably attenuated by PTF treatment. Biochemical analysis showed that administration of PTF significantly stimulated the phosphorylation of AMP-activated protein kinase (AMPK) and Akt substract of 160 kDa (AS160), and enhanced the expression and translocation of glucose transporter type 4 (GLUT4) in skeletal muscles. It also increased the activity of hexokinase, decreased the expression of glucose 6-phosphatase and phosphoenolpyruvate carboxykinase and switched the transcription of several key lipid metabolic genes in the liver, which, in turn, improved hepatic glucose and lipid profiles as determined by nuclear magnetic resonance-based metabolomics. Overall, the CQA-rich PTF is beneficial for the treatment of diabetes. It may alleviate hyperglycemia and dyslipidemia via activation of AMPK-AS160-GLUT4 pathway in skeletal muscles and inhibition of gluconeogenesis and lipogenesis in the liver.
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
authors.forename: Chongming
authors.initials: C
authors.lastname: Wu
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
authors.forename: Xiaopo
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Luan
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
authors.forename: Guibo
authors.initials: G
authors.lastname: Sun
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Sun
authors.affiliation: Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
authors.forename: Xiaoliang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China. Electronic address: pguo@implad.ac.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100094, China. Electronic address: xdxu@implad.ac.cn.
authors.forename: Xudong
authors.initials: X
authors.lastname: Xu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000178:diet therapy* / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005638:Fruit / Q000737:chemistry; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D031673:Pandanaceae / Q000737:chemistry*; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011801:Quinic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C528734:GLUT4 enhancer factor, mouse; D007004:Hypoglycemic Agents; D010936:Plant Extracts; D014157:Transcription Factors; C472707:caffeoylquinic acid; D011801:Quinic Acid; D055372:AMP-Activated Protein Kinases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D005947:Glucose
keywords: AMPK; Caffeoylquinic acid; Diabetes; GLUT4; Hyperlipidemia; Pandanus tectorius fruit