Abstract

Osthole is an agent isolated from Cnidium monnieri (L.) Cusson and Angelica pubescens and has been used to treat several diseases, including metabolic syndromes. To investigate the hypoglycemic effects of osthole in diabetic db/db mice and the underlying mechanisms of these effects by in vitro assay, diabetic db/db mice and cell experiments were utilized to understand its possible effects. Osthole significantly activated both PPARα and PPARγ in a dose-dependent manner based on the results of the transition transfection assay. The activation of PPARα and PPARγ by osthole also resulted in an increase in the expression of PPAR target genes such as PPAR itself, adipose fatty acid-binding protein 2, acyl-CoA synthetases, and carnitine palmitoyltransferase-1A. In vitro results suggested that osthole might be a dual PPARα/γ activator, but its chemical structure differed from that of the thiazolidinedione class of antidiabetic drugs. In addition, osthole markedly activated the AMP-activated protein kinase and its downstream acetyl CoA carboxylase molecules by increasing their phosphorylation levels. Finally, obese diabetic db/db mice were treated with osthole by different administered routes, and osthole was found to markedly reduce blood glucose level. Interestingly, osthole did not reduce the blood insulin or lipid levels, two phenomena that did occur in animals treated with insulin sensitizers like PPAR agonists. These results suggest that osthole can alleviate hyperglycemia and could be potentially developed into a novel drug for treatment of diabetes mellitus.

Original languageEnglish
Pages (from-to)309-315
Number of pages7
JournalChemico-Biological Interactions
Volume181
Issue number3
DOIs
Publication statusPublished - Oct 30 2009

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Hypoglycemic Agents
Peroxisome Proliferator-Activated Receptors
Hyperglycemia
Cnidium
Assays
Angelica
osthol
Coenzyme A Ligases
Insulin
Carnitine O-Palmitoyltransferase
Acetyl-CoA Carboxylase
Fatty Acid-Binding Proteins
Phosphorylation
AMP-Activated Protein Kinases
Metabolic Diseases
Medical problems
Transfection
Blood Glucose
Diabetes Mellitus
Animals

Keywords

  • AMPK
  • Diabetic db/db mice
  • Glucose
  • Osthole
  • Peroxisome proliferator-activated receptor

ASJC Scopus subject areas

  • Toxicology

Cite this

Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice. / Liang, Hong Jen; Suk, Fat Moon; Wang, Chung Kwe; Hung, Ling Fang; Liu, Der Zen; Chen, Nai Qi; Chen, Yu Chien; Chang, Chun Chao; Liang, Yu Chih.

In: Chemico-Biological Interactions, Vol. 181, No. 3, 30.10.2009, p. 309-315.

Research output: Contribution to journalArticle

Liang, Hong Jen ; Suk, Fat Moon ; Wang, Chung Kwe ; Hung, Ling Fang ; Liu, Der Zen ; Chen, Nai Qi ; Chen, Yu Chien ; Chang, Chun Chao ; Liang, Yu Chih. / Osthole, a potential antidiabetic agent, alleviates hyperglycemia in db/db mice. In: Chemico-Biological Interactions. 2009 ; Vol. 181, No. 3. pp. 309-315.
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AU - Chen, Nai Qi

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AU - Liang, Yu Chih

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