Bioactive compounds from Artemisia dracunculus L. activate AMPK signaling in skeletal muscle

B. Vandanmagsar, Y. Yu, C. Simmler, T. N. Dang, P. Kuhn, A. Poulev, D. M. Ribnicky, G. F. Pauli, Z. E. Floyd

Research output: Contribution to journalArticlepeer-review

Abstract

An extract from Artemisia dracunculus L. (termed PMI-5011) improves glucose homeostasis by enhancing insulin action and reducing ectopic lipid accumulation, while increasing fat oxidation in skeletal muscle tissue in obese insulin resistant male mice. A chalcone, DMC-2, in PMI-5011 is the major bioactive that enhances insulin signaling and activation of AKT. However, the mechanism by which PMI-5011 improves lipid metabolism is unknown. AMPK is the cellular energy and metabolic sensor and a key regulator of lipid metabolism in muscle. This study examined PMI-5011 activation of AMPK signaling using murine C2C12 muscle cell culture and skeletal muscle tissue. Findings show that PMI-5011 increases Thr172-phosphorylation of AMPK in muscle cells and skeletal muscle tissue, while hepatic AMPK activation by PMI-5011 was not observed. Increased AMPK activity by PMI-5011 affects downstream signaling of AMPK, resulting in inhibition of ACC and increased SIRT1 protein levels. Selective deletion of DMC-2 from PMI-5011 demonstrates that compounds other than DMC-2 in a “DMC-2 knock out extract” (KOE) are responsible for AMPK activation and its downstream effects. Compared to 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and metformin, the phytochemical mixture characterizing the KOE appears to more efficiently activate AMPK in muscle cells. KOE-mediated AMPK activation was LKB-1 independent, suggesting KOE does not activate AMPK via LKB-1 stimulation. Through AMPK activation, compounds in PMI-5011 may regulate lipid metabolism in skeletal muscle. Thus, the AMPK-activating potential of the KOE adds therapeutic value to PMI-5011 and its constituents in treating insulin resistance or type 2 diabetes.

Original languageEnglish (US)
Article number112188
JournalBiomedicine and Pharmacotherapy
Volume143
DOIs
StatePublished - Nov 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology

Keywords

  • AMPK
  • Artemisia dracunculus
  • Insulin resistance
  • LKB1
  • Skeletal muscle

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