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

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.

[Action of an extract of Vanda coerulea on the senescence of skin fibroblasts]. / Action d'un extrait de Vanda coerulea sur la sénescence de fibroblastes cutanés.

The family of the orchids to date is poorly studied as a potential source of molecules with biological activity. The phytochemical analysis of extracts of Vanda coerulea stems (Orchidaceae), the isolation and the purification of the secondary metabolites realized by CLHP followed with high-resolution mass spectrometry and mono and two-dimensional nuclear magnetic resonance made it possible to identify the joint presence in an orchid of three stilbenoïds i.e, imbricatin, methoxycoelonin and gigantol. By flow cytometry, it is shown that the replicative senescence of human normal skin fibroblasts involves a reduction in the number of cells in phase S. A proteins chips technology dedicated to cell cycle proteins makes it possible to correlate this decrease of the number of cells in phase S to a decrease in cyclin E and cyclin dependant kinase 2, cdk2. The treatment by an ethanolic extract of stems of Vanda coerulea titrated in the three stilbenoids restores the percentage at an equivalent rate to that of young cells and the rate of cyclin E and, cdk2, thus bringing a beginning of explanation of their mechanism. These activities let predict an interesting potential as active ingredients to fight against the visible signs of cutaneous ageing.