Rosmarinic Acid, a Rosemary Extract Polyphenol, Increases Skeletal Muscle Cell Glucose Uptake and Activates AMPK

Abstract

Skeletal muscle is a major insulin-target tissue and plays an important role in glucose homeostasis. Impaired insulin action in muscles leads to insulin resistance and type 2 diabetes mellitus. 5′ AMP-activated kinase (AMPK) is an energy sensor, its activation increases glucose uptake in skeletal muscle and AMPK activators have been viewed as a targeted approach in combating insulin resistance. We previously reported AMPK activation and increased muscle glucose uptake by rosemary extract (RE). In the present study, we examined the effects and the mechanism of action of rosmarinic acid (RA), a major RE constituent, in L6 rat muscle cells. RA (5.0 µM) increased glucose uptake (186 ± 4.17% of control, p < 0.001) to levels comparable to maximum insulin (204 ± 10.73% of control, p < 0.001) and metformin (202 ± 14.37% of control, p < 0.001). Akt phosphorylation was not affected by RA, while AMPK phosphorylation was increased. The RA-stimulated glucose uptake was inhibited by the AMPK inhibitor compound C and was not affected by wortmannin, an inhibitor of phosphoinositide 3-kinase (PI3K). The current study shows an effect of RA to increase muscle glucose uptake and AMPK phosphorylation. RA deserves further study as it shows potential to be used as an agent to regulate glucose homeostasis.

Antiobesity Effects of Purple Perilla (Perilla frutescens var. acuta) on Adipocyte Differentiation and Mice Fed a High‐fat Diet

“…Besides PPARγ , AMPK is also known to regulate lipolytic enzymes in adipose tissue . Even though the effect of PE on AMPK was not evaluated in our study, previous reports have suggested that rosmarinic acid activates AMPK pathway in different tissues to exert it beneficial effects (Abe, Saito, & Nogata, 2016;Han, Kee, & Hong, 2018;Jayanthy, Roshana Devi, Ilango, & Subramanian, 2017;Vlavcheski, Naimi, Murphy, Hudlicky, & Tsiani, 2017). Therefore, we presume that the increased mRNA expression of ATGL and HSL, despite of the reduced PPARγ expression will be due to the activation of AMPK pathway.…”

Carnosol Increases Skeletal Muscle Cell Glucose Uptake via AMPK-Dependent GLUT4 Glucose Transporter Translocation

“…Carnosol is a phenolic terpene (diterpene) found in rosemary and reported to have anti-inflammatory, antioxidant, and anticancer effects [ 17 , 18 , 19 , 20 ]. More recently, antihyperglycemic and anti-diabetic effects of rosemary and rosemary polyphenols have been reported [ 21 , 22 , 23 , 24 ].…”

Attenuation of allergen-mediated mast cell activation by rosemary extract (Rosmarinus officinalis L.)

“…We further measured the production and release of these pro‐inflammatory mediators by using the equivalent concentrations of the three main polyphenolic constituents of RE. The abundance of each of the polyphenols was measured using HPLC previously in our laboratory 52,53 and the resulting concentrations were then calculated. HPLC analysis revealed that our RE was composed of 13.39% RA, and 2.12% CA that are in line with similar values previously reported by others, 52,53 however CO was not measured.…”