Obesity is associated with skeletal muscle insulin resistance and the development of metabolic syndrome. Undifferentiated skeletal muscle cells are sensitive to oxidative stress. Berberine hydrochloride (BBR) improves insulin resistance and… Click to show full abstract
Obesity is associated with skeletal muscle insulin resistance and the development of metabolic syndrome. Undifferentiated skeletal muscle cells are sensitive to oxidative stress. Berberine hydrochloride (BBR) improves insulin resistance and exhibits anti-inflammatory properties. However, the underlying mechanism and the cell signaling pathways involved remain largely elusive. We therefore investigated the anti-inflammatory effects of BBR and the signaling pathways using skeletal C2C12 myoblast cells. Undifferentiated C2C12 myoblast cells were treated with interleukin-1β (IL-1β) alone or in combination with tumor necrosis factor-α (TNF-α) in the presence or absence of BBR. We found that BBR reduced the cytokine-induced expression of inducible nitric oxide synthase (iNOS) and stress-related kinases including, p-38 mitogen-activated protein kinase (p38 MAPK), NF-kB, and Stress-activated protein kinases /Jun amino-terminal kinases (SAPK/JNK) in C2C12 myoblast cells. Furthermore, BBR reversed cytokine-mediated suppression of AMP-activated protein kinase (AMPK-α), Sirtuin-1(SIRT-1), and PPAR-γ coactivator 1-α (PGC-1α). In addition, cytokine induced reduction of mitochondrial marker proteins and function were rescued after BBR treatment. Catalase, an antioxidant enzyme, was elevated after BBR treatment. Our results demonstrate that BBR ameliorates cytokine-induced inflammation. The anti-inflammatory effect of BBR in skeletal progenitor cells is mediated through pathways including activation of the AMPKα-SIRT-1-PGC-1 α, inhibition of the Mitogen-activated protein kinase kinase 4 (MKK4)-SAP/JUNK-C-JUN as well as protection of mitochondrial bioenergetics . BBR may be a potential medication for metabolic syndrome.
               
Click one of the above tabs to view related content.