a Physician Assistant Program, College of Health Professions, Central Michigan University, Mount Pleasant, MI 48859, USA.
b College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USA.
Can J Physiol Pharmacol. 2019 Aug;97(8):699-707. doi: 10.1139/cjpp-2018-0653. Epub 2019 Apr 26.
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 alone or in combination with tumor necrosis factor-α in the presence or absence of BBR. We found that BBR reduced the cytokine-induced expression of inducible nitric oxide synthase and stress-related kinases including p-38 mitogen-activated protein kinase, nuclear factor kappa B (NF-κB), 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 (AMPKα), sirtuin-1 (SIRT-1), and PPAR-γ coactivator-1α (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-1α, inhibition of the mitogen-activated protein kinase 4 (MKK4)-SAPK/JNK-C-JUN, as well as protection of mitochondrial bioenergetics. BBR may be a potential medication for metabolic syndrome.
肥胖与骨骼肌胰岛素抵抗和代谢综合征的发生有关。未分化的骨骼肌细胞对氧化应激敏感。盐酸小檗碱（BBR）可改善胰岛素抵抗，并具有抗炎作用。然而，其潜在的机制和涉及的细胞信号通路在很大程度上仍不清楚。因此，我们使用骨骼肌 C2C12 成肌细胞研究了 BBR 的抗炎作用及其信号通路。未分化的 C2C12 成肌细胞用白细胞介素-1β单独或与肿瘤坏死因子-α联合处理，同时存在或不存在 BBR。我们发现 BBR 降低了细胞因子诱导的诱导型一氧化氮合酶和应激相关激酶（包括 p-38 丝裂原活化蛋白激酶、核因子 kappa B（NF-κB）和应激激活蛋白激酶/Jun 氨基末端激酶（SAPK/JNK））在 C2C12 成肌细胞中的表达。此外，BBR 逆转了细胞因子介导的 AMP 激活蛋白激酶（AMPKα）、沉默调节蛋白-1（SIRT-1）和过氧化物酶体增殖物激活受体-γ共激活因子-1α（PGC-1α）的抑制。此外，BBR 处理后，细胞因子诱导的线粒体标记蛋白和功能的减少得到了恢复。抗氧化酶过氧化氢酶在 BBR 处理后升高。我们的结果表明，BBR 可改善细胞因子诱导的炎症。BBR 在骨骼肌祖细胞中的抗炎作用是通过激活 AMPKα-SIRT-1-PGC-1α、抑制丝裂原活化蛋白激酶 4（MKK4）-SAPK/JNK-C-JUN 以及保护线粒体生物能学等途径介导的。BBR 可能是治疗代谢综合征的潜在药物。
