Department of Gerontology, Hospital of Traditional Chinese Medicine of Nanjing, 1 Jinglin Road, Nanjing, 210001, People's Republic of China.
Inflammation. 2011 Dec;34(6):659-67. doi: 10.1007/s10753-010-9276-2.
Berberine, a major isoquinoline alkaloid present in Chinese herb Rhizoma coptidis, is a potent inhibitor of inflammation and has anti-diabetic activity. This study aims to investigate effects of berberine on ameliorating insulin resistance and molecular mechanisms involved in HepG2 cells. Inflammatory responses and insulin resistance were induced by palmitate (PA) stimulation for 24 h. Treatment of berberine enhanced insulin-mediated glycogen synthesis and restored insulin inhibition of triglyceride secretion. Stimulation of PA resulted in IL-6 and TNF-α production in HepG2 cells, and antibody-neutralizing assay further confirmed that IL-6 and TNF-α were involved in the development of insulin resistance. Berberine effectively inhibited IL-6 and TNF-α production in a concentration-dependent manner, demonstrating its anti-inflammatory activity in hepatocytes. Meanwhile, PA-evoked inflammation impaired insulin signaling cascade and berberine improved insulin signaling cascade by modification of Ser/Thr phosphorylation of insulin receptor substrate-1(IRS-1) and downstream Akt (T308). Above results suggest that berberine improved insulin sensitivity in PA-stimulated hepatocytes and this regulation might relative with its anti-inflammatory activity.
小檗碱是存在于中国草药黄连根茎中的主要异喹啉生物碱，是一种有效的炎症抑制剂，具有抗糖尿病活性。本研究旨在探讨小檗碱改善 HepG2 细胞胰岛素抵抗的作用及其相关分子机制。用棕榈酸（PA）刺激 24 h 诱导炎症反应和胰岛素抵抗。小檗碱处理增强了胰岛素介导的糖原合成，并恢复了胰岛素对甘油三酯分泌的抑制作用。PA 刺激导致 HepG2 细胞中 IL-6 和 TNF-α的产生，抗体中和试验进一步证实 IL-6 和 TNF-α参与了胰岛素抵抗的发生。小檗碱呈浓度依赖性有效抑制 IL-6 和 TNF-α的产生，显示其在肝细胞中的抗炎活性。同时，PA 诱导的炎症破坏了胰岛素信号级联，而小檗碱通过改变胰岛素受体底物-1（IRS-1）和下游 Akt（T308）的 Ser/Thr 磷酸化改善了胰岛素信号级联。上述结果表明，小檗碱改善了 PA 刺激的肝细胞胰岛素敏感性，这种调节可能与其抗炎活性有关。
