School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
Traditional Chinese Medicine Department of No. 458 Hospital of PLA, Guangdong 510602, China.
J Pharmacol Sci. 2018 Mar;136(3):133-141. doi: 10.1016/j.jphs.2018.01.003. Epub 2018 Feb 2.
Oligo-peptide I-C-F-6 is a Carapax trionycis extract component that has an effect on hepatic fibrosis, however, its mechanism of action is still unclear. This study investigated whether oligo-peptide I-C-F-6 could inhibit liver fibrosis by suppressing NF-κB and Wnt/β-catenin signaling, which are important in liver fibrosis. HSC-T6 cells were treated with oligo-peptide I-C-F-6, and rats were divided randomly into five groups: control (saline), CCl, CCl plus oligo-peptide I-C-F-6 (0.12 and 0.24 mg/kg), and CCl plus colchicine (0.11 mg/kg). Here, we demonstrated that oligo-peptide I-C-F-6 ameliorated liver injury, inflammation, and hepatic fibrogenesis induced by CCl. Oligo-peptide I-C-F-6 also inhibited the activation of hepatic stellate cells (HSCs) in vivo and in vitro, as evaluated by the expression of transforming growth factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA), which is a specific marker of HSC activation. Moreover, oligo-peptide I-C-F-6 significantly reduced the expression and distribution of β-catenin, P-AKT, phospho (P)-GSK-3β, nuclear factor κB (NF-κB) P65, phospho-P65, and IκB kinase α/β (IKK-α/β) levels; additionally, IκB-α level was elevated both in vivo and in vitro. Together, these results indicate that oligo-peptide I-C-F-6 has hepatoprotective and anti-fibrotic effects in animal models of liver fibrosis, the mechanism of which may be related to modulating NF-κB and Wnt/β-catenin signaling.
寡肽 I-C-F-6 是一种龟板提取物成分，对肝纤维化有影响，但作用机制尚不清楚。本研究探讨了寡肽 I-C-F-6 是否通过抑制 NF-κB 和 Wnt/β-catenin 信号通路来抑制肝纤维化，这两个信号通路在肝纤维化中非常重要。用寡肽 I-C-F-6 处理 HSC-T6 细胞，将大鼠随机分为五组：对照组（生理盐水）、CCl4 组、CCl4 加寡肽 I-C-F-6（0.12 和 0.24 mg/kg）组和 CCl4 加秋水仙碱（0.11 mg/kg）组。结果表明，寡肽 I-C-F-6 可改善 CCl4 诱导的肝损伤、炎症和肝纤维化。寡肽 I-C-F-6 还抑制了体内和体外肝星状细胞（HSCs）的活化，通过转化生长因子-β1（TGF-β1）和α-平滑肌肌动蛋白（α-SMA）的表达来评估，这是 HSCs 活化的特异性标志物。此外，寡肽 I-C-F-6 显著降低了β-catenin、P-AKT、磷酸化（P）-GSK-3β、核因子κB（NF-κB）P65、磷酸化 P65 和 IKK-α/β（IKK-α/β）的表达和分布；此外，IκB-α 水平在体内和体外均升高。综上所述，这些结果表明，寡肽 I-C-F-6 对肝纤维化动物模型具有保肝和抗纤维化作用，其机制可能与调节 NF-κB 和 Wnt/β-catenin 信号通路有关。
