Department of Hepatology, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China.
Department of Hepatology, Guangdong Hospital of Traditional Chinese Medicine in Zhuhai, Zhuhai, Guangdong 519015, China.
Int Immunopharmacol. 2021 Jan;90:107151. doi: 10.1016/j.intimp.2020.107151. Epub 2020 Dec 6.
The activation of hepatic stellate cells (HSCs) has been considered one of the major events in hepatic fibrosis. Amygdalin has been used to treat cancers and alleviate pain; however, its role and mechanism in HSC activation and hepatic fibrosis remain unclear. In the present study, transforming growth factor-beta 1 (TGF-β1) stimulated the activation of HSCs, as indicated by significantly increased alpha-smooth muscle actin (α-SMA), desmin, collagen I, and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein levels. Amygdalin treatment dramatically suppressed TGF-β1-induced HSC proliferation and activation. Moreover, amygdalin treatment also reduced the TGF-β1-induced secretion of cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), platelet-derived growth factor (PDGF), and chemokine (C-C motif) ligand 2 (CCL2), as well as the phosphorylation of Smad2, Smad3, and p65. In the CCl-stimulated liver fibrosis rat model, amygdalin treatment improved liver fibrosis and liver damage by reducing focal necrosis, collagen fiber accumulation, and the protein levels of α-SMA, desmin, collagen I, and TIMP-1 in hepatic tissue samples and reducing serum alanine transaminase (ALT) and aspartate transaminase (AST) levels. In conclusion, we demonstrated the suppressive effects of amygdalin in TGF-β1-induced HSC activation through modulating proliferation, fibrogenesis, and inflammation signaling in vitro and the antifibrotic effects of amygdalin in CCl-stimulated hepatic fibrosis in rats in vivo.
肝星状细胞（HSCs）的激活被认为是肝纤维化的主要事件之一。杏仁苷已被用于治疗癌症和缓解疼痛；然而，其在 HSC 激活和肝纤维化中的作用和机制尚不清楚。在本研究中，转化生长因子-β1（TGF-β1）刺激 HSCs 的激活，表现为α-平滑肌肌动蛋白（α-SMA）、结蛋白、胶原 I 和金属蛋白酶组织抑制剂-1（TIMP-1）蛋白水平显著增加。杏仁苷治疗显著抑制 TGF-β1 诱导的 HSC 增殖和激活。此外，杏仁苷治疗还降低了 TGF-β1 诱导的细胞因子分泌，包括肿瘤坏死因子-α（TNF-α）、白细胞介素 6（IL-6）、血小板衍生生长因子（PDGF）和趋化因子（C-C 基序）配体 2（CCL2），以及 Smad2、Smad3 和 p65 的磷酸化。在 CCl 刺激的肝纤维化大鼠模型中，杏仁苷治疗通过减少肝组织样本中焦点坏死、胶原纤维积累以及 α-SMA、结蛋白、胶原 I 和 TIMP-1 的蛋白水平，降低血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平，改善肝纤维化和肝损伤。总之，我们证明了杏仁苷通过调节体外 TGF-β1 诱导的 HSC 激活中的增殖、纤维化和炎症信号，以及体内 CCl 刺激的肝纤维化大鼠中的抗纤维化作用，具有抑制作用。
