Zhao Yingchun, Liu Xinglong, Ding Chuanbo, Gu Yan, Liu Wencong
College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, China.
College of Agriculture, Jilin Agricultural University, Changchun, China.
Front Pharmacol. 2021 Nov 15;12:783886. doi: 10.3389/fphar.2021.783886. eCollection 2021.
As a natural active substance, dihydromyricetin (DHM) has been proven to have good hepatoprotective activity. However, the therapeutic effect of DHM on liver fibrosis, which has become a liver disease threatening the health of people around the world, has not been studied to date. The purpose of this study was to investigate the effect of DHM as a new nutritional supplement on thioacetamide (TAA)-induced liver fibrosis. The liver fibrosis model was established by intraperitoneal injection of TAA (200 mg/kg, every 3 days) for 8 weeks, and oral administration of DHM (20 mg/kg and 40 mg/kg, daily) after 4 weeks of TAA-induced liver fibrosis. The results showed that DHM treatment significantly inhibited the activities of alanine aminotransferase (ALT) (37.81 ± 7.62 U/L) and aspartate aminotransferase (AST) (55.18 ± 10.94 U/L) in serum of liver fibrosis mice, and increased the levels of superoxide dismutase (SOD) and glutathione (GSH) while reversed the level of malondialdehyde (MDA). In addition, histopathological examination illustrated that TAA induced the inflammatory infiltration, apoptosis and fibroatherosclerotic deposition in liver, which was further confirmed by western-blot and immunofluorescence staining. Moreover, DHM inhibited hepatocyte apoptosis by regulating the phosphorylation level of phosphatidylinositol 3-kinase (PI3K), protein kinase-B (AKT) and its downstream apoptotic protein family. Interestingly, immunofluorescence staining showed that DHM treatment significantly inhibited alpha smooth muscle actin (α-SMA), which was a marker of hepatic stellate cell activation, and regulated the expression of transforming growth factor (TGF-β1). Importantly, supplementation with DHM significantly inhibited the release of nuclear factor kappa-B (NF-κB) signaling pathway and pro-inflammatory factors in liver tissue induced by TAA, and improved liver fiber diseases, such as tumor necrosis factor alpha (TNF-α) and recombinant rat IL-1β (IL-1β). In conclusion, the evidence of this study revealed that DHM is a potential hepatoprotective and health factor, and which also provides the possibility for the treatment of liver fibrosis.
作为一种天然活性物质，二氢杨梅素（DHM）已被证明具有良好的肝脏保护活性。然而，DHM对肝纤维化的治疗效果尚未见报道，而肝纤维化已成为一种威胁全球人类健康的肝脏疾病。本研究旨在探讨DHM作为一种新型营养补充剂对硫代乙酰胺（TAA）诱导的肝纤维化的影响。通过腹腔注射TAA（200mg/kg，每3天一次）8周建立肝纤维化模型，并在TAA诱导肝纤维化4周后口服给予DHM（20mg/kg和40mg/kg，每日一次）。结果表明，DHM治疗显著抑制了肝纤维化小鼠血清中谷丙转氨酶（ALT）（37.81±7.62U/L）和谷草转氨酶（AST）（55.18±10.94U/L）的活性，并提高了超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的水平，同时逆转了丙二醛（MDA）的水平。此外，组织病理学检查表明，TAA诱导肝脏发生炎症浸润、细胞凋亡和纤维粥样硬化沉积，western印迹和免疫荧光染色进一步证实了这一点。此外，DHM通过调节磷脂酰肌醇3激酶（PI3K）、蛋白激酶B（AKT）及其下游凋亡蛋白家族的磷酸化水平来抑制肝细胞凋亡。有趣的是，免疫荧光染色显示，DHM治疗显著抑制了α平滑肌肌动蛋白（α-SMA），α-SMA是肝星状细胞激活的标志物，并调节了转化生长因子（TGF-β1）的表达。重要的是，补充DHM显著抑制了TAA诱导的肝组织中核因子κB（NF-κB）信号通路和促炎因子的释放，并改善了肝纤维疾病，如肿瘤坏死因子α（TNF-α）和重组大鼠IL-1β（IL-1β）。总之，本研究证据表明，DHM是一种潜在的肝脏保护和健康因子，也为肝纤维化的治疗提供了可能性。
