Chlorogenic acid (CGA) is a phenylpropanoid compound that is well known to improve the antioxidant capacity and other biological activities. However, the roles of CGA in the liver development of organisms are unclear. In the present study, we aimed to investigate the function of CGA in the hepatic development in thioacetamide (TAA)-induced zebrafish embryos. We found that CGA exerted certain beneficial effects on zebrafish larvae from TAA-exposed zebrafish embryos, such as increasing the liver size, body length, heart rate, acetylcholinesterase activity, and motor ability. In addition, CGA displayed an antioxidant effect on TAA-induced zebrafish embryos by enhancing the activities of superoxide dismutase (SOD), catalase (CAT), and glucose-6-phosphate dehydrogenase (G6PDH), and decreasing of the contents of malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO). The results of western blotting analysis showed that CGA inhibited cell apoptosis by increasing the levels of Bcl2 apoptosis regulator and decreasing the levels of Bcl2 associated X (Bax), apoptosis regulator and tumor protein P53. Moreover, CGA promoted cell proliferation in TAA-induced zebrafish larvae, as detected using proliferating cell nuclear antigen fluorescence immunostaining. In addition, CGA inhibited the expression of Wnt signaling pathway genes Dkk1 (encoding Dickkopf Wnt signaling pathway inhibitors), and promoted the expression of Lef1 (encoding lymphoid enhancer binding factor 1) and Wnt2bb (encoding wingless-type MMTV integration site family, member 2Bb). When the Wnt signal inhibitor IWR-1 was added, there was no significant change in liver development in the IWR-1 + TAA group compared with the IWR-1 + TAA + CGA group (p <0.05), which suggested that CGA regulates liver development via Wnt signaling pathway. Overall, our results suggested that CGA might alleviate TAA-induced toxicity in zebrafish and promote liver development through the Wnt signaling pathway, which provides a basis for the therapeutic effect of CGA on liver dysplasia.

绿原酸 (CGA) 是一种苯丙烷类化合物，众所周知，它可以提高抗氧化能力和其他生物活性。然而，CGA 在生物体肝脏发育中的作用尚不清楚。在本研究中，我们旨在研究 CGA 在硫代乙酰胺 (TAA) 诱导的斑马鱼胚胎肝脏发育中的作用。我们发现 CGA 对暴露于 TAA 的斑马鱼胚胎中的斑马鱼幼虫具有某些有益作用，例如增加肝脏大小、体长、心率、乙酰胆碱酯酶活性和运动能力。此外，CGA 通过增强超氧化物歧化酶 (SOD)、过氧化氢酶 (CAT) 和葡萄糖-6-磷酸脱氢酶 (G6PDH) 的活性，降低丙二醛 (MDA) 的含量，对 TAA 诱导的斑马鱼胚胎具有抗氧化作用。 ), 活性氧（ROS）和一氧化氮（NO）。免疫印迹分析结果显示，CGA通过增加Bcl2凋亡调节因子的水平和降低Bcl2相关X（Bax）、凋亡调节因子和肿瘤蛋白P53的水平来抑制细胞凋亡。此外，如使用增殖细胞核抗原荧光免疫染色检测到的，CGA 促进了 TAA 诱导的斑马鱼幼虫的细胞增殖。此外，CGA抑制Wnt信号通路基因Dkk1（编码Dickkopf Wnt信号通路抑制剂）的表达，促进Lef1（编码淋巴增强子结合因子1）和Wnt2bb（编码无翼型MMTV整合位点家族，成员2Bb）的表达）。当加入 Wnt 信号抑制剂 IWR-1 时，与IWR-1 + TAA + CGA组相比，IWR-1 + TAA组肝脏发育无明显变化（p <0.05），提示CGA通过Wnt信号通路调节肝脏发育。总体而言，我们的研究结果表明，CGA 可能通过 Wnt 信号通路减轻 TAA 诱导的斑马鱼毒性并促进肝脏发育，这为 CGA 对肝发育不良的治疗作用提供了基础。