The hepatoprotective effects of Salvia plebeia R. Br. extract in zebrafish (Danio rerio)
The hepatoprotective effects of Salvia plebeia R. Br. extract in zebrafish (Danio rerio)
复制标题
鼠尾草的保肝作用。
DOI：
10.1016/j.fsi.2019.10.040
复制
发表时间：
2019
影响因子：
4.7
通讯作者：
Lu Huiqiang
中科院分区：
文献类型：
--
作者：
Xiong Guanghua;Deng Yunyun;Cao Zigang;Liao Xinjun;Zhang Jun'e;Lu Huiqiang
鼠尾草。Br.是一种中草药，广泛用于治疗肝炎等多种炎症性疾病。然而，其保肝作用的分子机制尚不清楚。大多数人都不知道。在这里，我们研究了乙醇提取物的抗氧化活性和抗炎作用。斑马鱼模型中的Plebeia(SPEE)。首先，我们测定了SPEE的化学成分，并通过GC-MS分析鉴定了三种主要成分。SPEE对脂多糖诱导的斑马鱼胚胎具有明显的抗氧化作用，对ROS、CAT和SOD的活性有明显的抑制作用，且呈剂量依赖关系。其次，在硫代乙酰胺(TAA)诱导的成年斑马鱼肝细胞损伤中，SPEE显著减少脂肪空泡(HE染色)、脂肪堆积(Oil O染色)和肝细胞纤维化(Gemori染色)。同时，SPEE暴露后大鼠脑组织NO含量和脂代谢相关基因表达显著下调。第三，我们利用RNA-Seq分析来寻找成年斑马鱼肝脏中SPEE暴露后的差异表达基因(DEG)。结果表明，在TAA+、SPEE和TAA组之间共鉴定出1289个DEG，其中558个上调，731个下调。KEGG途径和GO功能分析表明，类固醇的生物合成、氧化还原和天然免疫显著丰富。从机制上讲，SPEE能显著减少TAA诱导的斑马鱼肝细胞的凋亡，促进Nrf2蛋白从胞核向胞浆的移位。此外，SPEE在对照和H_2O_2刺激条件下都能调节多种炎症细胞因子和免疫基因。促炎症细胞因子IL-1、β和肿瘤坏死因子-α在治疗后明显上调，而抗炎细胞因子如转化生长因子-β在治疗后明显下调。此外，TLR信号通路中的一些关键基因也在过氧化氢刺激的条件下被激活。综上所述，我们的结果表明SPEE在不久的将来在斑马鱼的抗氧化和抗炎作用中发挥重要作用。本研究中确定的一些成分可能是治疗炎症性疾病的新的保肝化合物的潜在来源。
Salvia plebeiaR. Br. is a traditional Chinese medicinal herb that has been widely used for the treatment of many inflammatory diseases such as hepatitis. However, the underlying molecular mechanism about the hepatoprotective effects ofS. plebeiaremains largely unknown. Here, we investigated the antioxidant activities and anti-inflammatory effects of ethanol extracts ofS. plebeia(SPEE) in the zebrafish model. Firstly, we determined the chemical compositions of SPEE and identified three major constituents by using GC-MS analysis. After that, SPEE exhibited significantly antioxidant properties in the LPS-induced zebrafish embryos, and the enzyme activities of ROS, CAT and SOD were obviously inhibited in a dose-dependent manner. Secondly, SPEE greatly reduced fat vacuoles (HE staining), lipid accumulation (Oil O staining) and hepatocyte fibrosis (Gemori staining) in the thioacetamide (TAA)-induced hepatocyte injury of adult zebrafish. Meanwhile, the NO contents and lipid metabolism-related genes were substantially down-regulated after SPEE exposure. Thirdly, we used RNA-Seq analysis to identify the differentially expressed genes (DEGs) after SPEE exposure in adult zebrafish liver. The results showed that 1289 DEGs including 558 up-regulated and 731 down-regulated were identified between the TAA + SPEE and TAA groups. KEGG pathway and GO functional analysis revealed that steroid biosynthesis, oxidation-reduction and innate immunity were significantly enriched. Mechanistically, SPEE can considerably reduce the cell apoptosis of hepatocytes and promote the translocation of Nrf2 protein from the nucleus to the cytoplasm in TAA-induced zebrafish. Moreover, SPEE can modulate various inflammatory cytokines and immune genes both in the control and H2O2-stimulated conditions. The pro-inflammatory cytokines such as IL-1β and TNF-α was markedly up-regulated but the anti-inflammatory cytokines such as TGF-β was greatly down-regulated after SPEE treatment. In addition, some key genes in the TLR signaling were also activated in the H2O2-stimulated conditions. In summary, our results suggested that SPEE had an important role in the antioxidant and anti-inflammatory effects in zebrafish in the near future. Some of the components identified in this study may be served as potential sources of new hepatoprotective compounds for the treatment of inflammatory diseases.