College of life sciences, Jiangxi Normal university, Nanchang, Jiangxi, China.
College of life sciences, Jiangxi Normal university, Nanchang, Jiangxi, China; Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Ji'an, Jiangxi, China; Jiangxi Key Laboratory of Developmental Biology of Organs, Ji'an, 343009, Jiangxi, China.
Chemosphere. 2020 Oct;256:127038. doi: 10.1016/j.chemosphere.2020.127038. Epub 2020 May 11.
Baicalein is a flavonoid that is widely found in plants. Studies have shown that baicalein has anti-inflammatory, anti-cancer, and liver-protective effects. However, the effects of baicalein on TAA-induced toxicity and the underlying molecular mechanisms in zebrafish larvae are still unknown. Here, we investigated the effects of baicalein on liver development and its anti-inflammatory effects in zebrafish larvae. The results showed that baicalein has significant anti-embryonic developmental toxicity and significant antioxidant and anti-inflammatory capabilities in TAA-induced zebrafish larvae and promotes liver development and cell proliferation, reduces the expression of apoptotic proteins, and induces the expression of anti-apoptotic proteins. At the molecular level of TAA-treated zebrafish larvae, there was a decrease in the relative expression levels of mRNAs of three subfamilies, P38, ERK1, and ERK2, of the MAPK-signaling pathway and of the products of peroxisome proliferator-activated receptor (PPAR)α. Compared with TAA-treated zebrafish larvae, zebrafish larvae treated with baicalein showed an increase in the relative expression levels of P38, ERK1, and ERK2 mRNAs and the downstream products of PPARα. When MAPK signal inhibitor (SB203580) was added, it was found that liver development was inhibited and baicalin had no protective effect on TAA induced hepatotoxicity in zebrafish larvae. The results showed baicalein can protect the zebrafish larvae against toxicity induced by TAA through MAPK signal pathway. Several molecular mechanisms discovered in this study may help in the development of new drugs.
白杨素是一种广泛存在于植物中的类黄酮。研究表明，白杨素有抗炎、抗癌和保肝作用。然而，白杨素对 TAA 诱导的毒性及其在斑马鱼幼虫中的潜在分子机制的影响尚不清楚。在这里，我们研究了白杨素对肝脏发育的影响及其对斑马鱼幼虫的抗炎作用。结果表明，白杨素对 TAA 诱导的斑马鱼幼虫具有显著的抗胚胎发育毒性和显著的抗氧化和抗炎能力，促进肝脏发育和细胞增殖，降低凋亡蛋白的表达，并诱导抗凋亡蛋白的表达。在 TAA 处理的斑马鱼幼虫的分子水平上，MAPK 信号通路的 P38、ERK1 和 ERK2 三个亚家族的 mRNA 及其产物过氧化物酶体增殖物激活受体 (PPAR)α 的相对表达水平降低。与 TAA 处理的斑马鱼幼虫相比，用白杨素处理的斑马鱼幼虫 P38、ERK1 和 ERK2 mRNA 及其下游产物 PPARα 的相对表达水平增加。当加入 MAPK 信号抑制剂 (SB203580) 时，发现肝脏发育受到抑制，白杨素对 TAA 诱导的斑马鱼幼虫肝毒性没有保护作用。结果表明，白杨素可以通过 MAPK 信号通路保护斑马鱼幼虫免受 TAA 诱导的毒性。本研究发现的几种分子机制可能有助于开发新的药物。
