Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China.
Oxid Med Cell Longev. 2022 Dec 2;2022:6481192. doi: 10.1155/2022/6481192. eCollection 2022.
Formononetin (FN), an isoflavone compound mainly isolated from soy and red clover, had showed its anti-inflammation, antioxidative effects in some degenerative diseases and cholestasis. However, the role of FN in protecting ischemia/reperfusion- (I/R-) induced liver injury and the possible mechanism were unclear. In this study, effects of FN on liver injury were investigated in a rat hepatic I/R model; further, mitophagy-related proteins were measured by immunoblotting or immunofluorescence. The possible roles of PHB2 and PINK1 in regulating mitophagy by FN were verified using adeno-associated virus knockdown. The results showed that FN had protective effects against hepatic I/R injury through regulating PINK1/Parkin-regulated mitophagy. Further, we found that FN inhibited PARL expression and prevented PGAM5 cropped by increasing the expression of PHB2. The knockdown of PINK1 or PHB2 both abolished the protective effects of FN. Taken together, our findings indicated that the isoflavone compound FN promoted PHB2/PINK1/Parkin-mediated mitophagy pathway to protect liver from I/R-induced injury. These results provided novel insights into the potential prevention strategies of FN and its underlying mechanisms.
芒柄花素（FN）是一种主要从大豆和红三叶草中分离出来的异黄酮化合物，已显示出其在一些退行性疾病和胆汁淤积中的抗炎、抗氧化作用。然而，FN 在保护缺血/再灌注（I/R）诱导的肝损伤中的作用及其可能的机制尚不清楚。在本研究中，在大鼠肝 I/R 模型中研究了 FN 对肝损伤的影响；进一步通过免疫印迹或免疫荧光法测量了自噬相关蛋白。使用腺相关病毒敲低验证了 PHB2 和 PINK1 通过调节 FN 调节自噬的可能作用。结果表明，FN 通过调节 PINK1/Parkin 调节的自噬对肝 I/R 损伤具有保护作用。此外，我们发现 FN 通过增加 PHB2 的表达来抑制 PARL 的表达并防止 PGAM5 被截断。敲低 PINK1 或 PHB2 均消除了 FN 的保护作用。总之，我们的研究结果表明，异黄酮化合物 FN 促进了 PHB2/PINK1/Parkin 介导的自噬途径，从而保护肝脏免受 I/R 诱导的损伤。这些结果为 FN 及其潜在机制的潜在预防策略提供了新的见解。
