Licorice is a popular medicinal plant, and it has been used to treat various diseases, including liver diseases. Glycycoumarin (GCM) is a major coumarin compound isolated from licorice with favorable bioavailability property. Our previous studies have shown that GCM is capable of inhibiting lipoapoptosis in both cell culture and methionine-choline-defcient (MCD) diet-induced mouse model of non-alcoholic steatohepatitis (NASH) through mechanisms involving suppression of endoplasmic reticulum (ER) stress. Perilipin 5 (PLIN5), a newly identified lipid drop protein in the perilipin family, is highly expressed in oxidative tissues including the liver and is suggested to play an important role in protecting against hepatic lipotoxicity. Give the hepatoprotective role of PLIN5, we hypothesized that induction of PLIN5 might contribute to the hepatoprotective effect of GCM via mitigating ER stress and inflammatory responses. Results showed that PLIN5 and its downstream target Sirt1 were induced by GCM both in vitro and in vivo. Inhibition of either PLIN5 or Sirt1 led to significantly attenuated protective effect of GCM on palmitic acid (PA)-induced lipoapoptosis and inflammatory responses, supporting involvement of PLIN5-Sirt1 axis in the protective effect of GCM on hepatic lipotoxicity. The findings of the present study provide novel insight into the understanding of mechanisms underlying the hepatoprotective effect of GCM.

中文翻译：

---

PLIN5-Sirt1轴的激活参与了香豆素对肝脂质毒性的保护作用。

欧亚甘草是一种流行的药用植物，已被用于治疗各种疾病，包括肝脏疾病。甘氨酸香豆素（GCM）是从甘草中分离出来的一种主要香豆素化合物，具有良好的生物利用度。我们以前的研究表明，GCM能够通过抑制内质网（ER）应激的机制来抑制细胞培养和蛋氨酸-胆碱缺陷（MCD）饮食诱导的非酒精性脂肪性肝炎（NASH）小鼠模型中的脂质凋亡。Perilipin 5（PLIN5）是perilipin家族中一个新发现的脂质下降蛋白，在包括肝脏在内的氧化性组织中高度表达，并被认为在预防肝脂毒性中起重要作用。赋予PLIN5保肝作用，我们假设PLIN5的诱导可能通过减轻ER应激和炎症反应来促进GCM的保肝作用。结果表明，PLIN5及其下游靶标Sirt1在体外和体内均被GCM诱导。PLIN5或Sirt1的抑制导致GCM对棕榈酸（PA）诱导的脂质凋亡和炎症反应的保护作用显着减弱，从而支持PLIN5-Sirt1轴参与GCM对肝脂质毒性的保护作用。本研究的发现为理解GCM的肝保护作用机理提供了新颖的见解。PLIN5或Sirt1的抑制导致GCM对棕榈酸（PA）诱导的脂质凋亡和炎症反应的保护作用显着减弱，从而支持PLIN5-Sirt1轴参与GCM对肝脂质毒性的保护作用。本研究的发现为理解GCM的肝保护作用机制提供了新颖的见解。PLIN5或Sirt1的抑制导致GCM对棕榈酸（PA）诱导的脂质凋亡和炎症反应的保护作用显着减弱，从而支持PLIN5-Sirt1轴参与GCM对肝脂质毒性的保护作用。本研究的发现为理解GCM的肝保护作用机制提供了新颖的见解。