Department of Health Laboratory Technology, School of Public Health, China Medical University, Shenyang, Liaoning, China, 110122.
The First Affiliated Hospital of China Medical University, Shenyang, 110001, PR China.
Phytomedicine. 2024 Dec;135:156216. doi: 10.1016/j.phymed.2024.156216. Epub 2024 Nov 8.
Evidence indicates a close association between iron overload (IO) and the pathogenesis of chronic liver diseases, highlighting the potential for interventions targeted at IO to impede or decelerate the progression of chronic liver diseases. Diammonium glycyrrhizinate (DG), the medicinal form of glycyrrhizic acid, a principal constituent of licorice, has been clinically employed as a hepatoprotective agent; however, its protective effect against IO-induced liver injury and underlying molecular mechanisms remain elusive.
The aim of the present study is to investigate the hepatoprotective effect of DG against IO-induced liver injury with a focus on the gut-liver axis.
Animal models of IO-induced liver injury and DG treatment have been established in vivo. Iron deposition, liver injury, intestinal barrier damage, and liver inflammation were assessed in mice treated with iron dextran or DG. The microbiome composition in feces was analyzed using 16S rRNA full-length sequencing. Bile acids (BAs) profiles in feces were detected by UPLC-Q-TOF-MS technique, and the expression levels of receptors, enzymes or transporters involved in BAs metabolism were also determined.
DG partially reduced the iron deposition and the levels of ferrous ion in the livers of mice with IO, thereby mitigating oxidative damage. DG also improved gut microbiota dysbiosis, repaired intestinal barrier damage, inhibited endotoxin translocation to the liver, and subsequently suppressed TLR4/NF-κB/NLRP3 pathway-mediated liver inflammation caused by IO. Moreover, DG modulated BAs metabolism disorder in IO mice, reducing the accumulation of BAs in the liver.
DG alleviates IO-induced liver injury in mice by regulating the gut-liver axis. This study provides novel insights into the underlying mechanisms through which DG ameliorates liver injury caused by IO.
有证据表明，铁过载（IO）与慢性肝病的发病机制密切相关，这凸显了针对 IO 的干预措施有可能阻止或减缓慢性肝病的进展。二铵甘草酸（DG）是甘草酸的药用形式，是甘草的主要成分之一，临床上已用作保肝剂；然而，其对 IO 诱导的肝损伤的保护作用及其潜在的分子机制仍不清楚。
本研究旨在探讨 DG 对 IO 诱导的肝损伤的保护作用，重点关注肠-肝轴。
在体内建立了 IO 诱导的肝损伤动物模型和 DG 治疗模型。用右旋糖酐铁或 DG 处理小鼠，评估铁沉积、肝损伤、肠道屏障损伤和肝炎症。采用 16S rRNA 全长测序分析粪便微生物群落组成。采用 UPLC-Q-TOF-MS 技术检测粪便中胆汁酸（BAs）谱，同时测定 BAs 代谢相关受体、酶或转运体的表达水平。
DG 部分减少了 IO 小鼠肝脏中的铁沉积和亚铁离子水平，从而减轻了氧化损伤。DG 还改善了肠道微生物群失调，修复了肠道屏障损伤，抑制了内毒素向肝脏的易位，并随后抑制了 IO 引起的 TLR4/NF-κB/NLRP3 通路介导的肝炎症。此外，DG 调节了 IO 小鼠的 BAs 代谢紊乱，减少了 BAs 在肝脏中的积累。
DG 通过调节肠-肝轴缓解 IO 诱导的小鼠肝损伤。本研究为 DG 改善 IO 引起的肝损伤的潜在机制提供了新的见解。
