Abstract

Non-alcoholic steatohepatitis (NASH) is a progressive fibrotic form of non-alcoholic fatty liver disease. Liver fibrosis leads to liver cancer and cirrhosis, and drug therapy for NASH remains lacking. Ninjin’yoeito (NYT) has shown antifibrotic effects in a model of liver fibrosis without steatosis but has not been studied for NASH. Therefore, we evaluated the efficacy of NYT in mice fed a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) as a NASH model. Compared with the normal diet group, mice fed CDAHFD showed decreased body weight and increased white adipose tissue, liver weight, and triglyceride content in the liver. Furthermore, a substantial increase in the hepatic concentration of hydroxyproline, expression of α-smooth muscle actin (α-SMA), and transforming growth factor-β was observed in CDAHFD-fed mice. Masson’s trichrome and Picro-Sirius red staining revealed a remarkable increase in collagen fiber compared with the normal diet group. Compared with mice that received CDAHFD alone, those supplemented with NYT exhibited reduced hepatic triglyceride and hydroxyproline levels and α-SMA expression. Additionally, compared with the group fed CDAHFD alone, the stained liver tissues of NYT-treated mice exhibited a reduction in Masson’s trichrome- and Picro-Sirius red-positive areas. Locomotor activity was significantly reduced in the CDAHFD-fed group compared with the normal diet group. In the NYT-treated group, the CDAHFD-induced decrease in locomotor activity was significantly suppressed. The findings indicate that NYT inhibited fatty and fibrotic changes in the livers of NASH mice and alleviated the decrease in locomotor activity. Therefore, NYT may serve as a novel therapeutic approach for NASH.

Graphical abstract

中文翻译：

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Ninjin'yoeito对非酒精性脂肪性肝炎模型小鼠肝脏脂肪变性/纤维化的保护作用

摘要

非酒精性脂肪性肝炎 (NASH) 是非酒精性脂肪肝病的一种进行性纤维化形式。肝纤维化会导致肝癌和肝硬化，而 NASH 的药物治疗仍然缺乏。Ninjin'yoeito (NYT) 在无脂肪变性的肝纤维化模型中显示出抗纤维化作用，但尚未针对 NASH 进行研究。因此，我们评估了 NYT 对饲喂缺乏胆碱、L-氨基酸限定的高脂肪饮食 (CDAHFD) 的小鼠作为 NASH 模型的功效。与正常饮食组相比，喂食CDAHFD的小鼠体重减轻，白色脂肪组织、肝脏重量和肝脏中甘油三酯含量增加。此外，在喂食 CDAHFD 的小鼠中观察到羟脯氨酸的肝脏浓度、α-平滑肌肌动蛋白 ( α-SMA ) 的表达和转化生长因子-β 的显着增加。Masson 的三色和 Picro-Sirius 红染色显示，与正常饮食组相比，胶原纤维显着增加。与单独接受 CDAHFD 的小鼠相比，补充 NYT 的小鼠表现出肝甘油三酯和羟脯氨酸水平以及α-SMA表达降低。此外，与单独喂食 CDAHFD 的组相比，NYT 处理小鼠的染色肝组织显示出 Masson 三色和 Picro-Sirius 红阳性区域的减少。与正常饮食组相比，CDAHFD 喂养组的运动活动显着降低。在 NYT 治疗组中，CDAHFD 引起的运动活动下降被显着抑制。研究结果表明，NYT 抑制了 NASH 小鼠肝脏的脂肪和纤维化变化，并缓解了运动活动的下降。因此，NYT 可能作为 NASH 的一种新的治疗方法。

图形概要