The protective effects of Ninjin'yoeito against liver steatosis/fibrosis in a non-alcoholic steatohepatitis model mouse.

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-ß 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.

[Effects of Yokukansankachimpihange on Memantine-induced Dizziness in Mice with Memory Impairment].

Memantine (Mem) is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist used in the treatment of Alzheimer's disease. However, side effects, including dizziness, headache and confusion, have been reported. Therefore, although it reduces the symptoms of dementia, such as memory loss, its use is limited by side effects for patients at risk of injury. In the present study, we investigated the effects of the Japanese Kampo medicine yokukansankachimpihange (YKSCH) on Mem-induced dizziness in a mouse model of memory impairment. Mem (20 mg/kg B.W., p.o.) reduced the performance score during the beam balance test and walking time on a rotarod, confirming the disrupted sense of balance and motor coordination. In contrast, YKSCH (750 mg/kg B.W., p.o.) significantly suppressed this disruption of balance and motor coordination in mice. Moreover, YKSCH did not attenuate the ameliorative effects of Mem on learning and memory impairment in the Y-maze test or step-through passive avoidance task. Spatial learning and memory significantly recovered in the Mem-treated group and Mem plus YKSCH-treated group, suggesting no pharmacological interaction between Mem and YKSCH in mice. Therefore, YKSCH may be effective at alleviating the Mem-induced equilibrium disturbance in mice with memory impairment without reducing its memory disorder improvement effects. Our study may be useful for future studies on the combined use of Mem and YKSCH in the treatment of Alzheimer's disease.