Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Department of Physiology, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Eur J Pharmacol. 2024 Oct 15;981:176916. doi: 10.1016/j.ejphar.2024.176916. Epub 2024 Aug 18.
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that can occur in people with acute or chronic liver disease. Here, we investigated the effects of menthol, a natural monoterpene, on HE induced by thioacetamide (TA) in male Wistar rats. The rats received 200 mg/kg of TA twice a week for four weeks and were administered 10 mg/kg of menthol intraperitoneally daily for the same period. The results showed that menthol treatment reduced oxidative stress and inflammation in the livers and hippocampi of the rats that received TA. It also lowered the levels of ammonium and liver enzymes AST, ALT, ALP, and GGT in the serum of these animals and prevented liver histopathological damage. In addition, the expression and activity of acetylcholinesterase in the hippocampus of HE model rats were decreased by menthol. Likewise, this monoterpene reduced the expression of TLR4, MyD88, and NF-κB in the hippocampus while increasing the expression of BDNF and α7-nACh receptor. Menthol also reduced neuronal death in the hippocampal cornu ammonis-1 and dentate gyrus regions and reduced astrocyte swelling, which led to improved learning and spatial memory in rats with HE. In conclusion, the study suggests that menthol may have strong protective effects on the liver and brain, making it a potential treatment for HE and neurodegenerative diseases.
肝性脑病（HE）是一种神经精神综合征，可发生在急性或慢性肝病患者中。在这里，我们研究了薄荷醇（一种天然单萜）对硫代乙酰胺（TA）诱导的雄性 Wistar 大鼠 HE 的影响。大鼠每周接受两次 200mg/kg TA，同期每天腹腔内给予 10mg/kg 薄荷醇。结果表明，薄荷醇治疗可降低 TA 处理大鼠肝脏和海马中的氧化应激和炎症。它还降低了这些动物血清中氨、肝酶 AST、ALT、ALP 和 GGT 的水平，并防止了肝组织病理学损伤。此外，薄荷醇降低了 HE 模型大鼠海马中乙酰胆碱酯酶的表达和活性。同样，这种单萜还降低了海马中 TLR4、MyD88 和 NF-κB 的表达，同时增加了脑源性神经营养因子（BDNF）和α7-nACh 受体的表达。薄荷醇还减少了海马角回和齿状回区域的神经元死亡，并减轻了星形胶质细胞肿胀，从而改善了 HE 大鼠的学习和空间记忆。总之，该研究表明薄荷醇可能对肝脏和大脑具有很强的保护作用，使其成为治疗 HE 和神经退行性疾病的潜在药物。
