关键词: Hematoma absorption Intracerebral hemorrhage JAK/STAT pathway Leonurus japonicas Houtt Molecular docking Neuronal apoptosis

Mesh : Animals Molecular Docking Simulation Apoptosis / drug effects Network Pharmacology Leonurus / chemistry Neurons / drug effects metabolism Mice Male Cerebral Hemorrhage / drug therapy Neuroprotective Agents / pharmacology chemistry isolation & purification Plant Extracts / pharmacology chemistry Janus Kinase 1 / metabolism STAT1 Transcription Factor / metabolism Disease Models, Animal

来  源:   DOI:10.1016/j.jep.2024.118223

Abstract:
BACKGROUND: Leonurus japonicus Houtt. (Labiatae), commonly known as Chinese motherwort, is a herbaceous flowering plant that is native to Asia. It is widely acknowledged in traditional medicine for its diuretic, hypoglycemic, antiepileptic properties and neuroprotection. Currently, Leonurus japonicus (Leo) is included in the Pharmacopoeia of the People\'s Republic of China. Traditional Chinese Medicine (TCM) recognizes Leo for its myriad pharmacological attributes, but its efficacy against ICH-induced neuronal apoptosis is unclear.
OBJECTIVE: This study aimed to identify the potential targets and regulatory mechanisms of Leo in alleviating neuronal apoptosis after ICH.
METHODS: The study employed network pharmacology, UPLC-Q-TOF-MS technique, molecular docking, pharmacodynamic studies, western blotting, and immunofluorescence techniques to explore its potential mechanisms.
RESULTS: Leo was found to assist hematoma absorption, thus improving the neurological outlook in an ICH mouse model. Importantly, molecular docking highlighted JAK as Leo\'s potential therapeutic target in ICH scenarios. Further experimental evidence demonstrated that Leo adjusts JAK1 and STAT1 phosphorylation, curbing Bax while augmenting Bcl-2 expression.
CONCLUSIONS: Leo showcases potential in mitigating neuronal apoptosis post-ICH, predominantly via the JAK/STAT mechanism.
摘要:
背景:益母草。(唇形科),俗称中国益母草,是一种原产于亚洲的草本植物。它的利尿剂在传统医学中被广泛认可,低血糖,抗癫痫特性和神经保护。目前,益母草(Leo)被列入《中华人民共和国药典》。中医(TCM)承认狮子座的无数药理属性,但其对ICH诱导的神经元凋亡的疗效尚不清楚。
目的:本研究旨在确定Leo减轻ICH后神经元凋亡的潜在靶点和调控机制。
方法:本研究采用网络药理学,UPLC-Q-TOF-MS技术,分子对接,药效学研究,西方印迹,和免疫荧光技术探讨其潜在机制。
结果:发现Leo辅助血肿吸收,从而改善ICH小鼠模型的神经前景。重要的是,分子对接强调JAK是ICH场景中Leo的潜在治疗靶点。进一步的实验证据表明,狮子座调节JAK1和STAT1磷酸化,抑制Bax,同时增加Bcl-2表达。
结论:Leo展示了减轻ICH后神经元凋亡的潜力,主要通过JAK/STAT机制。
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