Lim Sehyun, Lim Chiyeon, Cho Suin
School of Public Health, Far East University, Eumseong, Republic of Korea.
Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, United States.
Front Pharmacol. 2024 Mar 14;15:1329895. doi: 10.3389/fphar.2024.1329895. eCollection 2024.
In traditional Asian medicine, Hort also known as "Chuanxiong", is mainly used for improving blood circulation or for analgesic and anti-inflammatory purposes, but they also have a long history of use for pain disorders in the head and face, such as headache. Despite the possibility that the plant is effective for diseases such as cerebral infarction and vascular dementia (VaD), the mechanism of action is not well understood. To determine if the dried rhizomes of (Chuanxiong Rhizoma, CR) methanol extract (CRex) has activity in a VaD mice model. Through network analysis, we confirm that CR is effective in cerebrovascular diseases. In mice, we induce cognitive impairment, similar to VaD in humans, by chronically reducing the cerebral blood flow by performing bilateral common carotid artery stenosis (BCAS) and administering CRex for 6 weeks. We measure behavioral changes due to cognitive function impairment and use immunofluorescence staining to confirm if CRex can inhibit the activation of astrocytes and microglia involved in the inflammatory response in the brain. We quantify proteins involved in the mechanism, such as mitogen-activated protein kinases (MAPK), in the hippocampus and surrounding white matter, and analyze gene expression and protein interaction networks through RNA sequencing to interpret the results of the study. CRex administration rescued cognitive impairment relating to a novel object and inhibited the activation of astrocytes and microglia. Western blotting analysis revealed that CRex regulated the changes in protein expression involved in MAPK signaling such as extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38). The administration of CRex suppressed approximately 44% of the pathological changes in gene expression caused by BCAS. CRex extract effectively inhibited cognitive impairment caused by BCAS, and the mechanism through which this occurred is inhibited activation of astrocytes and microglia.
在传统亚洲医学中，川芎也被称为“Hort”，主要用于促进血液循环或用于止痛和抗炎，但它们在治疗头部和面部疼痛疾病（如头痛）方面也有悠久的使用历史。尽管这种植物可能对脑梗死和血管性痴呆（VaD）等疾病有效，但其作用机制尚不清楚。为了确定川芎甲醇提取物（CRex）在VaD小鼠模型中是否具有活性。通过网络分析，我们证实川芎在脑血管疾病中有效。在小鼠中，我们通过双侧颈总动脉狭窄（BCAS）长期减少脑血流量来诱导类似于人类VaD的认知障碍，并给予CRex 6周。我们测量由于认知功能障碍引起的行为变化，并使用免疫荧光染色来确认CRex是否可以抑制参与大脑炎症反应的星形胶质细胞和小胶质细胞的激活。我们对海马体和周围白质中参与该机制的蛋白质（如丝裂原活化蛋白激酶（MAPK））进行定量，并通过RNA测序分析基因表达和蛋白质相互作用网络以解释研究结果。给予CRex可挽救与新物体相关的认知障碍，并抑制星形胶质细胞和小胶质细胞的激活。蛋白质印迹分析显示，CRex调节了参与MAPK信号传导的蛋白质表达变化，如细胞外信号调节激酶（ERK）和p38丝裂原活化蛋白激酶（p38）。给予CRex可抑制约44%由BCAS引起的基因表达病理变化。CRex提取物有效抑制了由BCAS引起的认知障碍，其发生机制是抑制星形胶质细胞和小胶质细胞的激活。
