Abstract

Simple SummaryAlzheimer’s disease and coronary heart disease are two ever-increasing major health concerns worldwide. Scientific studies revealed a link between Alzheimer’s disease and atherosclerosis, a major causality of coronary heart disease. Herbal medicine has been widely prescribed to treat Alzheimer’s disease and atherosclerosis. In the current study, we explored the possible therapeutic effect of Tongqiaohuoxue, a herbal medicine developed during the Qing dynasty of China for the prevention and treatment of cardiovascular disease, on Alzheimer’s disease and atherosclerosis. We discovered Tongqiaohuoxue showed therapeutic effects not only on atherosclerosis but also on Alzheimer’s disease. Tongqiaohuoxue treatment into the animal model of Alzheimer’s disease and atherosclerosis attenuated atherosclerotic plaque and brain amyloid formations, abnormalities that are characteristic of coronary heart disease and Alzheimer’s disease, respectively. Based on these findings, Tongqiaohuxue showed promising therapeutic effects for the treatment of patients with both Alzheimer’s disease and coronary heart disease.Atherosclerosis is closely associated with Alzheimer’s disease (AD). Tongqiaohuoxue decoction (THD) is a classical herbal prescription in traditional Chinese medicine widely used for the prevention and treatment of cerebrovascular disease. This study aimed to explore the therapeutic effects of THD on atherosclerosis and AD. Eight-week-old C57BL6/J wild-type and ApoE-deficient (ApoE-/-) mice were fed a high-fat and high-cholesterol diet for eight weeks, followed by oral phosphate-buffered saline vehicle or THD treatment for eight weeks further. In ApoE-/- mice, THD attenuated lipid deposition in the aorta and the brain, and abrogated atherosclerotic changes without affecting serum lipid profiles while decreasing amyloid plaque formation. In vitro assays undertaken to understand THD’s effects on lipid clearance in the aorta and brain vessels revealed that THD treatment inhibited the lipid uptake, stimulated by oxidized low-density lipoprotein, resulted in decreased endothelial cell activation through reduction in intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and monocyte chemoattractant protein-1 levels. Serum analysis revealed inhibitory effects of THD on resistin production, which has important roles in the development of both atherosclerosis and AD. In conclusion, the current study demonstrates beneficial effects of THD on the development and progression of atherosclerosis, and a possible protective role against AD.

Highlights

  • Increasing evidence suggests a link between Alzheimer’s disease (AD), vascular risk factors, and atherosclerosis in elderly patients [1]

  • Given the pathophysiological role of apoprotein E (ApoE) in atherosclerosis and AD, we investigated the blood–cerebrospinal fluid (CSF) barrier of the choroid plexus (ChP) region in ApoE-/- mice to determine the neuroprotective effects of Tongqiaohuoxue decoction (THD)

  • We uncovered the evidence of novel anti-inflammatory functions of THD in the development and progression of AD and atherosclerosis

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Summary

Introduction

Increasing evidence suggests a link between Alzheimer’s disease (AD), vascular risk factors, and atherosclerosis in elderly patients [1]. Apoprotein E (ApoE) is a polymorphic protein whose primary functions are to transport lipids and to participate in lipoprotein and cholesterol metabolism; it has been reported as a risk factor for both atherosclerosis and AD [5]. Tongqiaohuoxue decoction (THD; known as Tonggyuhwalhyeol-tang in Korea) was developed during the Qing dynasty of China (A.D. 1830). It is widely used in traditional East Asian medicine, in China, Japan, and Korea, for the prevention and treatment of cerebrovascular disease [9]

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