Abstract
Presently, the treatment options for ischemic stroke (IS) are limited due to the complicated pathological process of the disease. Chuanxiong Rhizome (CR), also known as Conioselinum anthriscoides “Chuanxiong” (rhizome), is the most widely used traditional Chinese medicine for treating stroke. This study aimed to uncover the key phytochemicals and biological functions of CR against IS through a network pharmacology approach combining with IS pathophysiology analysis. We employed permanent unilateral common carotid artery ligation to construct a mouse model of global cerebral ischemia and found that cerebral ischemia injuries were improved after 7 days of gavage treatment of CR (1,300 mg/kg/day). CR exerts protective effects on neurons mainly by acting on targets related to synaptic structure, synaptic function, neuronal survival and neuronal growth. A total of 18 phytochemicals from CR based on UHPLC-MS/MS that corresponded to 85 anti-IS targets. Coniferyl ferulate, neocnidilide and ferulic acid were identified as the key phytochemicals of CR against IS. Its brain protective effects involve anti-inflammatory, anti-oxidative stress, and anti-cell death activities and improves blood circulation. Additionally, the two most important synergistic effects of CR phytochemicals in treating IS are prevention of infection and regulation of blood pressure. In brain samples of Sham mice, L-tryptophan and vanillin were detected, while L-tryptophan, gallic acid, vanillin and cryptochlorogenic acid were detected in IS mice by UHPLC–MS/MS. Our findings provide a pathophysiology relevant pharmacological basis for further researches on IS therapeutic drugs.
Highlights
Ischemic stroke (IS), which accounts for 87% of all cerebral strokes, is a leading cause of neurological morbidity and mortality worldwide (Benjamin et al, 2018)
Inflammation, oxidative stress, acidosis, overload of intracellular calcium, excitotoxicity, free radical injury, cytokine injury, complement activation, blood-brain barrier (BBB) impairment and activation of astrocytes and microglia are key events contributing to IS pathology
The SwissADME database (Daina et al, 2017; Zeng et al, 2021c) was employed to evaluate the phytochemicals according to RO5, a classical set of criteria used to evaluate the drug-likeness of a compound (Lipinski, 2004)
Summary
Ischemic stroke (IS), which accounts for 87% of all cerebral strokes, is a leading cause of neurological morbidity and mortality worldwide (Benjamin et al, 2018). It can be induced by a variety of events, such as cardiac ischemia, occlusion of cerebral small blood vessels and carotid atherosclerosis. Reduced blood flow to the brain causes stress, cell death (necrosis and apoptosis) and loss of neuronal function. Inflammation, oxidative stress, acidosis, overload of intracellular calcium, excitotoxicity, free radical injury, cytokine injury, complement activation, blood-brain barrier (BBB) impairment and activation of astrocytes and microglia are key events contributing to IS pathology
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