Neuroprotective Effects of Rhodiola rosea and Ligusticum chuanxiong Decoction (FC1) Against Ischemic Stroke

Abstract

Ischemic stroke is one of the main causes of morbidity and death worldwide, characterized by a reduction in cerebral blood flow that results in neuronal damage and functional impairment. Unfortunately, current treatment options are primarily focused on thrombolytic therapy and rehabilitative care, without fully addressing causes of secondary tissue damage, such as excitotoxicity and oxidative stress. Rhodiola rosea L. and Ligusticum chuanxiong Hort. are both commonly used herbs for the treatment of circulation-related disorders, including ischemic stroke. While decoctions combining these two herbs have been prescribed in traditional Chinese medicine, the effectiveness and mechanisms of the herbal combination in the context of ischemic stroke have yet to be studied. To verify the effectiveness of the two-herb (FC1) decoction in ischemic stroke injury and to investigate the underlying mechanisms behind its neuroprotective effect, we performed mouse focal cerebral ischemia/reperfusion (I/R) injury through the middle cerebral artery occlusion (MCAO) model. Mice were administered either FC1 or vehicle before MCAO, then their cerebral infarct, neurological deficits and survival rates were evaluated. FC1 effectively protects MCAO mice against I/R injury, reducing infarct size, improving survival rate and motor function recovery. Proteome analysis of brain tissue also revealed that FC1 regulates pathways involved in respiratory complex I metabolism, ion homeostasis and oxidative stress. Additionally, primary rat cortical neurons were pre-treated with FC1 or vehicle to examine their survival and mechanisms against N-methyl-D-aspartate (NMDA)-induced excitotoxicity, which was found to confer neuroprotection against NMDA excitotoxicity. Furthermore, FC1 reduces excitotoxic neuronal damage by attenuation of mitochondrial superoxide production and intracellular Ca²⁺ influx, while maintaining mitochondrial membrane potential and ATP production. Overall, our results demonstrate that this herb-pair decoction has therapeutic potential in alleviating ischemic stroke injury and attenuating cellular damage caused by excitotoxicity, through the protection of critical mitochondrial functions.

Date of Award	2025
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Nancy Yuk-Yu IP (Supervisor)