Sleep disorders are the most widespread mental disorders after stroke and hurt survivors’ functional prognosis, response to restoration, and quality of life. This review will address an overview of the progress of research on the biological mechanisms associated with stroke-complicating sleep disorders. Extensive research has investigated the negative impact of stroke on sleep. However, a bidirectional association between sleep disorders and stroke exists; while stroke elevates the risk of sleep disorders, these disorders also independently contribute as a risk factor for stroke. This review aims to elucidate the mechanisms of stroke-induced sleep disorders. Possible influences were examined, including functional changes in brain regions, cerebrovascular hemodynamics, neurological deficits, sleep ion regulation, neurotransmitters, and inflammation. The results provide valuable insights into the mechanisms of stroke complicating sleep disorders.

Epimedii Folium (Yinyanghuo), a unique and traditional Chinese medicinal plant used in medicine for more than a thousand years, has been traditionally used to tonify the liver and kidneys, strengthen the muscles and bones, and eliminate rheumatism. Its principal active ingredient, icariin, has long been used clinically for impotence and spermatorrhea, weakness of muscles and bones, rheumatism and arthralgia pain, and has recently attracted growing attention for its therapeutic potential against central nervous system diseases. This review summarizes advances over the past five years in the preparation, neuroprotective effects, and pharmacokinetics of icariin. The literature was retrieved from Pubmed, CNKI (China National Knowledge Infrastructure), Web of Science, and Google Scholar using keywords including “icariin”, “Epimedii Folium”, “neuroprotection”, “biosynthesis” and “pharmacokinetics”, and studies were screened for relevance to preparation methods, pharmacological evaluation, and pharmacokinetic properties. Although extraction from plant sources remains the main preparation method, chemical synthesis and biosynthesis are emerging in response to resource scarcity. Accumulating evidence indicates that icariin exerts neuroprotective effects through multiple mechanisms, including anti-neuroinflammation, mitochondrial protection, antioxidant effects, inhibition of neuronal apoptosis, promotion of neuronal proliferation and differentiation and regulation of synaptic plasticity. Its rapid absorption, ability to cross the blood–brain barrier, and low cumulative toxicity provide a favorable pharmacokinetic basis for central nervous system applications. This review highlights synthetic strategies, pharmacological evaluation and pharmacokinetic characteristics of icariin, aiming to support its broader application in CNSDs.

Pterostilbene (Pts), a small molecule stilbenoid and a dimethyl analogue of the star molecule resveratrol, exerts significant blood–brain barrier protection on cerebral ischemia-reperfusion injury and has received extensive attention. This study performed structural optimizations on Pts to obtain a series of derivatives and investigated their anti-ischemic activities both in vitro and in vivo, aiming to identify candidates with high safety and improved efficacy compared with Pts. The ADMET method was used to predict the drug-likeness of a series of Pts derivatives, and in vitro MTT cell viability analysis was conducted on neuroblastoma cells (SH-SY5Y) and brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation/reperfusion (OGD/R) injury. On the basis of the cytotoxicity results, four derivatives (NO. 1, NO. 3, NO. 5, and NO. 7) were selected for subsequent in vitro and in vivo biological activities evaluation. These compounds exhibited significantly higher TI values (18.29–30.61) in OGD/R-injured hBMECs compared with Pts (7.63) and effectively suppressed apoptosis, promoted cell migration, and enhanced tube formation capacity. In vivo, NO. 3 (5 mg/kg, ip., 7 d) demonstrated superior efficacy compared to Pts in improving cerebral blood flow, reducing infarction volume, enhancing neurological function, and modulating serum biomarker levels in middle cerebral artery occlusion/reperfusion (MCAO/R) rats, whereas NO. 1 and NO. 7 showed comparable efficacy to Pts. The acute intraperitoneal toxicity of NO. 3 was conducted and showed that the LD₅₀ of NO. 3 was estimated to be more than 300 mg/kg. In this study, the rational design and comprehensive evaluation of Pts derivatives were reported. Compound NO. 3 demonstrated superior pharmacological efficacy to Pts both in vitro and in vivo, and it may be a promising therapeutic candidate for ischemic stroke intervention.