Houshiheisan, a classic prescription for stroke treatment, originates from Chapter 5 on Pulse Syndrome Complex and Treatment of Apoplexy and Acute Arthritis of Synopsis of Golden Chamber, which discusses pulse syndrome complex and apoplexy and acute arthritis treatment. Renowned as a primary prescription for stroke, it exemplifies the therapeutic principle of tonifying deficiencies while reducing excesses. This study showed that Houshiheisan improves hemorheology, reduces oxidative damage, protects neurovascular units after cerebral ischemic injury, promotes neovascularization maturation, and maintains cerebrovascular endothelial barrier integrity. Based on the pathogenesis theory of stroke, which is the cause of internal deficiency and pathogenic factor invasion, studies on Houshiheisan disassembling were conducted. The herbs in the prescription were divided into wind-dispelling herbs such as Flos Chrysanthemi, Radix Saposhnikoviae, and Ramulus Cinnamomi and deficiency-tonifying herbs such as Radix Ginseng, Radix Angelicae Sinensis, and Rhizoma Atractylodis Macrocephalae. Wind-dispelling herbs primarily reduced cerebral ischemia injury by downregulating Caspase-3 expression, an apoptotic protein, and deficiency-tonifying herbs reduced cerebral ischemia by upregulating poly ADP-ribose polymerase expression, a DNA repair protein. Wind-dispelling herbs exhibited a rapid yet short-lived effect by significantly downregulating aquaporin-4 (AQP4) expression in the lateral ventricle six hours after cerebral ischemia. In contrast, deficiency-tonifying herbs showed a delayed but sustained regulatory impact on AQP4 expression. These complementary time-dependent effects reflect the dual function of the prescription of dispelling wind and tonifying deficiencies, aligning well with the early pathogenesis of cerebral small vessel disease, which is characterized by wind-phlegm and blood stasis obstructing the brain collaterals. Additionally, Houshiheisan reduces blood pressure and blood lipids, improves patients′ hemorheology, and alleviates vascular endothelial cell dysfunction. Therefore, Houshiheisan is a safe and effective classic prescription for preventing and treating early cerebral small vessel disease. Future research should focus on exploring its molecular mechanisms in treating cerebral small vessel diseases.

Houshiheisan;wind-dispelling herbs;deficiency-tonifying herbs;cerebral small vessel disease