San Hua Tang (SHT) was first mentioned in the book "The Collection of Plain Questions about Pathogenesis, Qi, and Life." SHT has the effect of dispelling wind and dredging collaterals, dredging viscera, and guiding stagnation, and is used in the treatment of ischemic stroke (IS). SHT is composed of Rheum palmatum L., Magnolia officinalis Rehder & E.H.Wilson, Citrus assamensis S.Dutta & S.C.Bhattacharya, and Notopterygium tenuifolium M.L.Sheh & F.T.Pu, which is the traditional prescription of the Tongxia method for the treatment of stroke. Tongxia is one of the "eight methods" used in traditional Chinese medicine, which plays a role in treating diseases by promoting gastrointestinal peristalsis and defecation. Studies have demonstrated a close relationship between gut microbiota metabolism and cerebral stroke; however, the role of SHT in IS treatment through gut microbiota or intestinal metabolites is unclear. To explore the connotation of the Xuanfu theory and clarify the mechanism underlying SHT-mediated opening Xuanfu methods. Through metabolomics, 16S rRNA gene sequencing, and molecular biology techniques, research on the changes in the gut microbiota and blood-brain barrier (BBB) will highlight greater strategies for the treatment of stroke. We used pseudo-germ-free (PGF) rats combined with an ischemia/reperfusion (I/R) rat model for the follow-up experimental research. PGF rats were prepared by the intragastric administration of an antibiotic cocktail for 6 days, following which SHT was administered for 5 consecutive days. The I/R model was performed 1 day following the concluding administration of SHT. We detected the neurological deficit score, cerebral infarct volume, serum inflammatory factor levels (interleukin IL-6, IL-10, IL-17, and tumor necrosis factor alpha), tight junction-related proteins (Zonula occludens-1, Occludin, and Claudin-5), and small glue plasma cell-associated proteins (Cluster of Differentiation 16/Cluster of Differentiation 206, Matrix metalloproteinase, ionized calcium-binding adapter molecule 1, and C-X3-C Motif Chemokine Ligand 1) 24 h following I/R. Using 16S rRNA gene sequencing and non-targeted metabolomics analysis, we explored the relationship between fecal microecology and serum metabolites. Eventually, we analyzed the correlation between the gut microbiota and plasma metabolic profile as well as the mechanism underlying the SHT-mediated regulation of gut microbiota to protect the BBB following stroke. In IS treatment, SHT is principally involved in reducing neurological injury and the volume of cerebral infarction; protecting the intestinal mucosal barrier; increasing the levels of acetic acid, butyric acid, and propionic acid; promoting the transformation of microglia to the M2 state; reducing inflammatory reactions; and enhancing tight junctions. These therapeutic effects were not observed in the group treated with antibiotics alone or that treated with SHT in combination with antibiotics, thereby indicating SHT plays a therapeutic role through the gut microbiota. SHT regulates the gut microbiota, inhibits pro-inflammatory factors in rats with IS, alleviates an inflammatory injury of the BBB, and plays a protective role in the brain.

Vascular dementia (VaD) is the second most common type of dementia after Alzheimer's disease, imposing a substantial burden on global health. Accumulating evidence indicates that oxidative stress, characterized by an imbalance between reactive oxygen species (ROS) production and antioxidant defense, plays a pivotal role in the pathogenesis of VaD. This review aims to summarize the latest research progress on the involvement of oxidative stress in the pathogenesis of VaD and explore emerging therapeutic strategies targeting oxidative stress. Oxidative stress is deeply involved in multiple pathological processes of VaD. Its root cause lies in chronic cerebral hypoperfusion (CCH), which leads to mitochondrial dysfunction and excessive ROS production. Such oxidative damage exacerbates blood-brain barrier (BBB) disruption, neuroinflammation, and neuronal apoptosis, ultimately resulting in cognitive decline. Key molecular mechanisms include the activation of NADPH oxidase, impairment of the Nrf2 antioxidant pathway, and dysregulation of SIRT1. Therapeutic strategies have evolved from traditional antioxidants (e.g., α-lipoic acid) to novel approaches, including targeting the Nrf2/HO-1 pathway (e.g., using saffron-rich GJ-4 extract), regulating mitochondrial function, utilizing natural compounds (e.g., resveratrol acting via SIRT1 activation), and non-pharmacological interventions such as acupuncture. These strategies alleviate oxidative stress through multi-target mechanisms and have demonstrated significant efficacy. The central role of oxidative stress in VaD provides new targets for treatment, but a shift from single-target antioxidant therapy to multi-level intervention is required. Future research should focus on developing targeted antioxidant therapies, exploring combination treatment regimens, and validating biomarkers applicable for early detection and therapeutic efficacy assessment.

We used network pharmacology to predict the correlation between the pathway of Bushenhuoxue formula in the treatment of vascular dementia and carried out experiments to verify the correlation between drug composition and disease. By screening the active components and key targets through various databases and drawing the topological network diagram, we obtained 502 effective compound targets, 601 disease targets, 95 disease-related compound targets, and 162 pathways. The pathway related to vascular dementia may be neurodegeneration-multiple diseases, PI3K-Akt signaling pathway, Mitogen-activated protein kinase signaling pathway, or HIF-1 signaling pathway. By detecting the learning and memory ability of vascular dementia rats, the morphology of the hippocampus under the electron microscope, the degree of neuronal damage, and autophagy-related proteins, the results showed that the Bushenhuoxue formula could improve the neuronal injury induced by ischemia in the hippocampus, down-regulate the level of autophagy, and thereby improve learning and memory. Therefore, the Bushenhuoxue formula may improve the ischemic injury of neurons by regulating the mechanism of neuronal autophagy.