Traditional Chinese medicine as a therapeutic option for cerebral small vessel disease: treatment outcomes and potential mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral small vessel disease (CSVD) leads to vascular cognitive impairment, gait disturbances, and disability in later life. Common observations include white matter hyperintensities, lacunar infarcts, increased perivascular gaps, and microhemorrhages. The condition progresses gradually as a result of endothelial and microvascular dysfunction, diminished blood flow, compromised lymphatic clearance, and neuroinflammation. Contemporary medicine has enhanced risk management; yet, no medication substantially postpones disease progression, underscoring the necessity for alternative treatment strategies. Traditional Chinese Medicine (TCM), characterized by its holistic approach and classification of conditions, provides a distinctive perspective on complex diseases, including cerebral small vessel disease. In TCM, theories such as "blood stasis obstructing collaterals", "toxin impairing collaterals" and "kidney deficiency leading to marrow degeneration" are highly consistent with the contemporary pathophysiological theories of CSVD. This review uniquely synthesizes TCM theories with contemporary mechanistic evidence, encompassing clinical trials and network pharmacology, thereby establishing a comprehensive framework for the prospective application of TCM in CSVD and filling a void in prior research in this domain.

AIM OF THE STUDY: This study assesses TCM for CSVD, elucidates its mechanisms of action and clinical efficacy, and synthesizes recent research to evaluate TCM's significance and potential in the management of CSVD.

MATERIALS AND

METHODS

In accordance with the PRISMA guidelines, we conducted a systematic search of major scientific databases (PubMed, Web of Science, Embase, Cochrane Library, Wanfang and CNKI), with the search time range spanning from the establishment of each database to October 2025. Predefined keywords were adopted, including cerebral small vessel disease, white matter hyperintensities, lacunar cerebral infarction, traditional Chinese medicine, Chinese herbal medicine, acupuncture, and traditional Chinese herbal prescriptions. The literatures included in the analysis were qualified original studies (covering clinical trials, observational studies, and experimental studies involving human subjects or animal/cell models). These studies adopted any intervention measures of TCM and reported outcome indicators related to efficacy, mechanisms or safety. Reviews, commentaries and case reports were excluded. Two reviewers independently screened the titles, abstracts and full texts. Discrepancies were resolved through consensus negotiation or by a third reviewer. Standardized forms were used for data extraction. Meta-analysis was not performed due to the significant heterogeneity among the included studies. The quality of clinical studies was evaluated using the Cochrane Risk of Bias Assessment Tool, and the quality of animal studies was assessed with the SYRCLE Risk of Bias Assessment Tool. The evaluation results were applied to assist in interpreting the research findings, rather than serving as the basis for excluding relevant studies.

RESULTS

Based on clinical trials, animal models, and in vitro investigations, this study describes several TCM therapies that may benefit CSVD. These therapies protect the endothelium, stabilize the BBB, reduce neuroinflammation, increase microcirculation, and clear lymphatics. These effects match CSVD's complex pathology, but the research deserves scrutiny. Animal models have shown that TCM formulations regulate vascular homeostasis and reduce white matter injury via PI3K/Akt, NF-κB, and Wnt/β-catenin pathways. These interesting discoveries need clinical validation to be relevant. However, some clinical investigations demonstrate that specific formulations increase cognition and daily life, indicating their therapeutic efficacy, particularly in patients with cognitive impairments or neurodegenerative conditions. Numerous experiments have limited sample sizes and short durations. Modern formulations increase drug absorption and brain targeting, yet most research is preclinical. Mechanisms are diverse, but evidence varies. Confirming these preliminary findings requires larger, more thorough clinical investigations.

CONCLUSION

In conclusion, TCM may target the intricate network associated with persistent stroke-related vascular illness. Specific herbal formulations have demonstrated the ability to enhance endothelial function and diminish blood-brain barrier (BBB)permeability. They additionally mitigate neuroinflammation, enhance hypoperfusion, and facilitate the clearance of metabolic waste. Contemporary formulation techniques improve the precision and efficacy of TCM. Collectively, these data indicate novel approaches for the management of CSVD as a chronic condition. Nonetheless, obstacles in standardization and reproducibility necessitate additional investigation to facilitate clinical translation and wider acceptability.