Elucidating the mechanism of traditional Chinese medicine formula () in alleviating the chemobrain based on network pharmacology and experimental verification.

[BACKGROUND] Cisplatin (DDP) is widely used to treat clinical malignant tumors, but it is also accompanied by serious adverse reactions, such as brain nervous system injury. In clinical treatment and animal experiments, traditional Chinese medicine formula (, YFSJ) has been observed to relieve the symptoms of chemobrain caused by DDP chemotherapy, but its mechanism of action remains unclear.

[METHODS] A subcutaneous model of non-small cell lung cancer was established in mice, which were subsequently treated with YFSJ to evaluate the mechanism by which YFSJ alleviates DDP-induced chemobrain. Specifically, the effects of DDP and YFSJ on the brain nervous system of mice were evaluated by behavioral tests, brain blood flow observation, network pharmacology analysis, and histological analysis. In addition, the damaging effect of DDP on neurons and the effect of YFSJ on neurons were verified by experiments.

[RESULTS] YFSJ reduced systemic inflammation in tumor-bearing mice, restored the function of the blood‒brain barrier (BBB) to reduce the amount of cisplatin in the brain, alleviated the decreases in voluntary activity and brain blood flow microcirculation induced by DDP, and alleviated brain tissue pyroptosis and ferroptosis caused by DDP.

[CONCLUSIONS] YFSJ maintains the functional stability of the BBB by inhibiting tumor-induced inflammation, thereby preventing chemobrain induced by nervous system damage caused by DDP entering brain tissue.