Schisandrin B targets CD44 to inhibit glioblastoma multiforme.

Glioblastoma multiforme (GBM), the most common malignant primary brain tumor, responds poorly to surgery, radiotherapy, chemotherapy, and immunotherapy, with dismal prognosis and short median survival. There is an urgent need for improved therapies, with supportive and palliative care integral to the multimodal treatment strategy. Traditional Chinese medicine (TCM) exerts antitumor effects via multi-target and multi-pathway mechanisms. Thus, screening and validation of candidate natural small molecules for the therapy and adjuvant therapy of glioblastoma multiforme (GBM) are of great significance. In this study, bioinformatics analysis identified cluster of differentiation 44 (CD44) as a positive correlate of glioblastoma multiforme (GBM). Using cluster of differentiation 44 (CD44) protein structure from the AlphaFold Protein Structure Database, we combined network pharmacology, virtual screening, and molecular docking to pinpoint Schisandrin B (Sch B) as a candidate natural small molecule against glioblastoma multiforme (GBM). In vitro assays verified that Schisandrin B (Sch B) potently inhibited glioblastoma multiforme (GBM) cell proliferation, migration, and invasion. In vivo glioblastoma multiforme (GBM) xenograft models confirmed that Schisandrin B (Sch B) reduced tumor volume, improved mouse survival, and enhanced autonomous activity. Safety evaluations further demonstrated that Schisandrin B (Sch B) had no adverse effects on mouse body weight, autonomous activity, organ index, or tissue morphology. Taken together, Schisandrin B (Sch B) targets cluster of differentiation 44 (CD44) to inhibit glioblastoma multiforme (GBM), and it has relatively good safety performance. This study can provide a research foundation for the therapy and adjuvant therapy of glioblastoma multiforme (GBM).