Morusinol exerts anti-glioma activity by targeting the PI3K/AKT/mTOR signaling pathway.

Glioma is a highly aggressive brain tumor with limited treatment options. Natural compounds offer promising therapeutic alternatives due to their safety and low toxicity. Morusinol, a flavonoid from Morus alba, exhibits anti-tumor effects in various cancers, but its role in glioma remains unknown. This study demonstrates that Morusinol significantly inhibits proliferation, migration, invasion, and colony formation of LN229 and U251 glioma cells, with IC50 values around 20 μM. It induces apoptosis by increasing ROS levels and modulating Bcl-2 family proteins and caspase-3 activation. Network pharmacology and molecular docking predict strong binding of Morusinol to key PI3K/AKT pathway components, including p110α, p85α, PDK1, and PTEN. Western blotting confirms that Morusinol suppresses AKT and mTOR phosphorylation, indicating pathway inhibition. Importantly, co-treatment with UCL-TRO-1938, a p110α activator, partially reverses Morusinol-induced suppression of AKT phosphorylation and cell proliferation, supporting target specificity. These results indicate that Morusinol exerts potent anti-glioma effects primarily through inhibition of the PI3K/AKT/mTOR signaling pathway. Our findings highlight Morusinol as a promising natural agent for glioma therapy.