7‑Methoxyneochaejasmin A from Stellera chamaejasme induces ROS‑mediated DNA damage and suppresses RAD51‑dependent repair to exert anti-glioma effects.

Gliomas represent the most common primary malignant tumours of the central nervous system and are associated with an extremely poor prognosis; current treatment options are limited in terms of effectiveness. The present study identified a series of monomers with the potential to serve as effective and low-toxicity natural anti-glioma drug candidates. This was achieved by isolating the monomer 7-methoxyneochaejasmin A from the ethyl acetate fraction of Stellera chamaejasme L. This compound has been shown to inhibit the proliferation of U87 and U251 glioma cells in a concentration-dependent manner, block the cell cycle, and induce apoptosis in vitro. Its mechanism of action involves the induction of excessive accumulation of reactive oxygen species (ROS) within cells, causing severe double-strand DNA damage, while simultaneously inhibiting RAD51-mediated homologous recombination repair, thereby exacerbating the irreversible accumulation of DNA damage, and ultimately activating caspase-dependent apoptotic pathways. Nude mouse tumour xenograft experiments confirmed that 7-methoxyneochaejasmin A significantly inhibits glioma growth, downregulates the expression of the proliferation marker Ki-67, and activates apoptotic pathways in vivo. In summary, as the core active component responsible for the antiglioma activity of Stellera chamaejasme L., 7-methoxyneochaejasmin A is a promising drug candidate for the treatment of glioma. As shown in the present study, 7-methoxyneochaejasmin A exerts its antitumour effects in vitro and in vivo through induction of DNA damage and the inhibition of its repair. It possesses considerable potential for pharmaceutical translation and provides experimental evidence for the clinical treatment of gliomas and the development of natural medicines.