Progress on the functions and mechanisms of natural products in anti-glioma therapy

Glioma, the most prevalent primary tumor of the central nervous system (CNS), is the most lethal primary malignant tumor. Until now, there are limited chemotherapeutics to treat gliomas. Therefore, more researches are needed to find and explore new chemotherapeutic drugs for the treatment of gliomas. Discovering anti-tumor active ingredients from natural products (NPs) and optimizing their structures would be a significant way to discover anti-glioma drugs. In addition, targeted drug delivery systems (TDDSs) are used to improve drug solubility and stability and overcome the blood-brain barrier (BBB). TDDSs can reach the deep brain, increase the concentration and retention time of drugs in CNS, enhance the targeting efficiency of NPs thus decreasing the adverse effect to improve the anti-glioma effect. In this paper, the research progress of anti-glioma activities of NPs including alkaloids, polyphenols, flavonoids, terpenoids, saponins, quinones as well as their synthetic derivatives in the past decade are reviewed. The anti-glioma mechanisms including suppression of related protein expression, regulation of reactive oxygen species (ROS) levels, control of apoptosis signaling pathways, reduction of matrix metalloproteinases (MMPs) expression, blocking of vascular endothelial growth factor (VEGF), and reversing immunosuppression are also summarized. Furthermore, the functions and advantages of natural product-based TDDSs in anti-glioma therapy have been reviewed. All these key information in this review will be valuable for the research and development of natural product-based anti-glioma drugs and related TDDSs.