Natural Anti-Inflammatory Agents in the Chemoprevention of Gliomas: Targeting Neuroinflammation and the Tumor Microenvironment.

Chronic inflammation is a well-established hallmark of cancer, playing a critical role in the initiation and progression of gliomas. Recent evidence underscores the importance of anti-inflammatory natural products as chemotherapeutic and potentially as chemopreventive agents, offering a safe and multifaceted approach to mitigate tumor-promoting inflammation in the brain. This review explores the interplay between major inflammation-related pathways-such as NF-κB, COX-2, and the NLRP3 inflammasome-and key bioactive compounds derived from natural sources such as polyphenols, isothiocyanates, terpenes/lignans, and omega-3-derived mediators. We provide evidence on the effect of these compounds on the above inflammatory triangle. We discuss emerging in vitro, in vivo preclinical and translational evidence in the context of glioma biology and highlight how these compounds may pass the blood-brain barrier (BBB) and modulate the tumor microenvironment (TME), including immune cell infiltration and cytokine profiles that may act in a pro- or anti-inflammatory manner, highlighting their capacity to inhibit GBM-associated inflammation. Each substance may differentially influence the components of the inflammatory triangle. Overall, we position these agents as low-toxicity, formulation-aware adjuncts to standard care. The ultimate goal is offering novel insights on low-toxicity, inflammation-targeting interventions against malignant brain tumors.