Glioblastoma (GBM) is the most common and aggressive tumor of the central nervous system, which has a highly invasive growth pattern, which creates poor prospects for patient survival. Chemotherapy and tumor surgery are limited by anticancer drug resistance and tumor invasion. Evidence suggests that combinations of treatments may be more effective than single drugs alone. Natural polyphenolic compounds have potential as drugs for the treatment of glioblastoma and are considered as potential anticancer drugs. Although these beneficial effects are promising, the efficacy of natural polyphenolic compounds in GBM is limited by their bioavailability and blood-brain barrier permeability. Many of them have a significant effect on reducing the progression of glioblastoma through mechanisms such as reduced migration and cell invasion or chemosensitization. Various chemical formulations have been proposed to improve their pharmacological properties. This review summarizes natural polyphenolic compounds and their physiological effects in glioblastoma models by modulating signaling pathways involved in angiogenesis, apoptosis, chemoresistance, and cell invasion. Polyphenolic compounds are emerging as promising agents for combating the progression of glioblastoma. However, clinical trials are still needed to confirm the properties of these compounds in vitro and in vivo.

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Polyphenols are secondary plant metabolites or organic compounds synthesized by them. In other words, these are molecules that are found in plants. Due to the wide variety of polyphenols and the plants in which they are found, these compounds are divided according to the source of origin, the function of the polyphenols, and their chemical structure; where the main ones are flavonoids. All the beneficial properties of polyphenols have not yet been studied, since this group of substances is very extensive and diverse. However, most polyphenols are known to be powerful antioxidants and have anti-inflammatory effects. Polyphenols help fight cell damage caused by free radicals and immune system components. In particular, polyphenols are credited with a preventive effect that helps protect the body from certain forms of cancer. The onset and progression of tumors may be related directly to oxidative stress, or inflammation. These processes can increase the amount of DNA damage and lead to loss of control over cell division. A number of studies have shown that oxidative stress uncontrolled by antioxidants or an uncontrolled and prolonged inflammatory process increases the risk of developing sarcoma, melanoma, and breast, lung, liver, and prostate cancer. Therefore, a more in-depth study of the effect of polyphenolic compounds on certain signaling pathways that determine the complex cascade of oncogenesis is a promising direction in the search for new methods for the prevention and treatment of tumors.

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