Neuroimmunomodulatory Properties of Flavonoids and Derivates: A Potential Action as Adjuvants for the Treatment of Glioblastoma

Abstract

Glioblastomas (GBMs) are tumors that have a high ability to migrate, invade and proliferate in the healthy tissue, what greatly impairs their treatment. These characteristics are associated with the complex microenvironment, formed by the perivascular niche, which is also composed of several stromal cells including astrocytes, microglia, fibroblasts, pericytes and endothelial cells, supporting tumor progression. Further microglia and macrophages associated with GBMs infiltrate the tumor. These innate immune cells are meant to participate in tumor surveillance and eradication, but they become compromised by GBM cells and exploited in the process. In this review we discuss the context of the GBM microenvironment together with the actions of flavonoids, which have attracted scientific attention due to their pharmacological properties as possible anti-tumor agents. Flavonoids act on a variety of signaling pathways, counteracting the invasion process. Luteolin and rutin inhibit NFκB activation, reducing IL-6 production. Fisetin promotes tumor apoptosis, while inhibiting ADAM expression, reducing invasion. Naringenin reduces tumor invasion by down-regulating metalloproteinases expression. Apigenin and rutin induce apoptosis in C6 cells increasing TNFα, while decreasing IL-10 production, denoting a shift from the immunosuppressive Th2 to the Th1 profile. Overall, flavonoids should be further exploited for glioma therapy.

A Novel CRISPR/Cas9 Screening Potential Index for Prognostic and Immunological Prediction in Low-Grade Glioma

“…Since considerable alterations occur in the tumor microenvironment, which is tightly associated with immunotherapeutic efficiency ( Codrici et al, 2022 ), varied treatments would be recommended for C1 and C2. For example, previous evidence showed that the microenvironment formed by the perivascular niche and composed of endothelial cells was correlated with tumor progression ( do Nascimento et al, 2022 ) and activation of cytotoxic cells contributed to the mortality of cancer cells ( Miyauchi and Tsirka, 2018 ). Hence regulating immune components or targeting stromal cells might be more applicable in C1.…”

Exploring the potential role of genus Sophora in the management of osteoporosis: a phytochemical and biological review

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