Produtos naturais como potenciais agentes terapêuticos para o glioblastoma e neuroinflamação: estudos in vitro e in vivo

Abstract

Natural products play an important role in the prevention and cure of diseases, originating from various sources, such as plants. Among them, we highlight the isolated compound Tannic Acid and the Cecropia pachystachya (CEC) plant. Also, the hydroalcoholic extract of CEC has among its major compounds C-glycosylated and O-glycosylated flavonoids, from which a flavonoid Enriched Fraction (FEF) was developed and used in the present study. The cited compounds present biological activities well described in the literature, mainly against the Central Nervous System (CNS). The central nervous system (CNS) encompasses several diseases, including diseases that involve neuroinflammation processes, such as cancer. Among the tumors, glioblastoma (GB) stands out, a highly aggressive tumor with a treatment that remains palliative. Considering the therapeutic limitation, it is extremely important to search for new targets that aim at a better prognosis and better quality of life for patients. In view of this, in this work we evaluated the in vivo antiglioma effect, the antitumor activity of CEC extract and FEF in vitro and the neuroprotective effect of CEC extract and FEF in a model of LPS-induced neuroinflammation. Our in vitro results demonstrated a reduction in cell viability and proliferation both from treatment with CEC extract and its FEF. In addition, we can observe changes in cell migration of C6 and U87. As for the preclinical model, there was a reduction in tumor size both in animals treated for 15 days with TA (50 mg/kg/day) and with CEC extract (200 mg/kg/day), in addition to modulating oxidative stress parameters and altering purinergic signaling. In addition, in the in vivo model of neuroinflammation, we observed a neuroprotective effect in animals treated for 14 days with the CEC extract (200 mg/kg/day) and its FEF (50 and 100 mg/kg/day) against behavioral parameters, in the modulation of redox status and changes in TNF-α levels. In view of this, our results demonstrate a potential antiglioma effect of TA and CEC extract in modulating pathways that are related to tumor progression, in addition to a potential neuroprotective effect of CEC extract and its FEF on parameters associated with the neuroinflammation process, thus being important targets in the treatment of these diseases.