Journal Article

Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons

Dourado, Naiara Silva, Ferreira, Rafael Short, Costa, Silvia Lima, de Almeida, Monique Marylin Alves, da Silva, Victor Diógenes Amaral, Butt, Arthur Morgan, Souza, Cleide dos Santos, David, Jorge Mauricio, Costa, Maria de Fátima Dias, da Silva, Alessandra Bispo, David, Juceni Pereira

2020

Overview

Inflammation and oxidative stress are common aspects of most neurodegenerative diseases in the central nervous system. In this context, microglia and astrocytes are central to mediating the balance between neuroprotective and neurodestructive mechanisms. Flavonoids have potent anti-inflammatory and antioxidant properties. Here, we have examined the anti-inflammatory and neuroprotective potential of the flavonoid agathisflavone (FAB), which is derived from the Brazilian plant Poincianella pyramidalis, in in vitro models of neuroinflammation. Cocultures of neurons/glial cells were exposed to lipopolysaccharide (LPS, 1 µg/mL) or interleukin (IL)-1β (10 ng/mL) for 24 h and treated with FAB (0.1 and 1 µM, 24 h). FAB displayed a significant neuroprotective effect, as measured by nitric oxide (NO) production, Fluoro-Jade B (FJ-B) staining, and immunocytochemistry (ICC) for the neuronal marker β-tubulin and the cell death marker caspase-3, preserving neuronal soma and increasing neurite outgrowth. FAB significantly decreased the LPS-induced microglial proliferation, identified by ICC for Iba-1/bromodeoxyuridine (BrdU) and CD68 (microglia M1 profile marker). In contrast, FAB had no apparent effect on astrocytes, as determined by ICC for glial fibrillary acidic protein (GFAP). Furthermore, FAB protected against the cytodestructive and proinflammatory effects of IL-1β, a key cytokine that is released by activated microglia and astrocytes, and ICC showed that combined treatment of FAB with α and β estrogen receptor antagonists did not affect NF-κB expression. In addition, qPCR analysis demonstrated that FAB decreased the expression of proinflammatory molecules TNF-α, IL-1β, and connexins CCL5 and CCL2, as well as increased the expression of the regulatory molecule IL-10. Together, these findings indicate that FAB has a significant neuroprotective and anti-inflammatory effect in vitro, which may be considered as an adjuvant for the treatment of neurodegenerative diseases.

• Publisher: MDPI AG,MDPI
• Subject: agathisflavone / Anti-Inflammatory Agents - pharmacology / Anti-Inflammatory Agents - therapeutic use / anti-neuroinflammation / Antioxidants / Astrocytes / Axonogenesis / Biflavonoids - pharmacology / Biflavonoids - therapeutic use / Bromodeoxyuridine / Caspase-3 / Cell death / Central nervous system / Coculture Techniques / Connexins / Cytokines / Flavonoids / Genotype & phenotype / Glial cells / Glial fibrillary acidic protein / Humans / Immunocytochemistry / Immunoglobulins / Inflammation / Inflammation - chemically induced / Inflammation - drug therapy / Inflammation - pathology / Interleukin 10 / Interleukin-1beta - pharmacology / Lipopolysaccharides / Lipopolysaccharides - pharmacology / Microglia / Monocyte chemoattractant protein 1 / Neurodegenerative diseases / Neuroglia - drug effects / Neuroglia - pathology / Neuronal-glial interactions / Neurons / Neurons - drug effects / Neurons - pathology / Neuroprotection / NF-κB protein / Nitric oxide / Oxidative stress / Phenols / Phytoestrogens - pharmacology / Phytoestrogens - therapeutic use / Tubulin