Phytoestrogen Agathisflavone Ameliorates Neuroinflammation-Induced by LPS and IL-1β and Protects Neurons in Cocultures of Glia/Neurons
Monique Marylin Alves de Almeida,
Cleide dos Santos Souza,
Naiara Silva Dourado,
Alessandra Bispo da Silva,
Rafael Short Ferreira,
Jorge Mauricio David,
Juceni Pereira David,
Maria de Fátima Dias Costa,
Victor Diógenes Amaral da Silva,
Arthur Morgan Butt,
Silvia Lima Costa
Affiliations
Monique Marylin Alves de Almeida
Laboratory of Neurochemistry and Cellular Biology, Department of Biophysics and Biochemistry, Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia 40.110-100, Brazil
Cleide dos Santos Souza
Laboratory of Neurochemistry and Cellular Biology, Department of Biophysics and Biochemistry, Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia 40.110-100, Brazil
Naiara Silva Dourado
Laboratory of Neurochemistry and Cellular Biology, Department of Biophysics and Biochemistry, Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia 40.110-100, Brazil
Alessandra Bispo da Silva
Laboratory of Neurochemistry and Cellular Biology, Department of Biophysics and Biochemistry, Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia 40.110-100, Brazil
Rafael Short Ferreira
Laboratory of Neurochemistry and Cellular Biology, Department of Biophysics and Biochemistry, Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia 40.110-100, Brazil
Jorge Mauricio David
Department of General and Inorganic Chemistry, Institute of Chemistry, Federal University of Bahia, Salvador-Bahia 40.170-115, Brazil
Juceni Pereira David
Department of Medication, Faculty of Pharmacy, Federal University of Bahia, Salvador-Bahia 40.170-115, Brazil
Maria de Fátima Dias Costa
Laboratory of Neurochemistry and Cellular Biology, Department of Biophysics and Biochemistry, Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia 40.110-100, Brazil
Victor Diógenes Amaral da Silva
Laboratory of Neurochemistry and Cellular Biology, Department of Biophysics and Biochemistry, Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia 40.110-100, Brazil
Arthur Morgan Butt
School of Pharmacy and Biomedical Science, University of Portsmouth, Portsmouth PO1 2DT, UK
Silvia Lima Costa
Laboratory of Neurochemistry and Cellular Biology, Department of Biophysics and Biochemistry, Institute of Health Sciences, Federal University of Bahia, Salvador-Bahia 40.110-100, Brazil
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.
