期刊
BIOMOLECULES
卷 10, 期 4, 页码 -出版社
MDPI
DOI: 10.3390/biom10040562
关键词
flavonoids; agathisflavone; neuroprotection; anti-neuroinflammation
资金
- Coordination of Personnel Improvement of Higher Level (CAPES) [88881.117666/2016-01, 88881.133939/2016-01]
- Foundation for Research Support of the State of Bahia [INT 0016/2016]
- National Council for Scientific and Technological Development (CNPq) [MCTI/CNPq/Universal 14/2014, 443723/2014-1, 140333/2016-9]
- BBSRC [BB/M029379/1]
- BBSRC [BB/M029379/1] Funding Source: UKRI
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 mu g/mL) or interleukin (IL)-1 beta (10 ng/mL) for 24 h and treated with FAB (0.1 and 1 mu M, 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 beta-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-1 beta, a key cytokine that is released by activated microglia and astrocytes, and ICC showed that combined treatment of FAB with alpha and beta estrogen receptor antagonists did not affect NF-kappa B expression. In addition, qPCR analysis demonstrated that FAB decreased the expression of proinflammatory molecules TNF-alpha, IL-1 beta, 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.
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