Antineuroinflammatory Effect of Amburana cearensis and Its Molecules Coumarin and Amburoside A by Inhibiting the MAPK Signaling Pathway in LPS-Activated BV-2 Microglial Cells

Abstract

Microglia plays an important role in the neuroinflammatory response, identified as one of the major factors in the development and progression of neurodegenerative diseases. Amburana cearensis and its bioactive compounds, including coumarin (CM), vanillic acid (VA), and amburoside A (AMB), exert antioxidant, anti-inflammatory, and neuroprotective activities, on 6-OHDA-induced neurotoxicity in rat mesencephalic cells determined by our group. The present study investigated the anti-inflammatory effect of the dry extract from A. cearensis (DEAC), CM, AMB, and VA on lipopolysaccharide- (LPS-) stimulated microglial cells and elucidated the possible molecular mechanism of action. The DEAC was characterized by HPLC-PDA (chemical markers: CM, AMB, and VA). The BV-2 microglial cell line was pretreated with increasing concentrations of DEAC, CM, AMB, or VA in the presence or absence of LPS to evaluate the toxicity and anti-inflammatory activity. The cytotoxicity of DEAC, CM, AMB, or VA on BV-2 cells was evaluated by the MTT test, the free radical scavenging activity of test drugs was investigated, and the nitric oxide (NO) production was determined using the Griess reagent, while cytokine levels were measured by ELISA. The expressions of toll-like receptor 4 (TLR-4), nuclear factor kappa B (NF-κB), MAPK members (JNK and ERK1/2), and iNOS were determined through Western blot analysis. DEAC, CM, AMB, or VA (5-100 μg/mL) did not induce any detectable cytotoxicity in BV-2 cells. All test drugs (100 μg/mL) showed free radical scavenging activity (hydroxyl and superoxide radicals); however, only DEAC, CM, and AMB (5-100 μg/mL) significantly reduced NO production. DEAC (100 μg/mL), as well as CM (50 and 100 μg/mL) and AMB (25 μg/mL), reduced at least 50% of NO produced and markedly decrease the production of TNF-α and IL-6 but they did not significantly affect IL-10 levels. Only DEAC (100 μg/mL) and AMB (25 μg/mL) reduced the expression of iNOS, and they did not affect arginase activity. DEAC (100 μg/mL) suppressed the activation of the MAPKs JNK and ERK1/2 in LPS-activated BV-2 cells but it did not suppress the expression of TLR-4 nor the phosphorylation of NF-κB. In conclusion, DEAC, CM, and AMB exerted anti-inflammatory activity in LPS-activated microglial cells as observed by the reduction in the production of inflammatory mediators and the expression of iNOS. We identified the MAPK signaling pathway as a probable mechanism of action to the anti-inflammatory effects observed.

Knowledge mapping of links between dendritic cells and allergic diseases: A bibliometric analysis (2004–2023)

“…Vanillic acid, an oxidized form of vanillin, is a phenolic antioxidant which has been reported with numerous pharmacological properties incluing anti-inflammatory [ 49 , 85 ]. According to more than one study, vanillic acid can decrease the expression of inflammatory markers incluing TLRs [ 86 , 87 ]. Though there was not the direct research between TLRs and the components of prim- O -glucosylcimifugin and 5- O -methylvisammioside, the function in anti-allergy of prim- O -glucosylcimifugin and 5- O -methylvisammioside has been reported more than once [ [53] , [54] , [55] , [56] ].…”

Assessing the role of primary healthy microglia and gap junction blocker in hindering Alzheimer’s disease neuroinflammatory type: Early approaches for therapeutic intervention

“…This is followed by activation of the NF-κB and MAP kinase pathways, leading to the release of inflammatory cytokines and apoptosis. The liberated inflammatory and apoptotic factors cause direct damage to different areas of the brain and spinal cord, including Aβ toxic aggregates (Batista et al, 2019;de Araújo et al, 2022). It was previously reported that the degree of neuropathological damage induced by Detection of glial fibrillary acidic protein (GFAP) expression level in the cerebral cortex (A) and the spinal cord (B) of the lipopolysaccharide (LPS)-induced rats and following the single intracerebroventricular (ICV) administration of primary healthy microglia (PHM) and carbenoxolone (CBX) (week 3).…”

“…This is followed by activation of the NF-κB and MAP kinase pathways, leading to the release of inflammatory cytokines and apoptosis. The liberated inflammatory and apoptotic factors cause direct damage to different areas of the brain and spinal cord, including Aβ toxic aggregates ( Batista et al, 2019 ; de Araújo et al, 2022 ). It was previously reported that the degree of neuropathological damage induced by neuroinflammation is mainly controlled by the type of activated microglial phenotype.…”