Myricitrin blocks activation of NF-κB and MAPK signaling pathways to protect nigrostriatum neuron in LPS-stimulated mice

Abstract

Myricitrin, a bioactive and natural flavonoids, is well known for its anti-inflammatory and antioxidant properties. However, the anti-neuroinflammation and possible mechanism has not been fully elucidated. Therefore, the present study was to investigate the possible mechanism of its neuroprotection and anti-neuroinflammation in the nigrostriatum of LPS-stimulated mice. The results showed that myricitrin improved neuron injury and raised the expressions of PSD-95 protein and TH protein in the nigrostriatum of LPS-stimulated mice. In addition, myricitrin decreased the production of pro-inflammatory factors including IL-1β, IL-6 and TNFα, decreased the level of chemokine MCP-1, and suppressed the expressions of COX-2 and iNOS. Meanwhile, myricitrin suppressed HMGB1, TLR4, and MyD88 expression in the nigrostriatum of LPS-stimulated mice. Furthermore, myricitrin inhibited NF-κB and MAPK signaling pathways activated by LPS. In conclusion, our studies suggest that myricitrin blocks activation of protects NF-κB and MAPK signaling pathways to nigrostiatum neuron from injury in LPS-stimulated mice and is beneficial to treatment nigrostriatum inflammation of PD.

Myricetin Ameliorates Ox-LDL-induced HUVECs Apoptosis and Inflammation via lncRNA GAS5 Upregulating the Expression of miR-29a-3p

“…Myr treatment can reverse these effects. A previous study showed that Myr inhibited the HMGB1, TLR4, and MyD88 expressions in the neurons, and it restored neuronal damage and in ammation caused by activation of NF-κB and MAPK signal pathways [28]. In this study, up-regulation of lncRNA GAS5 and down-regulation of miR-29a-3p led to a decrease of cell apoptosis, in ammation, and EndMT, as well as reduction of activity of TLR4/NF-κB signaling pathway.…”

Phytochemicals with Added Value from Morella and Myrica Species

“…The results presented by Domitrovic et al [73] suggest that the anti-inflammatory and antioxidant effects of myricitrin (10) are responsible for its hepatoprotective activity. In fact, all the myricitrin (10) in vivo studies presented in Table 2 strongly indicate that 10 exerts its protective effects through the blockage of inflammation, oxidative stress, and apoptosis [44,45,73,74], which confirms myricitrin (10) as a potential candidate for the treatment and prevention of a wide array of disorders related to oxidative stress and inflammation.…”

“…In addition, myricitrin (10) decreased the production of pro-inflammatory factors including IL-1β, IL-6, and TNFα, decreased the level of chemokine MCP-1, and suppressed the expressions of COX-2 and iNOS (Table 2). Meanwhile, myricitrin suppressed HMGB1, TLR4, and MyD88 expression in the nigrostriatum of LPS-stimulated mice, and inhibited NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways activated by LPS [74]. These effects show that myricitrin (10) is efficient in protecting the brain against inflammation and all the nefarious effects it causes.…”

“…Another in vivo study showed that a dosage of 50 mg/kg of myricitrin (10) improved neuron injury and increased the expressions levels of PSD-95 protein and tyrosine hydroxylase TH protein in lipopolysaccharide (LPS)-stimulated BALB/c mice [74]. Loss of these proteins is found in Parkinson's disease [78], so the fact that myricitrin increases their expression hints for a possible role in the prevention of this disease.…”

“…Decrease of Bax/Bcl-2 ratio (35-fold), caspase-3 (5-fold), and caspase-9 (4-fold) expression levels, when compared with the untreated group. BALB/c mice 50 mg/kg Neuroprotective activity[74] In LPS-stimulated mice: 2-fold increase on the expression levels of PSD-95 and TH, when compared with untreated group. Reduction on expression levels of IL-1β (3-fold), IL-6 (2-fold), TNF-α (2-fold), and MCP-1 (2-fold), when compared with the untreated group.…”