Is it possible that hyperactivation of microglia results in brain inflammation? Microglia was found to play a major role in the neurodegenerative diseases like: Parkinson, AD, Addiction, Alzheimer, ADHD, OCD, etc, Then reducing the neuroinflammation might be a preventative step or slow down of neurodegenerative disease. Or maybe consuming diet rich in antioxidants, polyphenols help reduce brain inflammation?  Studies shows that the molecular mechanism of the plant antioxidant extracts leads to inhibition of phosphorylation of nitrogen activated protein kinase (MAPKs) extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38 MAPK and activation of nuclear factor kappa B (NF-KappaB). Maybe manipulating migroglial metabolism may modulate neuroinflammation?

Studies suggest that dysregulation of glutamate is involved in neuroinflammation and microglia expresses glutamate receptors (GluRs) which are both metabotropic and ionotropic. Dyregulation of glutamate signaling is important in neurodegenerative disease and microglia modulate both metabotropic and ionotropic the glutamate receptors. Microglia lacking GlutA2 shows higher Ca (2+) permeability increasing pro inflammatory cytokine such as TNF alpha. In neurodegenerative disease is associated with decreased expression of GluA2 via proinflammatory cytokines from microglia.

Polyphenols from medicinal plants have an anti inflammatory properties and might mediate the NF-kB neuroinflammation. Studies suggest that polyphenols like hesperetin, allium sativum, ginger rice extract and silibinin migh modulate microglia.

Neural Regen Res. 2020 May;15(5):838-842. doi: 10.4103/1673-5374.268897. Regional brain susceptibility to neurodegeneration: what is the role of glial cells? Cragnolini AB1, Lampitella G2, Virtuoso A2, Viscovo I2, Panetsos F3, Papa M2, Cirillo G2. Retrieved from:

Hesperetin, a Citrus Flavonoid, Attenuates LPS-Induced Neuroinflammation, Apoptosis and Memory Impairments by Modulating TLR4/NF-κB Signaling. Muhammad T1, Ikram M2, Ullah R3, Rehman SU4, Kim MO5. Retrieved from:

Curr Alzheimer Res. 2016;13(4):381-6. Dysfunction of Glutamate Receptors in Microglia May Cause Neurodegeneration. Noda M1.Int J Mol Sci. 2019 Feb 7;20(3). pii: E708. doi: 10.3390/ijms20030708. Retrieved from:

Anti-Inflammatory Activity of A Polyphenolic Extract from Arabidopsis thaliana in In Vitro and In Vivo Models of Alzheimer’s Disease. Mattioli R1, Francioso A2,3, d’Erme M4, Trovato M5, Mancini P6, Piacentini L7, Casale AM8, Wessjohann L9, Gazzino R10, Costantino P11, Mosca L12. Retrieved from:

Neurotox Res. 2019 Dec 10. doi: 10.1007/s12640-019-00147-2. [Epub ahead of print] NF-κB-Mediated Neuroinflammation in Parkinson’s Disease and Potential Therapeutic Effect of Polyphenols. Singh SS1, Rai SN1, Birla H1, Zahra W1, Rathore AS1, Singh SP2. Retrieved from:

Neurotoxicology. 2018 Mar;65:85-97. doi: 10.1016/j.neuro.2018.02.001. Epub 2018 Feb 6.Agathisflavone, a flavonoid derived from Poincianella pyramidalis (Tul.), enhances neuronal population and protects against glutamate excitotoxicity. Dos Santos Souza C1, Grangeiro MS1, Lima Pereira EP1, Dos Santos CC1, da Silva AB1, Sampaio GP1, Ribeiro Figueiredo DD2, David JM3, David JP2, da Silva VDA1, Butt AM4, Lima Costa S Retrieved from:

J Neuroinflammation. 2016 Jun 14;13(1):148. doi: 10.1186/s12974-016-0615-6. Rice bran derivatives alleviate microglia activation: possible involvement of MAPK pathway. Bhatia HS1,2, Baron J3, Hagl S4, Eckert GP4,5, Fiebich BL3, Retrieved from:

Neuromolecular Med. 2016 Sep;18(3):474-82. doi: 10.1007/s12017-016-8410-1. Epub 2016 Jun 4.Protective Effects of AGE and Its Components on Neuroinflammation and Neurodegeneration.Qu Z1,2, Mossine VV3, Cui J1,2,4, Sun GY1,2,3, Gu Z5,6,7 Retrieved from :