Abstract
Microglial cells play a dual role in the central nervous system as they have both neurotoxic and neuroprotective effects. Uncontrolled and excessive activation of microglia often contributes to inflammation-mediated neurodegeneration. Recently, much attention has been paid to therapeutic strategies aimed at inhibiting neurotoxic microglial activation. Pharmacological inhibitors of microglial activation are emerging as a result of such endeavors. In this review, natural products-based inhibitors of microglial activation will be reviewed. Potential neuroprotective activity of these compounds will also be discussed. Future works should focus on the discovery of novel drug targets that specifically mediate microglial neurotoxicity rather than neuroprotection. Development of new drugs based on these targets may require a better understanding of microglial biology and neuroinflammation at the molecular, cellular, and systems levels.
Highlights
Inflammation in the brain and the rest of the central nervous system (CNS) is a key factor in neurodegenerative diseases
In the event of brain damage or infection, microglia cells become activated and may secrete a variety of inflammatory mediators and neurotoxic factors. In this condition, activated microglia cells trigger and maintain an inflammatory response, deluging neurons with a whole host of inflammatory mediators that may lead to neuronal cell death
Resveratrol has been shown to inhibit the activation of microglia and reduce the production of pro-inflammatory factors through intracellular cascades of signaling pathways such as mitogen-activated protein kinases (MAPKs), phosphoinositide3-kinase (PI3-K)/Akt, and glycogen synthase kinase-3β (GSK-3β) pathways
Summary
Inflammation in the brain and the rest of the central nervous system (CNS) is a key factor in neurodegenerative diseases. In the event of brain damage or infection, microglia cells become activated and may secrete a variety of inflammatory mediators and neurotoxic factors. Several methods have become available for identifying activated microglia, and their presence has been demonstrated in a variety of neuroinflammatory/neurodegenerative diseases such as AD, PD, ALS and multiple sclerosis (MS) [9,10,11]. This participation of activated microglia and the release of neurotoxic products in the demise of neurons have been postulated in most, if not all, neurodegenerative diseases. The traditional herbal medicines with dependable ethnopharmacological properties have recently been demonstrated to possess neurotrophic and neuroprotective abilities, which can be useful in preventing various forms of neuronal cell loss in neurodegenerative and neuroinflammatory diseases. We will focus on popular and important natural products and their active constituents as well as their anti-inflammatory activities based on inhibiting microglial activation
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