Role of Plant Phytochemicals: Resveratrol, Curcumin, Luteolin and Quercetin in Demyelination, Neurodegeneration, and Epilepsy

Abstract

Polyphenols are an important group of biologically active compounds present in almost all food sources of plant origin and are primarily known for their anti-inflammatory and antioxidative capabilities. Numerous studies have indicated their broad spectrum of pharmacological properties and correlations between their increased supply in the human diet and lower prevalence of various disorders. The positive effects of polyphenols application are mostly discussed in terms of cardiovascular system well-being. However, in recent years, they have also increasingly mentioned as prophylactic and therapeutic factors in the context of neurological diseases, being able to suppress the progression of such disorders and soothe accompanying symptoms. Among over 8000 various compounds, that have been identified, the most widely examined comprise resveratrol, curcumin, luteolin and quercetin. This review focuses on in vitro assessments, animal models and clinical trials, reflecting the most actual state of knowledge, of mentioned polyphenols' medicinal capabilities in epilepsy, demyelinating and neurodegenerative diseases of the central nervous system.

Keywords: curcumin; demyelinating diseases; epilepsy; luteolin; neurodegenerative diseases; polyphenols; quercetin; resveratrol.

Figure 1

Resveratrol’s protective role in demyelination. Resveratrol has been found to modulate the secretory activity of astrocytes and microglial activation by downregulating the release of IL-1β, IL-6, TNF-α, CRP, NO, IL-12, and IL-23, which in turn provides myelin protection and decreases inflammation. Activation of the SIRT1 pathway by resveratrol supports remyelination, protects against oxidative stress and suppresses inflammation. Resveratrol increases the expression of tight junction proteins (such as zonula occludens, occludin and claudin-5) in brain endothelial cells, enhancing blood–brain barrier (BBB) integrity and reducing leukocyte recruitment. In the periphery, resveratrol inhibits inflammatory reactions by increasing IL-10 production in leukocytes and inducing FAS-L-dependent apoptosis.

Figure 2

Curcumin’s protective role in demyelination. Curcumin acts in multiple ways: it modulates the activation state and secretory activity of microglia, promotes remyelination by supporting the maturation of oligodendrocytes from oligodendrocyte progenitor cells (OPCs) and neuronal stem cells (NSCs), and exhibits anti-inflammatory action by downregulating the release of pro-inflammatory cytokines from glial and immune cells (such as IL-17A and pro-inflammatory cytokines TNF-α, IL-2 and IL-6). It also promotes Treg differentiation, controls leukocyte proliferation and regulates Th17 differentiation. Furthermore, curcumin decreases neuroinflammation by enhancing blood–brain barrier integrity and modulating glial activation (by decreasing MMP-9 activity) and immune cell recruitment from the periphery.

Figure 3

Luteolin’s protective role in demyelination. Luteolin decreases SAA release from oligodendrocytes and inhibits microglial activation. It regulates macrophage activation and ROS production, thereby protecting against myelin degradation. Moreover, luteolin supports myelin regeneration by activating oligodendrocyte precursor cells (OPCs) and promoting oligodendrocyte maturation. The anti-inflammatory action of luteolin is associated with decreased expression of cytokines and chemokines, as well as inhibition of NFκB signaling in brain tissue and mononuclear leukocytes in the periphery, limiting their recruitment to the brain and the autoimmune response.

Figure 4

Quercetin’s protective role in demyelination. Quercetin can prevent LPS-driven microglial activation, which leads to neurotoxicity. It supports myelin renewal by activating oligodendrocyte precursor cells (OPCs) and promoting oligodendrocyte maturation. Furthermore, quercetin downregulates the secretion of pro-inflammatory proteins and MMP-9 in brain tissue, reducing inflammation and supporting blood–brain barrier (BBB) integrity. Additionally, in the periphery, quercetin can modulate T cell responses to autoantigens by promoting cell proliferation and inhibiting Th1 cell responses.

Figure 5

Role of Resveratrol in Alzheimer’s disease. Resveratrol prevents amyloid and tau aggregation in the brain and inhibits neuronal apoptosis through SIRT1 activation while minimizing oxidative stress. Additionally, resveratrol may decrease the inflammatory response in leukocytes and inhibit microglial neurotoxicity.

Figure 6

Role of Resveratrol in Parkinson’s disease. Resveratrol may minimize the clinical signs of dopaminergic neuron loss by improving monoamine transport to presynaptic vesicles (elevated VMAT2 levels) and facilitating dopamine exocytotic release. Resveratrol prolongs the presence of dopamine in the synaptic cleft by downregulating DAT and reducing dopamine reuptake. Additionally, resveratrol may decrease α-synuclein aggregation in neurons, thereby preventing neuronal loss.

Figure 7

Curcumin’s action in Alzheimer’s disease. Curcumin decreases oxidative stress in immune cells, prevents amyloid β aggregation, and supports aggregate clearance. In neurons, curcumin elevates DHA synthesis, prevents tau aggregation and hyperphosphorylation, stimulates synaptogenesis, and improves synaptic function. Moreover, curcumin activates the differentiation of neuronal stem cells into new neurons, supporting cognitive functions.

Figure 8

Curcumin’s action in Parkinson’s disease. Curcumin decreases α-synuclein aggregation in neurons and stimulates Trk/PI3K-dependent BDNF synthesis in neurons and glial cells, which in turn increases neuronal survival and restoration. Curcumin prevents the loss of dopaminergic neurons in the substantia nigra by decreasing neuroinflammation and inhibiting the activation of neurotoxic astrocytes.

Figure 9

Reported actions of luteolin on Alzheimer’s disease. Luteolin may reduce the activation of glial cells by decreasing p-JNK and p38 phosphorylation as well as NFκB activity. In neurons, luteolin increases glucose uptake and metabolism and decreases Aβ aggregation. Luteolin has also been shown to enhance cholinergic transmission by regulating cholinesterase activity.

Figure 10

Luteolin’s activity in Parkinson’s disease. Luteolin has been shown to inhibit STAT3 signaling by interfering with its phosphorylation and promoting ubiquitin-dependent degradation. Additionally, luteolin may prevent neuronal apoptosis by downregulating p53, increasing AKT phosphorylation and regulating ROS formation.

Figure 11

Role of Quercetin in Alzheimer’s disease. Quercetin inhibits APP cleavage by BACE1 and prevents Aβ aggregation into toxic oligomers. It also promotes the proteasomal degradation of Aβ40/42. Additionally, quercetin improves mitochondrial function, cholinergic transmission and synaptic plasticity. Quercetin can decrease neuroinflammation by downregulating the release of inflammatory cytokines from immune cells.

Figure 12

Quercetin’s role in Parkinson’s disease. Quercetin improves the function of dopaminergic neurons by promoting mitochondrial biogenesis and enhancing neuronal viability. It also increases the release of dopaminergic neurotransmitters.