From:  Natural compounds targeting glial activation in Alzheimer’s disease: a review of curcumin, resveratrol, and luteolin

 Studies that prove that luteolin has the potential to overcome neuroinflammation.

Researcher and yearModelLuteolin dosage and durationParameterKey resultsConclusion
Che et al., 2020 [41]In vitro: murine astrocyte cell line (C8-D1A), activated with LPS

  • Apigenin & luteolin: 30 μM and 60 μM (pretreatment 1 hour before LPS)

  • Evaluation at 30 minutes, 3 hours, 12 hours, and 24 hours depending on the assay

1. Cell viability
2. Astrocyte activation
3. IL-31 & IL-33 mRNA expression
4. IL-31 & IL-33 protein expression
5. IL-31 & IL-33 secretion
6. Phosphorylation of mitogen-activated protein kinase (MAPK), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), STAT3
7. Translocation & DNA-binding of NF-κB/STAT3
8. Effects of pharmacological inhibitors on signaling pathways		1. Apigenin safe ≤ 60 μM, luteolin safe ≤ 100 μM
2. Apigenin → suppresses ERK, NF-κB, STAT3; more effectively suppresses IL-33
3. Luteolin → suppresses ERK, JNK, p38, NF-κB, STAT3; more effectively suppresses IL-31
4. Both decrease IL-31 & IL-33 secretion, inhibit NF-κB/STAT3 translocation to the nucleus, and decrease DNA-binding activity. Both decrease IL-31 & IL-33 secretion, inhibit NF-κB/STAT3 translocation to the nucleus, and decrease DNA-binding activity		Apigenin and luteolin inhibited LPS-induced astrocyte activation and decreased IL-31 & IL-33 production through modulating MAPK, NF-κB, and STAT3 pathways. Both have potential as neuroprotective agents.
Ma et al., 2025 [29]In vitro: primary cultures of neurons, astrocytes, microglia, as well as mixed cultures of neuron-glia from rat brain

  • CdCl2 as an inducer of neurotoxicity

  • Luteolin: 5–20 μM (pre-treatment)

  • Treatment duration varies according to test (24–48 hours)

1. Neuron viability (survival assay)
2. Neuron morphology (branching, cell body size)
3. Glia markers: glial fibrillary acidic protein (GFAP) (astrocytes), Iba1 (microglia)
4. Proinflammatory cytokines: tumor necrosis factor-alpha (TNF-α), IL-1β, IL-6
5. Neuronal apoptosis: active caspase-3		1. Luteolin increases neuron survival and maintains healthy morphology
2. Luteolin decreases GFAP expression and suppresses Iba1 expression
3. Luteolin decreases the levels of proinflammatory cytokines
4. Luteolin decreases caspase-3 expression
5. Luteolin maintains neuronal survival		Luteolin reduces Cd neurotoxicity by suppressing glial inflammation and protecting neurons from apoptosis, thus supporting neuronal survival. Potential as a neuroprotective agent.
Facchinetti et al. 2022 [76]In vitro: co-culture primary astrocytes & oligodendrocyte precursor cells (OPCs) from the brains of Sprague-Dawley rat pupsCo-Ultramicronized Palmitoylethanola-mide/Luteolin (Co-ultra PEALut) PEA: Luteolin = 10:1; 3 µM; 48 hours1. Viability of astrocytes & OPCs (neutral red assay)
2. Protein & mRNA expression of astrocytes: GFAP, calcium-binding protein B (S100B), glutamine synthetase (GS), HMGB1, IL-6, IL-1β, NF-κB, FGF-2, TGF-β (WB, RT-qPCR)
3. Maturation of OPCs (MBP+/Olig2+ ratio)
4. Oligodendrocyte morphology (surface area, branching/Sholl analysis)		1. Co-ultra PEALut keeps viability normal
2. Co-ultra PEALut suppresses the increase of astrocyte reactivity markers; decreases the expression of proinflammatory cytokines; prevents the decrease of FGF-2, a PPAR-α-independent effect
3. Co-ultra PEALut normalizes MBP+/Olig2+ ratio
4. Co-ultra PEALut prevents cell shrinking & reduced branching		Co-ultra PEALut (PEA + luteolin) normalizes astrocyte-oligodendrocyte communication through anti-inflammatory, pro-trophic, and protective mechanisms. Part of the effect is PPAR-α mediated.
Zhang et al. 2017 [31]In vitro: human brain microvascular endothelial cells (hBMECs) as a blood-brain barrier (BBB) modelLuteolin: 10 µM, pre-treatment before fAβ1–401. Cell viability (MTT assay)
2. Proinflammatory cytokines (IL-1β, IL-6, TNF-α)
3. Adhesion molecules (ICAM-1, VCAM-1)
4. Activation of NF-κB (p65 nuclear translocation)
5. Activation of p38 MAPK (phosphorylation)		1. fAβ1–40 did not decrease cell viability, but increased secretion of IL-1β, IL-6, TNF-α, and expression of ICAM-1 and VCAM-1
2. fAβ1–40 activated p38 MAPK and NF-κB
3. Luteolin decreases cytokines and adhesion molecules, inhibits p38 MAPK phosphorylation, and prevents NF-κB p65 translocation to the nucleus
4. The effects of luteolin are similar to those of a p38 MAPK inhibitor		Luteolin inhibits fAβ1–40-triggered inflammation at the BBB by suppressing the p38 MAPK-NF-κB pathway, thereby decreasing proinflammatory cytokines and adhesion molecules.
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