Curcumin exhibits significant immunomodulatory effects on macrophages, which are pivotal innate immune cells involved in inflammatory responses and tissue homeostasis. Experimental studies demonstrate that curcumin preferentially suppresses pro-inflammatory M1 macrophage polarization while promoting anti-inflammatory M2 phenotype, primarily by inhibiting the signal transducer and activator of transcription 3 (STAT3) signaling pathway (Ran et al., 2021; Abdollahi et al., 2023; Deswal et al., 2024). At the molecular level, curcumin reduces lipopolysaccharide (LPS)-induced production of TNF-α, IL-6, and nitric oxide in macrophages by downregulating iNOS and COX-2 expression (Wang et al., 2019). In ischemic stroke models, curcumin administration attenuates stroke-induced white matter damage, improves functional outcomes, and reduces microglial pyroptosis, mediated at least partially through the suppression of NF-κB/NLRP3 signaling pathways (Ran et al., 2021). Similarly, in myocardial infarction, curcumin improves cardiac function and reduces post-MI fibrosis by inhibiting macrophage-fibroblast crosstalk during the acute phase and suppressing IL-18-TGF-β1-p-SMAD2/3 signaling in cardiac fibroblasts (Zhao et al., 2021). In addition, it modulates myocardial inflammation through AMPK-regulated M1/M2 macrophage polarization (Yan et al., 2021). Additional evidence indicates that curcumin protects against particulate matter-induced lung injury by suppressing oxidative stress and inflammatory activation in macrophages (Lee et al., 2023). In ulcerative colitis models characterized by dysregulated M1/M2 macrophage ratios and enhanced M1 activation, curcumin treatment normalizes aberrant macrophage activation, inhibits macrophage chemotaxis, and alleviates inflammatory responses (Chen et al., 2023). Collectively, these findings establish macrophages as crucial cellular mediators of the immunomodulatory actions of curcumin, playing a vital role in regulating immune responses and potentially ameliorating macrophage-associated systemic and neuroinflammatory conditions. The compound demonstrates therapeutic potential across multiple disease states by modulating macrophage polarization and function.

Emerging research has elucidated the potent regulatory effects of curcumin on microglia, the resident immune cells of the central nervous system. Under neuroinflammatory conditions, curcumin (5-25 μM) can attenuate LPS-induced microglial activation, achieving approximately 60% reduction in pro-inflammatory cytokine release (TNF-α, IL-1β, IL-6) by suppressing the TLR4/MyD88/NF-κB signaling cascade (Gao et al., 2019; Zhang et al., 2019). The compound exhibits anti-inflammatory and antioxidant properties by inhibiting NOX2-mediated ROS production in activated microglia while upregulating the Nrf2/Heme Oxygenase-1 (HO-1) antioxidant pathway (Duan et al., 2022; Lin et al., 2022; Xu et al., 2025a). In models of traumatic brain injury, curcumin treatment mitigates brain damage, reduces IL-1β and IL-6 levels, promotes microglial polarization toward the M2 phenotype, and downregulates C1ql3 protein expression (Zhang et al., 2023b). Similarly, in subarachnoid hemorrhage, curcumin demonstrates neuroprotective effects by suppressing neuronal ferroptosis through the modulation of Nrf2/HO-1 signaling (Xu et al., 2025b). Notably, curcumin metabolites such as tetrahydrocurcumin retain biological activity in regulating microglial triggering receptor expressed on myeloid cells two signaling, potentially explaining the beneficial effects of the compound despite limited blood-brain barrier permeability (Jiang et al., 2023; Genchi et al., 2024). These findings collectively establish microglia as crucial cellular mediators of the immunomodulatory actions of curcumin, highlighting its therapeutic potential in alleviating microglia-associated neuroinflammatory pathologies through multifaceted mechanisms of action. The ability of the compound to modulate microglial activation states and signaling pathways positions it as a promising candidate for neuroinflammatory intervention.

Curcumin demonstrates significant immunomodulatory capacity in T cell-mediated diseases through pleiotropic mechanisms targeting cellular activation, differentiation, and effector functions. In autoimmune conditions, curcumin (10–25 μM) ameliorates disease severity by suppressing pathogenic Th1/Th17 responses while enhancing the activity of regulatory T cells (Tregs) (Fasihi et al., 2024; Ghoushi et al., 2024; Nosratabadi et al., 2024). Experimental autoimmune encephalomyelitis (EAE) studies reveal that the neuroprotective effects of curcumin are mediated, at least partially, through AMPK/SIRT1 activation, ultimately attenuating EAE-induced neuronal demyelination, oxidative stress, and neuroinflammation (ELBini-Dhouib et al., 2022; Sadek et al., 2024). Rheumatoid arthritis models demonstrate the ability of curcumin to inhibit Th17 differentiation via suppression of STAT3 phosphorylation, with additional evidence showing its regulation of the inc00052/miR-126-5p/PIAS2 axis through the JAK2/STAT3 signaling pathway (Xiao et al., 2022; Kou et al., 2023; Deng et al., 2024). In allergic disorders, curcumin modulates Th1/Th2 balance by downregulating GATA3 expression and reducing IL-4/IL-5 production in ovalbumin-sensitized models (Wang et al., 2022). Therapeutic applications in thyroid cancer reveal that curcumin can enhance anti-tumor immunity in anaplastic thyroid carcinoma by boosting CD8⁺ T-cell function and inactivating the AKT/mTORC1/STAT3/PD-L1 axis (Vaiss et al., 2024). Furthermore, curcumin reduces severity in acute lung injury/acute respiratory distress syndrome and uncontrolled inflammation by promoting naïve CD4⁺ T-cell differentiation into CD4⁺CD25+FOXP3+ Tregs (Chai et al., 2020). In summary, curcumin exhibits broad therapeutic potential across autoimmune diseases, allergic disorders, viral infections, and cancer immunotherapy through its multifaceted immunomodulatory effects on T-cell subsets, highlighting its value as a versatile immunotherapeutic agent (Figure 2).

AD is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and behavioral disturbances and is the most prevalent cause of dementia worldwide (Scheltens et al., 2021; Jucker and Walker, 2023). The neuropathological hallmarks of AD include the accumulation of extracellular amyloid-β (Aβ) plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, which collectively contribute to synaptic dysfunction and neuronal degeneration (Graff-Radford et al., 2021; Serrano-Pozo et al., 2021; Ossenkoppele et al., 2022). Despite extensive research, the precise etiology of AD remains unclear, with proposed involvement of genetic predisposition, environmental factors, and metabolic disturbances. Owing to the growing global aging population and limited availability of disease-modifying therapies, elucidating AD pathogenesis is challenging in contemporary neuroscience research. Given the complex and multifactorial nature of AD pathogenesis, developing effective pharmacological interventions remains a formidable challenge in neurology and drug discovery. Current therapeutic approaches primarily focus on symptomatic management, with acetylcholinesterase inhibitors such as donepezil, rivastigmine, and galantamine enhancing cholinergic neurotransmission to alleviate cognitive deterioration (Se Thoe et al., 2021; Liu et al., 2024a). Furthermore, the N-methyl-D-aspartate receptor antagonist memantine provides partial neuroprotection by modulating glutamatergic excitotoxicity (Vaz and Silvestre, 2020; Pardo-Moreno et al., 2022; Varadharajan et al., 2023). However, these treatments offer merely transient symptomatic stabilization without altering disease progression, thus stimulating increasing interest in natural compounds with multimodal neuroprotective properties. Among these compounds, curcumin, the principal bioactive polyphenol derived from Curcuma longa (turmeric), has emerged as a promising candidate for AD intervention, owing to its diverse pharmacological activities targeting multiple pathological pathways implicated in AD progression.

Curcumin exhibits multiple pharmacological properties relevant to AD pathogenesis, including anti-amyloidogenic, anti-tau, antioxidant, and anti-inflammatory effects (Aggarwal and Harikumar, 2009; Azzini et al., 2024). Recent studies demonstrate that during AD progression, impaired adult neurogenesis in the dentate gyrus can be ameliorated by curcumin treatment through modulation of GSK3β/Wnt/β-catenin and CREB/BDNF pathways via PI3K/Akt regulation, reducing apoptosis and improving neurogenesis in AD mouse models (Lou et al., 2024). In AD transgenic mice, curcumin administration downregulates hippocampal expression of HMGB1, RAGE, TLR4, and NF-κB, improving cognitive function by suppressing the HMGB1-RAGE/TLR4-NF-κB inflammatory signaling cascade (Han et al., 2021). As a dietary supplement, curcumin benefits patients with insulin resistance, type 2 diabetes (T2D), and AD by reducing circulating levels of IAPP and GSK-3β while alleviating insulin resistance-related markers, consequently lowering the risk of T2D and AD (Thota et al., 2020). Notably, prophylactic administration of curcumin prior to Aβ deposition demonstrates preventive potential for AD, possibly through facilitating Aβ₄₂ clearance from the brain to peripheral circulation (Mei et al., 2020). Additionally, curcumin enhances BDNF-ERK signaling to mitigate AD-associated cognitive deficits (Zhang et al., 2015). Emerging evidence reveals that curcumin treatment significantly alters the composition of gut microbiota in AD mice. The compound undergoes biotransformation by gut microbiota through reduction, demethoxylation, demethylation, and hydroxylation, yielding neuroprotective metabolites (Sun et al., 2020; Leblhuber et al., 2021). These findings suggest a gut-liver-brain axis mediating metabolic and cognitive functions, possibly by reducing fatty acid synthesis, altering cholesterol metabolism, inhibiting hepatic lipogenesis-related pathways, and modulating synaptic plasticity-related pathways in the brain, ultimately suppressing weight gain and improving behavioral and cognitive functions (Pluta et al., 2022; Lamichhane et al., 2024).

The therapeutic efficacy of curcumin in AD is considerably constrained by its limited ability to cross the blood-brain barrier. To address this limitation, researchers have explored combination therapy with ginkgo biloba extract and curcumin, demonstrating the suppression of acetylcholinesterase, caspase-3, hippocampal amyloid-β (Aβ1-42), and phosphorylated tau levels and reduced expression of pro-inflammatory cytokines TNF-α and IL-1β in rat models. This combined treatment also significantly decreased malondialdehyde and modulated reduced glutathione levels (Assi et al., 2023). To enhance the neuroprotective effects of curcumin in AD, advanced delivery systems have been developed. Notably, carrier-free curcumin nanoparticles (CNPs) formed through molecular self-assembly exhibit multivalent binding to Aβ, resulting in superior inhibition of Aβ aggregation. Following intranasal administration, these lipid-based formulations release CNPs and cardiolipin in response to the oxidative microenvironment characteristic of AD. The CNPs modulate microglial polarization (M1→M2) via TLR4/NF-κB pathway inhibition, while simultaneously suppressing Aβ aggregation and enhancing microglial phagocytic clearance of Aβ, thereby overcoming barriers to microglial repolarization (Feng et al., 2024). Intravenous administration of novel brain-targeted nanoparticles (Ce/Zr-MOF@Cur-Lf) facilitates rapid brain entry and ameliorates multiple AD pathological features, including neuronal damage, Aβ deposition, cholinergic system dysfunction, oxidative stress, and neuroinflammation (Yang et al., 2024c). Furthermore, localized delivery of curcumin using human hair keratin/chitosan (C/K) hydrogels may enhance neural regeneration and repair nerve damage, representing an innovative approach for targeted therapy.

Collectively, the existing preclinical evidence from in vitro and in vivo studies substantiates the neuroprotective efficacy of curcumin in AD pathogenesis, primarily mediated through its anti-neuroinflammatory properties and cognitive-enhancing effects. Nevertheless, substantial research efforts are still warranted to bridge the gap between these promising experimental findings and clinical applications, particularly concerning bioavailability optimization and therapeutic regimen standardization (Sun et al., 2024).

PD is a progressive neurodegenerative disorder pathologically characterized by selective degeneration of dopaminergic neurons in the substantia nigra pars compacta and the presence of intraneuronal proteinaceous inclusions known as Lewy bodies, predominantly composed of α-synuclein aggregates (Kalia and Lang, 2015; Bloem et al., 2021). Clinically, PD manifests with cardinal motor symptoms including bradykinesia, resting tremor, rigidity, and postural instability, accompanied by various non-motor features such as cognitive impairment, sleep disturbances, and autonomic dysfunction (Hayes, 2019; Morris et al., 2024). With a global prevalence exceeding six million cases, PD ranks as the second most common neurodegenerative disorder after AD, imposing substantial socioeconomic burdens (Ascherio and Schwarzschild, 2016; Weintraub et al., 2022). The etiology of PD remains multifactorial, involving complex interactions between genetic predisposition, environmental exposures, and aging-related cellular dysfunction (Lotankar et al., 2017; Tysnes and Storstein, 2017). Mutations in genes encoding α-synuclein, leucine-rich repeat kinase 2, and PARKIN have provided crucial insights into pathogenic mechanisms, including mitochondrial dysfunction, proteostasis failure, and neuroinflammation (Jankovic and Tan, 2020; Brooker and Gonzalez-Latapi, 2025; Xiao et al., 2025). Current therapeutic approaches primarily focus on dopamine replacement using levodopa, which provides symptomatic relief but fails to halt disease progression. Emerging disease-modifying strategies targeting α-synuclein pathology or employing gene-based interventions show promise but require further validation (Du et al., 2020; Chen et al., 2022). Curcumin, a natural polyphenol, demonstrates significant potential in PD and other neurodegenerative conditions. Experimental evidence indicates that curcumin exerts neuroprotective effects by modulating the BDNF/PI3k/Akt signaling pathway, which plays a critical role in neuroregeneration and anti-apoptotic processes (Jin et al., 2022). Furthermore, curcumin prevents rotenone-induced PD in murine models by inhibiting microglial NLRP3 inflammasome activation and mitigating mitochondrial dysfunction (Xu et al., 2023). In rotenone-exposed mice, curcumin administration activates the p62-Keap1-Nrf2 pathway, enhances autophagy, and improves antioxidant capacity (Rathore et al., 2023). Additional mechanisms include neuroprotection through HDAC6-NLRP3 pathway modulation and amelioration of MPTP-induced gastrointestinal dysfunction, gut microbiota dysbiosis, and short-chain fatty acid profile alterations (Cai et al., 2025). To enhance therapeutic efficacy, advanced delivery systems have been developed, including mitochondria-targeting biomimetic nanoparticles functionalized with curcumin (Zhu et al., 2022; Cai et al., 2023). These nanoparticles localize to damaged neuronal mitochondria in inflammatory environments and modulate the NAD+/SIRT1/PGC-1α/PPARγ/NRF1/TFAM signaling cascade, alleviating MPP + -induced neuronal toxicity and mitochondrial dysfunction (Zheng et al., 2023). Moreover, curcumin-loaded nanoemulsions have demonstrated superior efficacy in preventing motor deficits and inhibiting complex I dysfunction, representing promising nanomedicine applications for PD (Ramires Junior et al., 2021). While preclinical studies consistently demonstrate the ability of curcumin to mitigate PD symptoms and attenuate neuroinflammation in vivo, rigorous clinical trials remain necessary to substantiate its therapeutic potential for patients with PD and establish optimal treatment protocols.

MS is a chronic autoimmune-mediated demyelinating disease of the central nervous system, characterized by multifocal inflammatory lesions, axonal damage, and progressive neurological dysfunction (Kuhlmann et al., 2023). As the most prevalent non-traumatic cause of neurological impairment in young adults, MS affects approximately 2.8 million individuals worldwide, with a higher prevalence among females and in temperate geographical regions. The clinical manifestations of MS exhibit significant heterogeneity, ranging from relapsing-remitting episodes to progressive neurological decline, reflecting a complex interplay between genetic susceptibility and environmental triggers (Travers et al., 2022). The pathogenesis of MS involves the infiltration of autoreactive T cells across the blood-brain barrier, initiating an inflammatory cascade targeting myelin, followed by oligodendrocyte loss and impaired axonal conduction (Perez et al., 2023). Although the precise etiology remains elusive, genome-wide association studies have identified over 200 risk loci, particularly within the major histocompatibility complex region, underscoring the importance of immune dysregulation (Hauser and Cree, 2020). Current therapeutic options for the disease, such as anti-CD20 monoclonal antibodies and sphingosine-1-phosphate receptor modulators, demonstrate limited efficacy in progressive forms of MS (de Seze et al., 2023; Klotz et al., 2023). Th17 cells are critical immune participants in the pathophysiology of MS (Qureshi et al., 2018). Curcumin inhibits the proliferation of Th17 cells and reduces the production of pro-inflammatory cytokines, including TNF-α, IL-22, and IL-17, offering therapeutic potential for MS (Ghoushi et al., 2024). In addition, curcumin exerts neuroprotective effects by downregulating AXL-mediated astrocyte-driven inflammation in cuprizone-induced mouse models, targeting MS treatment (Zhang et al., 2025). In EAE mouse models and LPS-stimulated BV-2 microglial cells, curcumin may ameliorate microglial-mediated inflammatory responses by inhibiting the AXL/JAK2/STAT3 signaling pathway (Sun et al., 2022). Reports indicate that curcumin and its semi-synthetic derivative F-curcumin suppress the expression of IL-1β, IL-4, IL-10, IL-17, interferon-γ, and TGF-β during EAE induction, mitigating MS-associated inflammation (Khosropour et al., 2023). To enhance the bioavailability of curcumin in the treatment of MS, researchers have designed a prodrug, curcumin monoglucuronide, which, when administered intravenously or intraperitoneally, alters the overall gut microbiome composition and modifies the abundance of specific bacterial populations to suppress neuroinflammation and improve MS outcomes (Khadka et al., 2021). In materials science, investigators have utilized high-density lipoprotein-mimicking peptide-phospholipid scaffolds (HPPS) as carriers to improve the bioavailability of curcumin, effectively reducing inflammatory monocyte infiltration across the blood-brain barrier, inhibiting microglial proliferation, and limiting the infiltration of other effector immune cells, thereby decreasing the incidence of EAE in mice (Lu et al., 2020). Similarly, polymeric forms of nano-curcumin correct the balance of pro-inflammatory and anti-inflammatory gene expression in EAE models, reduce oxidative stress, enhance myelin regeneration, and increase progenitor cell markers (Mohajeri et al., 2015).

In summary, curcumin demonstrates the potential to inhibit neuroinflammation in EAE models, improving outcomes in MS.

Stroke represents a significant global health burden, ranking as the second leading cause of death and the third leading cause of disability worldwide. This cerebrovascular event occurs when arterial occlusion or vessel rupture interrupts blood flow to the brain, resulting in the rapid onset of neurological deficits (Kong et al., 2022; Hilkens et al., 2024). The pathophysiological cascade involves excitotoxicity, oxidative stress, and neuroinflammation, ultimately leading to neuronal death within minutes to hours following ischemic injury (Feigin et al., 2025). Recent advancements in the management of acute stroke, particularly the expansion of thrombolytic time windows and the widespread adoption of endovascular thrombectomy, have fundamentally altered the treatment landscape for ischemic stroke (Bushnell et al., 2024). However, significant challenges persist, including narrow therapeutic time windows, the risk of hemorrhagic transformation, and limited neuroprotective strategies (Caso et al., 2024). Moreover, recovery post-stroke remains suboptimal for many patients, with approximately 50% of survivors experiencing long-term disabilities. Therefore, identifying more effective therapeutic targets is critical for enhancing stroke rehabilitation (Kong et al., 2024a; Wegener et al., 2024). Research indicates that curcumin partially mitigates stroke-induced white matter injury and improves neurological function by inhibiting the NF-κB/NLRP3 signaling pathway, providing neuroprotection following a stroke (Ran et al., 2021). Furthermore, curcumin pretreatment enhances ischemic stroke outcomes by preserving blood-brain barrier integrity, promoting synaptic remodeling, and downregulating the phosphorylation of NF-κB and MMP-9, thereby suppressing inflammatory responses (Wu et al., 2021). In models of intracerebral hemorrhage (ICH), curcumin treatment facilitates the inhibition of oxidative stress in microglia by activating the Nrf2/HO-1 pathway and promoting neurological recovery post-ICH, thereby alleviating neuronal damage (Duan et al., 2022). To enhance the therapeutic efficacy of curcumin in stroke, a combined therapy utilizing curcumin and human umbilical cord-derived mesenchymal stem cells exerts anti-inflammatory and antioxidant effects through the AKT/GSK-3β/β-TrCP/Nrf2 axis, improving neurological function following acute ischemic stroke (Li et al., 2023). Similarly, in materials science, researchers have encapsulated curcumin in mPEG-PCL nanoparticles, which are administered intranasally to deliver curcumin directly to the brain. This approach reprograms pro-inflammatory microglia to an anti-inflammatory phenotype, reducing neuronal inflammatory death and hematoma volume in mouse models of ICH (Duan et al., 2024). Additionally, encapsulating curcumin in polymer-based nanoparticles has shown superior therapeutic effects compared with curcumin alone in inhibiting erastin-induced ferroptosis in HT22 hippocampal cells (Yang et al., 2021a).

In summary, curcumin exhibits neuroprotective properties in ischemic and hemorrhagic stroke models by inhibiting neuroinflammation and mitigating neuronal damage, thereby promoting recovery from stroke.

ALS is a devastating neurodegenerative disorder characterized by the progressive degeneration of upper and lower motor neurons, leading to muscle weakness, paralysis, and ultimately respiratory failure within 3–5 years of symptom onset (Feldman et al., 2022). The global prevalence of ALS is approximately 4–6 cases per 100,000 individuals, making it the most common motor neuron disease among adults and imposing significant physiological and psychological burdens on patients and caregivers (Goutman et al., 2022; Akcimen et al., 2023). The pathogenesis of ALS involves a complex interplay between genetic susceptibility, particularly mutations in C9ORF72, superoxide dismutase 1 (SOD1), TARDBP, and fused in sarcoma (FUS), and environmental factors, resulting in multiple pathological mechanisms, including protein misfolding, oxidative stress, mitochondrial dysfunction, and neuroinflammation. Despite extensive research efforts, current therapeutic options remain limited (Goutman et al., 2022; Ilieva et al., 2023).

Recent studies have identified solid lipid curcumin particles as a potential estrogen replacement therapy that may mitigate the progression and pathogenesis of TDP-43-related diseases (Majumder et al., 2025). In addition, curcumin treatment enhances ATP levels by attenuating the sequestration of pyruvate kinase mediated by FUS aggregation, thereby offering a promising avenue for ALS treatment (Shi et al., 2023). Furthermore, researchers have discovered a novel potent polyphenolic compound, ethoxycurcumin, an effective inhibitor in reducing the risk of fatal ALS by preventing the abnormal misfolding and aggregation of SOD1 into amyloid aggregates (Kouhi et al., 2024). This mechanism may be due to the stronger binding affinity of curcumin to SOD1 protofibrils, facilitated by greater van der Waals interactions (Sharma et al., 2023). Collectively, these findings indicate that curcumin significantly inhibits ALS symptoms in vitro and in vivo, providing new therapeutic directions for improving the prognosis of ALS.

Epilepsy is a chronic neurological disorder characterized by recurrent, unprovoked seizures resulting from abnormal, synchronous neuronal activity in the brain. It is among the most prevalent neurological conditions, significantly impacting morbidity, mortality, and quality of life (Specchio et al., 2022). Seizures can manifest in various clinical phenotypes, ranging from brief focal awareness seizures to generalized convulsive events, reflecting underlying network dysfunction (Deng and Husari, 2024; Krishnamurthy, 2025). The mechanisms underlying epilepsy include ion channel dysfunction (such as SCN1A mutations in Dravet syndrome), heightened excitability of glutamatergic pathways, and impaired GABAergic inhibition. Despite the availability of antiepileptic drugs, approximately 30% of patients experience drug-resistant epilepsy, necessitating alternative interventions such as surgical resection, neurostimulation, or dietary therapies. Consequently, novel therapeutic approaches are essential (Kanner et al., 2024; Pellinen et al., 2024). Recent studies have demonstrated that curcumin can significantly reduce the frequency of seizures in the clinical treatment of pediatric refractory epilepsy (Erfani et al., 2022). In rat models of epilepsy, curcumin administration markedly decreased seizure-like activity, with reduced mRNA and protein levels of Na+, thereby diminishing seizure occurrences (Kumar et al., 2019). In a pentylenetetrazol (PTZ)-induced seizure model, curcumin exerted anticonvulsant effects by elevating serotonin levels in the brain, influencing receptors such as 5-HT1A, 5-HT2C, and 5-HT4, and potentially by downregulating 5-HT7 gene expression (Arbabi Jahan et al., 2018). Moreover, curcumin attenuates glial cell activation and ameliorates cognitive deficits in patients with chronic epilepsy (Kaur et al., 2015). In a lithium-pilocarpine rat model inducing status epilepticus, positron emission tomography revealed that curcumin treatment inhibited cerebral glucose metabolism, reduced body weight, mitigated hippocampal neuronal damage, and decreased neuroinflammation, ultimately reducing seizure frequency (Slowing et al., 2023). Furthermore, in the same model, curcumin conferred neuroprotection by inducing autophagy and inhibiting necroptotic apoptosis, safeguarding hippocampal neurons from status epilepticus-induced injury (Wang et al., 2017). To enhance the anticonvulsant properties of curcumin and improve its bioavailability, researchers have micronized the compound using supercritical carbon dioxide processing. In adult zebrafish models of PTZ-induced seizures, micronized curcumin exhibited effects comparable to those of classical antiepileptic drugs (Bertoncello et al., 2018).

In summary, curcumin demonstrates potential as an antiepileptic agent in various models by suppressing neuroinflammation, thereby reducing seizure frequency (Figure 3).