Targeting neuroimmune interactions: the therapeutic potential of kaempferol in immune-related central nervous system disorders

Medicinal Plants and Bioactive Phytochemicals Targeting Neuroinflammation: Molecular Mechanisms, Preclinical Evidence and Translational Challenges

Neuroinflammation is the inflammatory response within the central nervous system which is linked to many neurological disoders. These disorders include Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, ischemic stroke, among others. Short-term reaction to inflammation within the central nervous system has a contribution to the balance of neural homeostasis and protection of tissues but once the neuroinflammation is persistent, it may lead to the production of inflammatory mediators in excess, oxidative stress, and gradual neuronal damage. Increasing evidence suggests that persistent triggering of microglia and astrocytes, and also the disruption of signaling cascades like nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and NLRP3 inflammasome pathways, plays major role in the progression of neurodegenerative diseases. A lot of attention has been given to medicinal plants as a therapeutic agent that has prospects due to their wide range of phytochemicals and multi-target pharmacological effects. Many plant-based compounds such as curcumin, epigallocatechin-3-gallate, ginsenosides, withanolides, and bacosides have shown properties of anti-neuroinflammation and neuroprotection by inhibiting inflammatory signaling pathways, reducing microglial activation, reduction of oxidative stress, and increasing support for neuron survival. This review gives an in-depth review of medicinal plants with anti-neuroinflammatory properties, focusing on their bioactive compounds, mode of action, and clinical applications in neurological disorders. The current challenges, limitations and future research viewpoint relating to the clinical application of medicinal plant compounds are discussed. The findings show that medicinal plants are potential treatment options for neuroinflammatory disorders.

Recent Updates on the Neuroprotective Effects of Nobiletin in Neurological Disorders: From Molecular Targets to Clinical Prospects.

BACKGROUND Neurological disorders are a significant and increasing public health concern due to their multifactorial pathogenesis, progressive clinical course, and limited long-term effectiveness of current therapeutic strategies. Recent experimental and clinical studies have increasingly focused on bioactive natural compounds as potential modulators of neuroinflammation, oxidative stress and neuronal apoptosis - processes that play a central role in neurodegeneration. Of these, nobiletin (a polymethoxylated flavonoid found in citrus peels) has attracted particular attention thanks to its reported antioxidant, anti-inflammatory and neuroprotective properties in preclinical models. OBJECTIVE We discuss the potential therapeutic role of nobiletin in neurological diseases, examining the relevant molecular mechanisms, preclinical findings, and emerging clinical data. METHODS We searched the electronic databases PubMed, Scopus, and Embase to identify studies examining the therapeutic effects of nobiletin on neurological disorders published up to October 2025. RESULTS This review discusses the neuroprotective actions of nobiletin, with particular attention to its anti-inflammatory, anti-apoptotic, and antioxidant activities and their involvement in major intracellular signaling pathways. In addition, available preclinical findings and emerging clinical data are examined to assess the therapeutic relevance of nobiletin in experimental and clinical models of neurological disorders. DISCUSSION Experimental evidence suggests that nobiletin has neuroprotective properties that could reduce pathological processes associated with neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. However, further well-designed studies are needed to clarify its mechanisms of action and determine whether these effects are beneficial in clinical practice, either as a standalone therapy or in combination with existing treatments. CONCLUSION Overall, the available evidence indicates that nobiletin may have beneficial effects on a wide range of neurological conditions, such as Parkinson's disease, Alzheimer's disease, stroke, epilepsy, depression, schizophrenia, multiple sclerosis, glioma, and sciatic nerve injury.

Therapeutic potential of apigenin in neurodegenerative diseases and brain health

Apigenin as a Potential Modulator of Neuroinflammation in Multiple Sclerosis: A Review

Simple Summary Multiple sclerosis is an autoimmune disease in which the immune system mistakenly attacks the myelin of neurons in the brain and spinal cord, causing chronic inflammation, damage, and disability. Current treatments target the immune system but often bring side effects and fail to stop the ongoing loss of neurons. Naturally occurring compounds are increasingly studied for their ability to modulate neuroinflammation. This review explores apigenin, a natural compound abundantly found in parsley, chamomile, and citrus fruits, focusing on its anti-inflammatory and neuroprotective properties as a potential adjuvant treatment for multiple sclerosis. The available evidence indicates that apigenin lowers overactive immune cell responses, reduces damaging inflammatory signals, and helps to protect neurons. Despite this consistent mechanistic evidence in various animal models, direct data in humans remain limited to a small number of studies on immune cells taken from patients, and no clinical trials have tested apigenin as a treatment. Further research, including clinical trials, is needed to confirm whether apigenin can help to manage and improve treatment of those affected by the disease.

Alkaloids as Emerging Neuroprotective Agents for Neurodegenerative Disorders: Insights into Tryptanthrin and Its Derivatives

Neurodegenerative conditions are incurable, progressive disorders characterized by the slow and irreversible loss of neurons. This neuronal loss can lead to several neuropsychiatric disorders and long-term complications. Despite significant advances in understanding the mechanisms of neurodegenerative disease, currently, there is no cure for neurodegenerative diseases, highlighting the urgent need for novel neuroprotective strategies. Alkaloids are an important class of bioactive substances that exhibit neuroprotection against several neurodegenerative diseases. Tryptanthrin, an indoloquinazoline alkaloid, shows strong anti-inflammatory, antioxidant, and neuroprotective properties. In this review, we described the pathophysiology of neurodegenerative diseases and summarized several alkaloids’ neuroprotective properties. Furthermore, we showed protective benefits of tryptanthrin and its derivatives against neurodegenerative illnesses, focusing on their modulation of oxidative stress, neuroinflammation, neuronal death, and related signaling pathways in cellular and animal models of neurodegenerative diseases. However, various challenges, such as clinical evidence, pharmacokinetic studies, and long-term treatment effects, are not well documented. Future research on tryptanthrin and its derivatives should focus on the optimization of drug delivery methodologies and clinical studies to establish its potential as a therapeutic candidate for neurodegenerative diseases.

613. The analysis of the impact of non-steroidal drug and the TRP compound on the immune profile of microglia: study in an Alzheimer’s disease model

Abstract Background Neuroinflammation is a hallmark of central nervous system (CNS) disorders and plays a critical role in the progression of neurodegenerative diseases, including Alzheimer’s disease. Microglia, the resident immune cells of the CNS, act as key regulators of inflammatory responses and are rapidly activated in response to pathological stimuli such as amyloid-β accumulation, neuronal injury, and synaptic dysfunction. While acute microglial activation is essential for tissue homeostasis and debris clearance, sustained or dysregulated activation contributes to chronic inflammation and neurodegeneration. Non-steroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, are widely used to attenuate neuroinflammatory processes. Although ibuprofen exhibits anti-inflammatory and neuroprotective properties, achieving therapeutic concentrations in the brain requires prolonged dosing, which exacerbates various peripheral and central side effects. Therefore, there is a critical need to develop novel anti-inflammatory compounds with improved brain bioavailability and safer therapeutic profiles in order to effectively modulate neuroinflammation and in consequently, neurodegeneration. Aims & Objectives We propose as a goal of the present study a comparative evaluation of the anti-inflammatory and pro-resolution potential of ibuprofen (IBU) and a novel compound (TRP) in immune-activated primary microglial cell cultures derived from C57BL/6J (WT) and APPNL-F/NL-F knock-in mice (KI, animal model of AD). Method Primary Microglial cells were prepared from the cortices of 1-2-day-old mouse brains. The cells were treated for 1 h with IBU or TRP (10 μM) and then stimulated for 24 h with bacterial endotoxin (lipopolysaccharide, LPS, 100 ng/mL). We measured the cell death parameters (lactate dehydrogenase, LDH assay), the secretion of nitric oxide (NO) synthesis by Griess reaction, and pro- (IL-1β, IL-6, CCL2) and anti-inflammatory cytokines (IL-10, IL-4) profile release in control and AD-derived microglia cells using ELISA kits. Results Exposure to IBU and TRP significantly reduced LPS-induced microglial cell death, as evidenced by decreased LDH release. Moreover, LPS stimulation led to an upregulation of NO, and IL-1β, IL-6, and IL-10 release as well as CCL-2 production, more evident in microglia cells derived from KI mice. Most of the pro-inflammatory markers released were attenuated by TRP administration. Interestingly, TRP treatment preserved the LPS-induced elevation of IL-10, which may suggest not only an anti-inflammatory but also a pro-resolving profile of TRP action in primary microglia cultures obtained also from the AD model. Discussion & Conclusions Our findings suggest that TRP modulates microglial activation in a varied manner. Its simultaneous ability to influence the proinflammatory and anti-inflammatory profiles of microglial cells in an AD model positions this compound as a promising candidate for further investigation in the context of neuroimmune dysregulation and a tool for pharmacotherapy of resolution. The study was supported by a programme coordinated by the Medical Research Agency, co-financed by the European Union under the NextGeneration EU initiative, within the framework of the National Recovery Plan, Component D, Investment D3.1.1 (project no. 2024/ABM/03/KPO/KPOD.07.07-IW.07-0173/24-00).