NEUROTHERAPEUTIC POTENTIAL OF CUSCUTA REFLEXA (AMARBAEL): A MULTI-TARGETED HERBAL MODULATOR OF THE P2X7–NLRP3 INFLAMMASOME AXIS IN ALZHEIMER’S DISEASE

Repurposing apremilast for alzheimer’s disease: multitarget modulation of cAMP‑PI3K/Akt–GSK‑3β and NF‑κB signaling

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

Neuroinflammation is recognized as a pivotal pathological process underlying a spectrum of neurological disorders. The exploration of natural flavonoids as therapeutic agents has substantially advanced our understanding of strategies to mitigate neuroinflammatory injury. Accumulating evidence indicates that kaempferol—a dietary flavonoid abundantly present in various fruits and vegetables—exerts potent neuroprotective effects in multiple neurological conditions. Its beneficial actions are mediated through multi-target mechanisms, primarily involving the suppression of microglial activation, modulation of immune cell reactivity, and enhancement of endogenous antioxidant defenses. These mechanisms collectively contribute to reduced production of inflammatory mediators, alleviation of oxidative stress, and inhibition of neuronal apoptosis, thereby counteracting the pathogenesis of various neuroinflammatory diseases. This review summarizes current knowledge on the protective role of kaempferol in the pathogenesis and progression of central nervous system disorders. We further elucidate the underlying molecular and cellular mechanisms, as well as autophagy and oxidative stress. Additionally, potential challenges in clinical translation, such as bioavailability and blood-brain barrier permeability, are discussed to guide future research in this promising field. Elucidating the pleiotropic actions of kaempferol will not only deepen our understanding of its pharmacodynamics but may also open new avenues for the prevention and treatment of neuroinflammatory-related neurological diseases.

Ferula assafoetida as a Multi-Target Therapeutic Candidate for Parkinson's Disease: A Narrative Review

Parkinson’s disease (PD) presents a complex challenge in neurodegenerative research due to the persistent lack of disease-modifying therapies, prompting exploration of natural compounds with multi-target capabilities to modulate multiple pathways. Hence, this review evaluates the therapeutic potential of the ayurvedic plant, Ferula assafoetida, as a candidate for PD treatment. The phytochemical profile of F. assafoetida, rich in bioactive sulfur volatiles, phenolic acids, coumarins, and terpenes, aligns with mechanisms implicated in PD pathogenesis, including oxidative stress, inflammation, and mitochondrial dysfunction. Critically, recent activity-guided isolation studies have successfully identified specific sesquiterpene coumarins, such as karatavicinol and farnesiferol C, as potent monoamine oxidase-B (MAO-B) inhibitors, demonstrating efficacy in ameliorating motor deficits and protecting dopaminergic neurons in a murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. This breakthrough provides the first direct experimental evidence for F. assafoetida in a PD model, transitioning its status from a traditional remedy to a source of validated, bioactive lead compounds. While mammalian models offer crucial translational validation, zebrafish, with their conserved dopaminergic pathways, genetic tractability, and suitability for high-throughput screening, emerge as an ideal complementary platform for accelerating future research. Advanced phytochemical profiling, integrating chromatographic methods and in silico molecular docking, could prioritize lead compounds for further investigation. The integration of gene expression analysis in zebrafish models, alongside behavioral assays, enables a comprehensive understanding of the impact of this plant on PD-related pathways. This pertinent evidence now positions F. assafoetida as a viable preclinical candidate. Future research should prioritize chemical standardization across different plant sources and in vivo mechanistic studies in zebrafish. By illustrating the synergy between phytochemistry and innovative model systems, this review lays the groundwork for exploring F. assafoetida as a promising candidate for novel PD therapies and related neurodegenerative disorders.

INHIBITION OF P2X7R-DRIVEN NLRP3 INFLAMMASOME ACTIVATION BY Dalbergia sissoo IN EXPERIMENTAL ALZHEIMER’S DISEASE

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder presenting memory loss, cognitive decline, synaptic dysfunction and irreparable neuronal damage. It is the most common dementia disorder in the world, and a major public health problem. Although much research has been done into this, no pharmacologic treatments yet exist that can effectively prevent or reverse disease progression and only offer symptomatic relief. The purinergic P2X7 receptor and the subsequent NLRP3 inflammasome signaling pathway have well established as key players in the regulation of neuro-inflammatory responses in AD. Extracellular ATP binding to the P2X7 receptor leads to assembly of the NLRP3 inflammasome complex. Caspase-1 activation and further increase in the production of pro-inflammatory cytokines like interleukin-1 beta (IL-1β) and interleukin-18 (IL-18), speed up the injury of neurons and disease progression. As a natural alternative remedy, medicinal plants with multi-target pharmacological activities have been an object of special interest for the treatment of AD. Dalbergia sissoo Roxb. Sheesham is a common medicinal tree of the Fabaceae family that has been traditionally utilized for inflammatory, neurological and oxidative stress disorders. Plant have shown the presence of various bioactive compounds such as flavonoids and phenolic compounds, with notable antioxidant, anti-inflammatory and neuroprotective effects. The therapeutic properties of Dalbergia sissoo can be linked to its anti-oxidative properties, down-regulation of pro-inflammatory cytokines and protection of neuronal cells from inflammatory damage. Recently increases of its phytochemical ingredients may affect ATP-mediated activation of P2X7 receptor and inhibition of NLRP3 inflammasome signalling in Alzheimer’s disease. The present review aims to delve into the potential mechanism of action of Dalbergia sissoo in Alzheimer’s disease (AD), focusing on the interaction between the P2X7 receptor and NLRP3 inflammasome.

TARGETING ALZHEIMER’S DISEASE WITH CARNOSIC ACID: THERAPEUTIC MODULATION OF THE P2X7 RECEPTOR–NLRP3 INFLAMMASOME PATHWAY IN RAT MODELS

Alzheimer disease is a progressive neurodegenerative disorder which illustrates cognitive loss, synaptic dysfunction and neuronal loss. There are emerging accumulating evidences that chronic neuroinflammation is at the center of the pathogenesis of the disease as well as traditional amyloid beta and tau pathology. The purinergic P2X7 receptor and NLRP3 inflammasome signalling are two of the main types of inflammatory mechanism induction to be found to be controlling the activation of microglia and long-term maintenance of inflammatory signals in the brain with Alzheimer disease. Carnosic acid is a natural phenolic diterpene compound which is mainly produced by rosemary and has received interest due to its strong antioxidant behavior as well as anti-inflammatory effects. In preclinical studies of rat models of Alzheimer disease, carnosic acid positively affects cognitive behavior, neuroinflammatory reactions, oxidative stress, and P2X7 receptor-mediated NLRP3 inflammasome activation. Carnosic acid is a multi-target therapeutic agent by blocking upstream stress and downstream inflammatory pathways. The article is a review that summarizes what is known today as to the role of P2X7 receptor and NLRP3 inflammasome in the pathogenesis of Alzheimer disease and critically assesses whether carnosic acid can act as neuroprotective in preclinical rat models. Mechanistic understandings, comparative study to other treatment therapies, difficulties in clinical translation and future research perspectives are also presented. Altogether, carnosic acid is a potentially valid candidate to include in inflammation-based therapeutic approaches in the case of Alzheimer disease.

Hesperidin as a Neuroprotective Agent in Parkinson’s Disease: Mechanistic Insights and In Silico Validation