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

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline, synaptic dysfunction, and irreversible neuronal loss. Despite extensive research, currently approved pharmacological therapies offer only symptomatic relief and fail to halt disease progression. Increasing evidence identifies chronic neuroinflammation, particularly microglia-driven inflammatory signaling, as a central contributor to AD pathology. Among inflammatory regulators, the purinergic P2X7 receptor and downstream NLRP3 inflammasome axis play a pivotal role in sustaining neuroinflammatory cascades, oxidative stress, and neuronal damage. Consequently, this signaling axis has emerged as a promising therapeutic target. Herbal medicines, with their intrinsic multi-target pharmacology and favorable safety profiles, offer an alternative strategy for addressing the multifactorial nature of AD. Cuscuta reflexa Roxb. (Amarbel), a parasitic medicinal plant widely used in traditional systems of medicine, is rich in flavonoids, phenolic acids, glycosides, alkaloids, and lignans with documented anti-inflammatory, antioxidant, and neuroprotective properties. This review critically examines the neurotherapeutic potential of Cuscuta reflexa as a multi-target modulator of the P2X7–NLRP3 inflammasome axis in Alzheimer’s disease. We integrate evidence from AD pathophysiology, purinergic signaling, phytochemistry, and experimental pharmacology to propose a mechanistic framework through which Cuscuta reflexa may attenuate chronic neuroinflammation, preserve synaptic integrity, and support neuronal survival. Finally, translational challenges, formulation strategies, and future research directions are discussed to support the development of Cuscuta reflexa-based interventions for neurodegenerative disorders.