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

Abstract

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.