P2X7-Receptor Pathway Involvement in the Anti-Inflammatory Activity of Medicinal Plants

Area of Science:

• Pharmacology and Ethnobotany
• Inflammation research
• Purinergic signaling

Background:

• European folk medicine utilizes plants from Lamiales, Gentianales, and Asterales orders for treating inflammatory disorders.
• The role of purinergic receptor P2X7 activation in inflammation remains largely unexplored.
• Identifying novel anti-inflammatory targets and natural compounds is crucial for therapeutic advancements.

Purpose of the Study:

• To investigate the inhibitory effect of European folk medicinal plant extracts on purinergic receptor P2X7 activation.
• To explore the potential of these plants as a source of novel anti-inflammatory agents targeting P2X7.
• To identify specific compounds responsible for P2X7 inhibition.

Main Methods:

• In vitro bioassay using YO-PRO-1 uptake dye to measure P2X7 activation.
• Screening of plant extracts from European folk medicine.
• Ultra-Performance Liquid Chromatography coupled with Mass Spectrometry (UPLC/MS), dereplication, and metabolomic analysis for compound identification.

Main Results:

• Several plant extracts demonstrated significant inhibition of P2X7 activation (>50% at 0.1 and 1 μg/mL).
• Species from the Scrophularia and Plantago genera were particularly effective.
• Harpagoside, a cinnamoyl-iridoid, was identified as a putative inhibitor of P2X7 activation in Scrophularia extracts.

Conclusions:

• Medicinal plants from Scrophularia and Plantago genera possess compounds that can inhibit P2X7 activation.
• Cinnamoyl-iridoids, such as harpagoside, may represent a new class of P2X7 inhibitors with anti-inflammatory potential.
• This study opens new avenues for researching anti-inflammatory mechanisms involving the P2X7 receptor and cinnamoyl-iridoid-bearing plants.