Aims

The aim of the current study was to investigate the protective anti-inflammatory effect of Malvidin-O-Glucoside (MG), a natural anthocyanin present in purple grapes, in LPS-induced inflammasome activation in vitro and in a mouse model of Chronic Unpredictable Stress (CUS). This group advocates for the improvement of inflammasome-targeting agents as a potential therapeutic approach to address immune-inflammatory-based disorders.

Methods

Murine primary cortical microglia culture was prepared to examine MG cytotoxicity and pyroptosis. The activation of NLRP3, NLRC4, and AIM2 inflammasomes was induced to study the inhibitory effect of MG. Caspase-1 activity and cytokine levels were explored. MG was administrated at 12.5mg/kg, daily, 15-days prior, and during CUS. Animals were subjected to two stressors per day for 28 days. Depressive and anxiety-like behavior was monitored using elevated plus maze, sucrose preference test, or forced swim test. MG bioavailability was measured by pharmacokinetics.

Results

MG treatment did not exhibit cytotoxicity in vitro. After LPS-induced inflammation in vitro, MG was able to inhibit NLRC4, NRLP3, and AIM2 inflammasomes, showing its anti-pyroptotic function. Caspase-1 activity was also reduced. After CUS, animals treated showed IL-1β gene downregulation and a decrease in protein levels in the hippocampus. Behavioral studies reported a decrease in anxiety- and depressive-related behavior. Pharmacokinetic studies reveal the presence of two metabolites Malvidin-Glucuronide and Malvidin-Glucoside in both brain and plasma.

Conclusions

This study suggests that the polyphenol MG presents anti-inflammatory potential after LPS-inflammation induction in vitro and in a model of CUS, rendering a putative therapeutic profile to address stress-induced behavioral impairment.

Acknowledgments:Supported by the Altschul Foundation