Immunomodulatory effect of protocatechuic acid on cyclophosphamide induced brain injury in rat: Modulation of inflammosomes NLRP3 and SIRT1

Abstract

Modulation of the inflammasome NLRP3 and SIRT1 are new combat strategy for brain injury protection. The inflammasome activates proinflammatory cytokines releasing interleukin-1β and interleukin-18 which in turn affect the toxins release from immune cells. In addition, SIRT1 controls many biological functions, such as immune response and oxidative stress. Protocatechuic has versatile biological activities and possesses antioxidant, anti-inflammatory and neuroprotective effects. So this work aims to study immunomodulatory effect of protocatechuic acid on cyclophosphamide chemotherapy drug-induced brain injury via modulation of inflammosomes NLRP3 and SIRT1. Rats were randomly assigned to four experimental groups. Normal control group was injected with a single i.p injection of saline. Cyclophosphamide group was injected with a single i.p injection of cyclophosphamide (200 mg/kg). Protocatechuic acid groups were orally administered (50 &100 mg/kg) once daily for 10 consecutive days after cyclophosphamide injection. Protocatechuic acid administration exhibited improvements of the cognition function and memory, a reduction in brain contents of MDA, NLRP3, IL-1 β, NF-κB, IKBKB and Galectin 3 and an elevation of GSH and SIRT1 compared to cyclophosphamide group. In addition, protocatechuic acid administration ameliorated the elevation of caspase 3 and iNOS gene expression and alleviated the neuron degeneration caused by cyclophosphamide. In conclusion, the therapeutic action of protocatechuic acid and its cellular and molecular mechanisms are new insights against various human ailments, especially, neurodegenerative disease as brain injury induced by cyclophosphamide chemotherapy drug in rats through modulation of inflammosomes NLRP3 and SIRT1.