Tranilast Treatment Attenuates Cerebral Ischemia‐Reperfusion Injury in Rats Through the Inhibition of Inflammatory Responses Mediated by NF‐κB and PPARs

Ischemia‐reperfusion injury (IRI) occurs when blood supply returns to tissue after interruption, which is associated with life‐threatening inflammatory response. Tranilast is a widely used antiallergic agent in the treatment against bronchial asthma and keloid. To study the function of tranilast, we used IRI in rat models. The brain tissues of IRI rats with or without tranilast treatment were collected. Neuronal apoptosis in the brain was detected by terminal deoxynucleotidyl transferase nick end labeling assay, and proinflammatory cytokine levels were measured by quantitative real‐time polymerase chain reaction and enzyme‐linked immunosorbent assay. The expression levels of nuclear factor‐kappa B (NF‐κB), inhibitor of κB (IκB) and peroxisome proliferator‐activated receptors (PPARs) were detected by Western blot. The results showed that tranilast treatment reduced neuronal apoptosis in the brain of IRI rats. Tranilast enhanced the short‐term memory and long‐term memory to novel object recognition paradigm. Tranilast treatment decreased the messenger RNA (mRNA) and protein levels of multiple proinflammatory cytokines, and affected NF‐κB and inhibitor of kappa B protein expressions. Tranilast promoted the expressions of PPAR‐α and PPAR‐γ. Our findings demonstrate that tranilast treatment could attenuate cerebral IRI by regulating the inflammatory cytokine production and PPAR expression. Tranilast is a potential drug for IRI treatment in the clinic.