Long-term outcomes of monascin – a novel dual peroxisome proliferator-activated receptor γ/nuclear factor-erythroid 2 related factor-2 agonist in experimental intracerebral hemorrhage

Abstract

Background: Hematoma is the chief culprit in brain injury following intracranial cerebral hemorrhage (ICH). Noninvasive hematoma clearance could be an option to prevent and alleviate early brain injury after ICH. Peroxisome proliferator-activated receptor γ (PPAR-γ) and nuclear factor-erythroid 2 related factor-2 (Nrf2) facilitate removal of hematoma in ICH. Monascin acts as the natural Nrf2 activator with PPAR-γ agonist, and the long-term effects of monascin following ICH have not been elucidated. Methods: ICH in rats was induced by stereotactic, intrastriatal injection of type IV collagenase. Monascin was administered twice daily by gastric perfusion for 14 days after ICH induction. Long-term neurological scores (T maze, Garcia scales, rotor rod test, and Morris water maze), hematoma volume, as well as iron overload around hematoma and brain atrophy were evaluated at 7, 14, and 28 days after ICH. Results: The results showed that monascin improved long-term neurological deficits, spatial memory performance, learning ability, and brain shrinkage after ICH. Monascin also reduced hematoma volume at 7 days and iron content at 7 and 14 days after ICH. Conclusion: PPAR γ and Nrf2 play a crucial role in hematoma clearance after ICH in rat. As a dual agonist of PPAR γ and Nrf2, monascin improved long-term outcomes by facilitating hematoma clearance, and by attenuating iron overload and brain atrophy after experimental ICH.