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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

Overview
Specialty Neurology
Date 2020 Jun 2
PMID 32477427
Citations 11
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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.

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References
1.
Mendelow A, Gregson B, Rowan E, Murray G, Gholkar A, Mitchell P . Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet. 2013; 382(9890):397-408. PMC: 3906609. DOI: 10.1016/S0140-6736(13)60986-1. View

2.
Wang G, Guo Z, Tong L, Xue F, Krafft P, Budbazar E . TLR7 (Toll-Like Receptor 7) Facilitates Heme Scavenging Through the BTK (Bruton Tyrosine Kinase)-CRT (Calreticulin)-LRP1 (Low-Density Lipoprotein Receptor-Related Protein-1)-Hx (Hemopexin) Pathway in Murine Intracerebral Hemorrhage. Stroke. 2018; 49(12):3020-3029. DOI: 10.1161/STROKEAHA.118.022155. View

3.
Zhao X, Sun G, Zhang J, Strong R, Song W, Gonzales N . Hematoma resolution as a target for intracerebral hemorrhage treatment: role for peroxisome proliferator-activated receptor gamma in microglia/macrophages. Ann Neurol. 2007; 61(4):352-62. DOI: 10.1002/ana.21097. View

4.
Babu R, Bagley J, Di C, Friedman A, Adamson C . Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage-induced secondary brain injury and as potential targets for intervention. Neurosurg Focus. 2012; 32(4):E8. DOI: 10.3171/2012.1.FOCUS11366. View

5.
Tontonoz P, Nagy L, Alvarez J, Thomazy V, Evans R . PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell. 1998; 93(2):241-52. DOI: 10.1016/s0092-8674(00)81575-5. View