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

I don't know why anyone writes these research articles, they never seem to make it to any useful intervention. Obviously stroke hospitals don't care, nothing seems to have been implemented in hospitals since tPA was approved in 1996.  I see NO PROTOCOLS ANYWHERE IN STROKE. If there were effective protocols hospitals would be shouting to high heaven about their success in stroke recovery. But no, all you get from hospitals are useless successes in following processes like Get With the Guidelines or Joint Commission crap.

Oops, I'm not playing by the polite rules of Dale Carnegie,  'How to Win Friends and Influence People'. 

Politeness will never solve anything in stroke. Yes, I'm a bomb thrower and proud of it. Someday a stroke "leader" will ream me out for being truthful by making them look bad, I look forward to that day. 

The latest here:

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

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Pengcheng Fu, Jiachen Liu, Qinqin Bai, ...

First Published May 14, 2020 Research Article

https://doi.org/10.1177/1756286420921083

Article information

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.(So human testing should follow immediately, but with NO STROKE LEADERSHIP NOTHING WILL HAPPEN.)

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.

Keywords dual receptor agonist, hematoma clearance, intracerebral hemorrhage, monascin, peroxisome proliferator-activated receptor γ/nuclear factor-erythroid 2 related factor-2

Introduction

Brain injury after intracerebral hemorrhage (ICH) initially occurs within the first few hours as a result of mass effects due to hematoma formation. Continued insults after primary hemorrhage are believed to be caused by intraparenchymal blood lysis.^1,2 Since hematoma is the chief culprit of brain injury following ICH, appropriate removal of hematomas is crucial to prevent and alleviate early brain insults after ICH. However, surgical removal of hematomas has not achieved the expected results.³ Although preliminary studies suggest that minimally invasive hematoma removal may reduce secondary neurotoxicity,^4,5 the effects of hematoma shrinkage on clinical outcome remain unclear.⁶ Therefore, targeting hematoma clearance by promoting an endogenous garbage scavenging system is promising for ICH.
Peroxisome proliferator-activated receptor (PPAR) -γ, which is a part of the nuclear hormone receptor superfamily, can regulate the expression of CD36 and CD163, which participate in phagocytosis.^7–9 In addition, PPAR-γ agonist enhanced CD36 and CD163 expression, accelerated hematoma resolution, then improved neurological deficits.^9–11 Nuclear factor-erythroid 2-related factor 2 (Nrf2) and PPAR-γ play similar roles in phagocytosis and hematoma resolution following ICH.^8,12–14 Monascin is a natural dual activator of both PPAR-γ and Nrf2, and is produced using a unique and natural fermentation process in China. Monascin constitutes one of the azaphilonoid pigments in the extracts of Monascus pilosus-fermented rice (red mold rice).¹⁵ Our previous study demonstrated that monascin was neuroprotective by facilitating hematoma clearance through the haptoglobin-hemoglobin-CD163 pathway in ICH.^9,16 This study aims to further evaluate the long-term effects of monascin in an experimental ICH.