EGCG protective mitochondrial dysfunction after subarachnoid haemorrhage via inhibition p38 α pathway

• Published in: Journal of functional foods Vol. 23; pp. 115 - 123
• Main Authors: Chen, Ying, Huang, Liyong, Zhang, Huiyong, Sun, Haiyan, Zhou, Wenke
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.05.2016; Elsevier
• Subjects: EGCG; Mitochondrion; Mn-SOD; p38α; ROS; Subarachnoid haemorrhage; Mitochondrion; CCK-8 (PubChem CID:9833444); p38 inhibitor (PubChem CID:4665); Mn-SOD; EGCG; ROS; Calcein-AM (PubChem CID: 4126474); 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolocarbocyanine iodide (PubChem CID: 5353694); (-)-Epigallocatechin-3-gallate (PubChem CID: 65064); Subarachnoid haemorrhage; p38α; DCFH-DA (PubChem CID:104913)
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2016.02.035

•EGCG provided neuroprotective roles by targeting mitochondria.•EGCG reduced the Δψm, mPTP opening and ROS levels after SAH.•EGCG elevated Mn-SOD expression after SAH.•EGCG inhibited MKK3 and p38α expression. (-)-Epigallocatechin-3-gallate (EGCG) is well known for its beneficial health effects in the treatment of central nervous system (CNS) diseases. Here, the neuro-protective effects of EGCG and their potential mechanisms after subarachnoid haemorrhage (SAH) were investigated. Oxyhaemoglobin (OxyHb)-induced cell growth was accompanied with mitochondrial dysfunction, such as mitochondrial membrane depolarisation, excessive opened mitochondrial membrane permeability transition pore (mPTP), and high relative oxygen species (ROS) level. However, EGCG dose-dependently inhibited cell growth after SAH, especially at 50 µM (p < 0.01 vs. SAH) by rescue mitochondrial depolarisation. Thus, excessive opened mPTP was shut down, which resulted in less ROS leaking from mitochondria. In addition, EGCG elevated the suppressed Mn-SOD expression after SAH. Treatment with p38 inhibitor significantly decreased MKK3-p38α activity, through which EGCG down-regulated the mitochondrial dysfunction after SAH. The results shed light on the mechanisms behind the neuro-protective effects of EGCG after SAH by targeting MKK3-p38α induced mitochondrial dysfunction.