Tetrahydrocurcumin ameliorates mtMMP‐9 mediated mitophagy and mitochondria remodeling in Stroke

Abstract

Mitophagy is strongly implicated in stroke. Tetrahydrocurcumin(THC) polyphenolic compound, with antioxidant activities. Therefore objective of this study was to determine whether THC ameliorates mitophagy in stroke by reducing matrix metalloproteinase‐9 (MMP‐9) in hyperhomocystemic mice. There weresix groups of mice: WT, WT/Ischemia(IS),WT/IS+ THC,CBS(−/+), CBS(−/+)/IS and CBS(−/+)/IS+THC. Stroke was performed for1 hour. After 24 hours, mice were injected with THC. The infarct area was measured using TTC staining. Permeability was determined by brain edema and Evans Blue extravasation. PCR and Western blot were used todetermine the expression of MMP‐9, TIMPs, mitochondrial redox stress and LC3‐I/II. Mitochondrial respiratory capacity and mitochondrial permeability transition (MPT) were measured fluorescence‐dye. The mitochondrial superoxide and peroxinitrite were detected by using Mito‐SOX and dihydrorhodamine‐123. The result suggested Brain edema and Evans Blue leakage were reduced after stroke in THC treated group as compared to control group along with reduced brain infarct size. Western blot analysis indicated that THC decreased mitochondrial oxidativedamage and ameliorated the MMP‐9 activation and loss of MPT, in part by increasing the protein and mRNA levels of TIMP‐1 and decreasing TIMP‐2 as compared control. This study suggests a therapeutic role of dietary THC in stroke.