Salidroside inhibited cerebral ischemia/reperfusion-induced oxidative stress and apoptosis via Nrf2/Trx1 signaling pathway

Cerebral ischemia reperfusion injury (CIRI) is still a serious problem threatening human health. Salidroside (SAL) is a natural phenylpropanoid glycoside compound with antioxidant, anti-inflammatory, and anti-ischemic properties. This study investigated the protective mechanism of SAL on middle cere...

Full description

Saved in:
Bibliographic Details
Published in:Metabolic brain disease 2022-12, Vol.37 (8), p.2965-2978
Main Authors: Li, Fuyuan, Mao, Qianqian, Wang, Jinyu, Zhang, Xiaoying, Lv, Xinyan, Wu, Bo, Yan, Tingxu, Jia, Ying
Format: Article
Language:English
Subjects:
Apoptosis
BAX protein
Bcl-2 protein
Biochemistry
Biomedical and Life Sciences
Biomedicine
Caspase-3
Catalase
Cerebral blood flow
Deprivation
Glucose
Health risks
Infarction
Inflammation
Ischemia
Kinases
MAP kinase
Metabolic Diseases
Neurology
Neurosciences
Occlusion
Oncology
Original Article
Oxidative stress
Oxygen
Pheochromocytoma cells
Protein kinase
Proteins
Reperfusion
Retinoic acid
Signal transduction
Signaling
Superoxide dismutase
Thioredoxin
Tretinoin
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Cerebral ischemia reperfusion injury (CIRI) is still a serious problem threatening human health. Salidroside (SAL) is a natural phenylpropanoid glycoside compound with antioxidant, anti-inflammatory, and anti-ischemic properties. This study investigated the protective mechanism of SAL on middle cerebral artery occlusion (MCAO)- and oxygen-glucose deprivation/reoxygenation (OGD/R) model-induced CIRI via regulating the nuclear factor erythroid 2-related factor 2 (Nrf2)/thioredoxin 1 (Trx1) axis. The results indicated that SAL (50 mg/kg or 100 mg/kg, intraperitoneal injection) not only effectively alleviated infarction rate, improved histopathological changes, relieved apoptosis by strengthening the suppression of cleaved caspase-3 and Bax/Bcl-2 proteins and decreased malondialdehyde (MDA) formation, but also increased superoxide dismutase (SOD) and catalase (CAT) activities and upregulated the expressions of Nrf2 and Trx1 on MCAO-induced CIRI rats. SAL also efficiently inhibited apoptosis and decreased oxidative stress in OGD/R-stimulated PC12 cells. Furthermore, blocking the Nrf2/Trx1 pathway using tretinoin, an Nrf2 inhibitor, significantly reversed the protective effect of SAL on OGD/R-induced oxidative stress. Moreover, SAL reduced the expression of apoptosis signal-regulating kinase-1 (ASK1) and mitogen-activated protein kinase (MAPK) family proteins. These results demonstrated that SAL inhibited oxidative stress through Nrf2/Trx1 signaling pathway, and subsequently reduced CIRI-induced apoptosis by inhibiting ASK1/MAPK.
ISSN:0885-7490
1573-7365
DOI:10.1007/s11011-022-01061-x