Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats

Fujiang Wang,Yong Jiang,Ruiyan Li,Kewu Zeng,Jianping Chen,Pengfei Tu

doi:10.3389/fphar.2020.00236

Abstract

BackgroundThe traditional Chinese medicine Cistanche deserticola has been reported to be valid for cardiovascular and cerebrovascular diseases. However, its active components for the protection of ischemic stroke are not clear. We aimed to explore the active components of C. deserticola against ischemic stroke as well as its potential mechanisms.MethodsWe investigated the brain protective effects of extracts from C. deserticola, total glycosides (TGs), polysaccharides (PSs), and oligosaccharides (OSs) in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to assess the cerebral infarction volume, and Evans blue assay was adopted to assess the blood-brain barrier (BBB) permeability. Then, the expressions CD31, α-SMA, PDGFRβ, SYN, PSD95, MAP-2, ZO-1, claudin-5, occludin, Keap-1, and Nrf-2 were analyzed using western blotting or immunofluorescence, and the activities MDA, SOD, CAT, and GSH-Px were analyzed using kits.ResultsTGs treatment remarkably decreased neurological deficit scores and infarction volumes, promoted angiogenesis and neural remodeling, and effectively maintained blood-brain-barrier integrity compared with the model group. Furthermore, TGs significantly decreased MDA levels and increased antioxidant activities (SOD, CAT, and GSH-Px) in brains. Meanwhile, TGs remarkably downregulated Keap-1 expression and facilitated Nrf-2 nuclear translocation. On the contrary, no protective effects were observed for PSs and OSs groups.ConclusionTGs are the main active components of C. deserticola against MCAO/R-induced cerebral injury, and protection is mainly via the Nrf-2/Keap-1 pathway.

Highlights

Strokes are considered to be a major cause of death and disability in the world (Donnan et al, 2008)
We investigated the brain protective effects of extracts from C. deserticola, total glycosides (TGs), polysaccharides (PSs), and oligosaccharides (OSs) in a rat model of middle cerebral artery occlusion-reperfusion (MCAO/R). 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining was used to assess the cerebral infarction volume, and Evans blue assay was adopted to assess the blood-brain barrier (BBB) permeability
TGs treatment remarkably decreased neurological deficit scores and infarction volumes, promoted angiogenesis and neural remodeling, and effectively maintained blood-brain-barrier integrity compared with the model group

Summary

Introduction

Strokes are considered to be a major cause of death and disability in the world (Donnan et al, 2008). The most effective agent and the only FDAapproved drug used for ischemic stroke treatment is recombinant tissue plasminogen activator. A large amount of stroke patients fail to respond to this drug, owing to its narrow therapeutic time window and a serious risk of hemorrhagic complications (Lee et al, 2012; Schellinger and Kohrmann, 2014). A major challenge of thrombolytic treatment is ischemia/reperfusion (I/R) injury, which is considered as a main cause of brain injury and function destruction. Its active components for the protection of ischemic stroke are not clear. We aimed to explore the active components of C. deserticola against ischemic stroke as well as its potential mechanisms

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