Neuroprotection of Catalpol for Experimental Acute Focal Ischemic Stroke: Preclinical Evidence and Possible Mechanisms of Antioxidation, Anti-Inflammation, and Antiapoptosis.

Xia-Wei Zheng,Guo-Qing Zheng,Wen-Ting Yang,Ji-Chen Ruan,Chun-Shuo Shan,Shuang Chen,Qing-Qing Xu

doi:10.1155/2017/5058609

Abstract

Neuroprotection is defined as using a therapy that affects the brain tissue in the still-viable ischemic penumbra to salvage or delay the infarction. Catalpol, the main active principle of the root of Radix Rehmanniae, was reported to have pleiotropic neuroprotective effects in neurodegenerative diseases including ischemic stroke. Here, we evaluated the neuroprotective effects of catalpol in experimental acute ischemic stroke. Studies on catalpol in animal models of acute ischemic stroke were identified from 6 databases. Twenty-five studies involving 805 animals were included. Twelve comparisons showed significant effects of catalpol on decreasing infarct size according to 2,3,5-triphenyltetrazolium chloride staining compared with the control (P < 0.05). One study reported significant effect of catalpol on reducing infarct size according to magnetic resonance imaging scan compared with the control (P < 0.05). Meta-analysis of these studies indicated that catalpol significantly improved the neurological function score according to Zea Longa score, Bederson score, balance beam-walking test, adhesive removal test, bar-grasping score, and corner test compared with the control (P < 0.05). In conclusion, catalpol exerted neuroprotective effects for experimental acute focal ischemic stroke, largely through reducing oxidative reactions, inhibiting apoptosis, and repressing inflammatory reactions and autophagy. However, these apparently positive findings should be interpreted with caution because of the methodological flaws.

Highlights

Neuroprotection refers to the concept of using a therapy that affects the brain tissue in the still-viable ischemic penumbra to salvage or delay the infarction [1, 2]
Experimental studies of catalpol for acute focal ischemic stroke were identified from PubMed, Web of Science, Excerpta Medica Database (EMBASE), Wanfang Data information site, Chinese National Knowledge Infrastructure (CNKI), and VIP information database
After reviewing the full text of the remaining 158 papers, 80 studies were excluded because catalpol was not used as a monothrapy; 36 studies were excluded because the animal model was not acute focal cerebral ischemia; 11 studies were removed because the outcome measurement was neither neurological function score (NFS) nor infarct volume (IV); 6 studies were excluded because they are duplicate publications

Summary

Introduction

Neuroprotection refers to the concept of using a therapy that affects the brain tissue in the still-viable ischemic penumbra to salvage or delay the infarction [1, 2]. A wealth of research has been conducted into the development of numerous neuroprotective treatments capable of reducing brain damage following ischemic stroke of animal models [4]. Up to now, clinical trials have not identified efficacious neuroprotective therapies for stroke patients [5]. Given the huge translational gap between these animal studies and clinical trials, seeking or developing innovative neuroprotectants is urgently needed. Recent studies reported that catalpol had pleiotropic neuroprotective effects against hypoxic/ischemic injury, Alzheimer’s disease, and Parkinson’s disease in both in vivo and in vitro models [9]. Catalpol had been found to have antioxidation, anti-inflammation, antiapoptosis, and other neuroprotective properties [9], suggesting the potential neuroprotective effect of catalpol on stroke [10]

Objectives

Methods

Results

Conclusion