A Systematic Review on Neuroprotective Effects of Catalpol in Acute Focal Ischemic Stroke and their Possible Mechanisms

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This study aims to systematically review the evidence on the neuroprotective effects of Catalpol in animal models of acute focal ischemic stroke and to determine its potential mechanisms of action. Catalpol is the primary active ingredient extracted from the roots of Radix Rehmanniae. Catalpol is found to have pleiotropic neuroprotective effects in neurodegenerative conditions like ischemic stroke. In this study, neuroprotective effects of Catalpol are explored in experimental acute ischemic stroke. Studies relevant to effects of Catalpol in animal models of acute ischemic stroke were identified from the following databases, PubMed, Wanfang Data information site, Chinese National Knowledge Infrastructure (CNKI), and VIP information database and the time period for the study search was fixed as 2010 to 2022. Methodological quality of the included studies was assessed using the CAMARADES checklist. As per the inclusion criteria, twenty-one studies were included. Six out of eight studies had shown significant impact of Catalpol in reducing infarct size according to 2,3,5-triphenyltetrazolium chloride staining compared with the control (P < 0.05). And two studies that determined infarct size by magnetic resonance imaging did not report any significant effect of Catalpol in infarct size reduction when compared to the control. Several tests were used in the studies to assess neurological function score of the animal models, such as Zea Longa score, Balance beam-walking test, Bederson score, adhesive removal test, muscular strength test, bar-grasping test, corner test, cylinder test, neuromuscular function test and foot-fault test. However, ladder rung walking test, sensorimotor function test, open-field test, horizontal ladder test and novel object recognition test were used each in one of the studies. To conclude, Catalpol exerts neuroprotective effects in animal models of acute focal ischemic stroke, mainly by alleviating oxidative stress, inhibiting apoptosis, and repressing inflammatory reactions and autophagy. However, due to the methodological flaws, such as risk of publication bias due to predominance of Chinese studies and low methodological quality of included studies, these positive findings should be interpreted and analyzed with caution.