Understanding mechanistic aspect of the therapeutic role of herbal agents on neuroplasticity in cerebral ischemic-reperfusion injury

Stroke is one of the leading causes of death and disability. The only FDA-approved therapy for treating stroke is tissue plasminogen activator (tPA), exhibiting a short therapeutic window. Due to this reason, only a small number of patients can be benefitted in this critical period. In addition, the use of endovascular interventions may reverse vessel occlusion more effectively and thus help further improve outcomes in experimental stroke. During recovery of blood flow after ischemia, patients experience cognitive, behavioral, affective, emotional, and electrophysiological changes. Therefore, it became the need for an hour to discover a novel strategy for managing stroke. The drug discovery process has focused on developing herbal medicines with neuroprotective effects via modulating neuroplasticity. We gather and highlight the most essential traditional understanding of therapeutic plants and their efficacy in cerebral ischemia-reperfusion injury. In addition, we provide a concise summary and explanation of herbal drugs and their role in improving neuroplasticity. We review the pharmacological activity of polyherbal formulations produced from some of the most frequently referenced botanicals for the treatment of cerebral ischemia damage. A systematic literature review of bentham, scopus, pubmed, medline, and embase (elsevier) databases was carried out with the help of the keywords like neuroplasticity, herbal drugs, neural progenitor cells, neuroprotection, stem cells. The review was conducted using the above keywords to understand the therapeutic and mechanistic role of herbal neuroprotective agents on neuroplasticity in cerebral ischemic-reperfusion injury. Neuroplasticity emerged as an alternative to improve recovery and management after cerebral ischemic reperfusion injury. Neuroplasticity is a physiological process throughout one's life in response to any stimuli and environment. Traditional herbal medicines have been established as an adjuvant to stroke therapy since they were used from ancient times and provided promising effects as an adjuvant to experimental stroke. The plants and phytochemicals such as Curcuma longa L., Moringa oliefera Lam, Panax ginseng C.A. Mey., and Rehmannia glutinosa (Gaertn.) DC., etc., have shown promising effects in improving neuroplasticity after experimental stroke. Such effects occur by modulation of various molecular signalling pathways, including PI3K/Akt, BDNF/CREB, JAK/STAT, HIF-1α/VEGF, etc. Here, we gave a perspective on plant species that have shown neuroprotective effects and can show promising results in promoting neuroplasticity with specific targets after cerebral ischemic reperfusion injury. In this review, we provide the complete detail of studies conducted on the role of herbal drugs in improving neuroplasticity and the signaling pathway involved in the recovery and management of experimental stroke.