Coumarin-Based Phytochemicals Decursin, Osthole, and Scoparone As New Lead Compounds for Cerebrovascular Protection in Ischemic Stroke Publisher



Valipour M
Source: European Journal of Medicinal Chemistry Reports Published:2026

Abstract

Ischemic stroke remains a critical global health burden, necessitating further development of cerebrovascular protective agents. Despite the considerable importance of this field, relatively few medicinal chemistry studies have been conducted on the development of new compounds with such therapeutic effects. One of the major limitations in this area is the lack of suitable lead compounds for further optimization and drug development. This challenge is further complicated by the diversity of biological targets involved in cerebrovascular injury and protection, including pathways associated with excitotoxicity, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, and BBB disruption. By reviewing studies from the past two decades, this review highlights three key classes of coumarin-derived small molecules that demonstrate broad neurovascular protective potential in preclinical studies, which include decursin and its analogues decursinol angelate and decursinol, osthole and its analogues suberosin and suberenol, as well as scoparone along with its analogues herniarin, scopoletin, isoscopoletin, esculetin, and daphnetin. Preclinical evidence indicates that these compounds exert their pharmacological effects by modulating different pathological cascades and processes relevant to ischemic injury, especially activation of the Nrf2/HO-1 antioxidant pathway, suppression of NF-κB–mediated neuroinflammation, and preservation of BBB integrity. Previous studies further suggest that these compounds can improve cerebrovascular function by reducing oxidative stress and inflammatory responses, supporting vascular homeostasis under ischemic stroke–related conditions. The diverse spectrum of beneficial activities against cerebrovascular disorders suggests that these molecules can be used as lead candidates for the design and development of novel small-molecules for the prevention/treatment of ischemic stroke. © 2026 The Author. Published by Elsevier Masson SAS. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/