Neuroprotection of Osthole against Cerebral Ischemia/Reperfusion Injury through an Anti-apoptotic Pathway in Rats

Abstract

Cerebral ischemia/reperfusion (I/R) injury is a major cause of acute brain injury. The pathogenetic mechanisms underlying I/R injury involve apoptosis, inflammation and oxidative stress. Osthole-a plant coumarin compound-has been reported to protect against focal cerebral I/R-induced injury in rats. However, the mechanism remains unknown. Here we hypothesize that osthole acts through inhibition of apoptosis during focal cerebral I/R injury in rats. We induced cerebral I/R injury by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. We randomly assigned 60 rats to three groups (20 rats per group): sham-operated, vehicle-treated I/R, and osthole-treated I/R. We treated rats intraperitoneally with osthole (40 mg/kg) or vehicle 30 min before cerebral ischemia. We harvested the brains for infarct volume, brain water content, histological changes and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining as well as cleaved caspase-3, bax, and bcl-2 levels 24 h after reperfusion. Osthole treatment significantly attenuated cerebral dysfunction and histologic damage induced by I/R injury. Moreover, osthole-treated rats had a dramatic decrease in apoptotic neuronal cells along with a decrease in bax and cleaved caspase-3. The bcl-2 levels increased. Osthole treatment protects the brain from cerebral I/R injury by suppressing cell apoptosis. Thus, osthole may represent a novel practical strategy to prevent cerebral I/R injury.

Comparative Pharmacokinetics of Hydrophilic Components in Salvia miltiorrhiza Bge. and Carthamus tinctorius L. in Rats That Underwent Cerebral Ischemia Reperfusion Using an HPLC-DAD Method

“…Ischemic stroke is a serious threat to human health and is the most frequent cause of permanent disability in adults worldwide (Lozano et al, 2012). The pathophysiological processes in ischemic stroke are diverse, and include inflammation, apoptosis, oxidative stress, intracellular calcium overload, and destruction of the blood brain barrier (BBB) (Tobin et al, 2014;Li et al, 2016;Li et al, 2018a). TCM herbs and their components have been widely used as therapeutic agents in China since ancient times (Sun et al, 2015).…”

Acteoside Attenuates Oxidative Stress and Neuronal Apoptosis in Rats with Focal Cerebral Ischemia–Reperfusion Injury

“…Apoptosis is an autonomic ordered programmed cell death in order to maintain homeostasis, which is controlled by polygenes. 20,21) Several lines of evidence have shown that apoptosis plays an important role in the pathogenesis of various human diseases, including cerebral I/R injury. During cerebral ischemia, both cyclooxygenase-2 and inducible nitric oxide synthase are highly expressed, and induce activated microglial cells to generate ROS.…”

Synthesis and Biological Evaluation of Novel Coumarins withtert‐Butyl and Terpene Substituents

“…Another natural prenylated coumarin is osthole (7-methoxy-8-(3-methylbut-2-en-1-yl)-2H-chromen-2-one) founded in many plants and showed antifungal activity, [18] antioxidant and neuroprotective properties in the brain from cerebral ischemia/reperfusion injury. [19,20] Moreover, it has been revealed that a number of derivatives of 7-hydroxycoumarins containing bicyclic monoterpene substituent at the hydroxy group are capable of enhancing the cytotoxicity of camptothecin. [21] This compounds also demonstrate inhibition activity against influenza virus A/California/07/09 (H1 N1)pdm09.…”