Chemical Composition, Protective Effects, and Mechanisms of Volatile Oil from Fructus Gleditsiae Abnormalis with Nasal Administration against Ischemic Injury in HFD and MCAO-Induced Rats

Abstract

Fructus Gleditsiae Abnormalis (FGA) has been used as a traditional Chinese medicine (TCM) for the treatment of stroke caused by phlegm and blood stasis. However, its substance basis and mechanism of action are currently unknown. This study is aimed to analyze the constituents of the volatile oil in FGA (VOFGA) using gas chromatography coupled with mass spectrometry (GC-MS) and explore the underlying effects and mechanisms of VOFGA in the prevention and treatment of ischemia stroke. An in vivo ischemia model was constructed by combination treatment of high-fat diet (HFD) and middle cerebral artery occlusion (MCAO) method. After administration, the cerebral infarction volume, the brain water content, hemorheology, blood lipids, inflammatory factors, oxidative stress indicators, Bax, Bcl-2, and cleaved caspase-3 and histological examination (HE) were determined and observed to explore the underlying effects and mechanisms of VOFGA against ischemia stroke. The results showed that forty components were determined after analyzed by GC-MS, and the percentage content of palmitate, paeonol, violetone, linalool, salpinol, citral, and methyleugenol were 4.69%, 5.2%, 3.56%, 3.31%, 2.42%, 2.65%, and 1.67%, respectively. The high dose of VOFGA could inhibit neurological damage; reduce the cerebral infarction volume and brain water content; improve whole blood viscosity and red blood cell aggregation index at various shear rates; reduce the levels of TG, TC, LDL-C, TNF-α, IL-1β, MDA, and NO; increase the contents of HDL-C, IL-10, and SOD; downregulate the expressions of Bax and cleaved caspase-3 in the ischemic regions; and upregulate the expressions of Bcl-2. These effects implied that VOFGA may exert neuroprotective effects via inhibiting ischemia-triggered oxidative damage-regulating blood lipid factors and reducing the production of proinflammatory mediators against cerebral I/R injury and neuronal apoptosis. The VOFGA presents a potential treatment value for cerebral ischemic stroke, and it may offer insights into discovering new active compounds for the treatment of ischemic stroke.