Abstract
Ginsenoside Rb1 (GRb1) has been shown to benefit many central nervous system (CNS) disorders, including stroke. However, its bioavailability is low after oral administration due to poor absorption. Intranasal administration has been considered as an effective method for central nervous system drug delivery for its brain-targeting effect. Here, whether intranasal GRb1 could ameliorate cerebral ischemia/reperfusion injury was investigated. First, the concentration of GRb1 in brain tissues and plasma after intranasal and intravenous delivery was calculated using HPLC-MS/MS methods in male Sprague-Dawley rats (250±10 g). Intranasal GRb1 was considered brain-targeting if the value of the drug targeting index (DTI) was greater than 1. Rats were subjected to 1.5 h middle cerebral artery occlusion (MCAO) and were killed 24 h after reperfusion. The neuroprotective effects were measured using 2,3,5-triphenyltetrazolium chloride (TTC) staining and Nissl staining. Immunoblotting of LC3 and Beclin 1, crucial autophagy-related proteins, was used to monitor the state of autophagy. With a local bioavailability of 10.28-32.48% and DTI of 7.35-23.22 in different brain regions, intranasal GRb1 was determined to be brain-targeting. Less infarct volume and more intact neuronal structure were observed in the GRb1 group. GRb1 also restored the elevation of LC3 and Beclin 1. Our work suggests that intranasal GRb1 exerts brain-targeting effects and that a single dose of intranasal GRb1 immediately after MCAO ameliorates ischemia/reperfusion insult. Autophagy is involved in these beneficial effects.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.