RESUMO
3-n-butylphthalide (NBP) contains one of the main active ingredients of celery seed. It has a series of pharmacological mechanisms, including reconstitution of microcirculation, protection of mitochondrial function, inhibition of oxidative stress, and inhibition of neuronal apoptosis. Based on the complex multi-targeting of NBP pharmacological mechanisms, the clinical applications of NBP are increasing, and more and more clinical studies and animal experiments have focused on NBP. In this study, we used male Sprague Dawley rats as an animal model to elucidate the intervention effect of butylphthalide on high altitude cerebral edema (HACE), and also compared the effect of butylphthalide and rhodiola rosea on HACE. Firstly, we measured the changes of body weight and brain water content and observed the pathological changes of brain tissues. In addition, the contents of inflammatory factors, oxidative stress and brain neurotransmitters were assessed by enzyme-linked immunoassay kits, and finally, the expression of apoptotic proteins in brain tissues was determined by western blotting. The results showed that NBP reduced brain water content, attenuated brain tissue damage, altered inflammatory factors, oxidative stress indicators, and brain neurotransmitter levels, and in addition NBP inhibited the expression of Caspase-related apoptotic proteins. Therefore, NBP has the potential to treat and prevent HACE.
RESUMO
PURPOSE: Organophosphorus compounds (OPs) is a serious threat to human health and life safety, but because of the existence of blood-brain barrier, most of the therapeutic drugs cannot enter the center, reactivate centrally located toxic acetylcholinesterase (AChE), it is urgent to find an efficient treatment method. METHODS: The c(RGDyK) cyclic peptide modified HI-6-loaded brain targeting liposomes [c(RGDyK)-PEG2000HI-6-lipo] were prepared by ammonium sulfate gradient method. The in vitro blood-brain barrier (BBB) model was established, and the function of the liposomes was evaluated. The animal model of DDVP poisoning was established, and the central toxic enzyme reactivation ability of c(RGDyK)-PEG2000HI-6-lipo by both the intravenous and nasal administration route was verified. RESULTS: The HI-6-loaded liposomes with brain targeting function were successfully synthesized and prepared with high encapsulation efficiency (70.23 ± 2.18%), drug loading (2.86 ± 0.07)%, average particle size 242.9 nm (polydispersion index 0.149), and ζ potential -16.2 mV. Combined with the in vitro and in vivo studies, the c(RGDyK)-PEG2000HI-6-lipo has better ability to cross the BBB. In addition, compared with intravenous injection, nasal administration was proved to be more effective against organophosphorus poisoning, and the reactivation rate of brain acetylcholinesterase reached (26.19 ± 7.70)%. CONCLUSION: The prepared c(RGDyK)-PEG2000HI-6-lipo has a better ability to cross BBB. Nasal administration, as a way to bypass the BBB and directly deliver drugs into the brain, effectively improves the bioavailability of HI-6 in the brain. This study holds promise by providing a non-invasive approach to deliver water-soluble oxime antidote into the brain and reactivate central acetylcholinesterase via the naso-brain route.
