Abstract
BackgroundTreatment of the ischemic stroke has remained a major healthcare challenge. The phenolic compound, sesamol, has shown promising antioxidant and neuroprotective effects, however, fast clearance may negatively affect its efficiency. This, prompted us to incorporate sesamol into the nanostructured lipid carriers (S-NLCs) and evaluate its therapeutic potential in in vitro and in vivo models of ischemic stroke.MethodsS-NLCs formulations were prepared by high-pressure homogenization followed by physicochemical characterization, evaluation of the bioactivity of the optimal formulation in oxygen-glucose deprivation (OGD) and global cerebral ischemia/reperfusion (I/R) injury and implication of phosphatidylinositol 3-kinase (PI3K) pathway in this regard. Two- or three-way ANOVA, Mann-Whitney U test, and Student’s t-test were used for data analysis.ResultsFormation of S-NLCs which exhibited a controlled release profile, was confirmed by scanning electron microscope and differential scanning calorimetry. 1- and 8-h OGD followed by 24 h re-oxygenation significantly reduced PC12 cell viability, increased lactate dehydrogenase activity and the number of condensed nuclei, and induced oxidative stress as revealed by increased malondialdehyde level and decreased glutathione content and superoxide dismutase and catalase activities. Sesamol (80 and 100 μM) reduced the cytotoxicity, oxidative stress, and cellular damage only after 1-h OGD, while, S-NLCs (containing 80 and 100 μM of sesamol) were effective at both time points. Intravenous injections of S-NLCs (20 and 25 mg/kg) into rats markedly attenuated I/R-induced neurobehavioural deficits, cellular damage, and oxidative stress, while, free sesamol failed. Pre-treatment with PI3K inhibitor, LY294002, abolished the protective effects against OGD or I/R.ConclusionsS-NLCs improve the pharmacological profile of sesamol and provide longer lasting protective effects for this phenolic phytochemical. This nanoformulation by activating PI3K pathway may serve as a promising candidate for neuroprotection against the cerebral stroke or other neurodegenerative disorders.Graphical abstractSesamol-loaded NLCs, a promising nanoformulation against the ischemic stroke
Highlights
Treatment of the ischemic stroke has remained a major healthcare challenge
We looked at the role of phosphatidylinositol 3-kinase (PI3K) pathway which is critically involved in the cell proliferation and survival [32, 33]
Characterization of sesamol into the nanostructured lipid carriers (S-nanostructured lipid carriers (NLCs)) S-NLCs dispersions were successfully prepared by a modified high-pressure homogenization technique without signs of phase separation or colour change during at least 1-month visual inspection
Summary
Treatment of the ischemic stroke has remained a major healthcare challenge. The phenolic compound, sesamol, has shown promising antioxidant and neuroprotective effects, fast clearance may negatively affect its efficiency. Antioxidant and neuroprotective effects of the phenolic compounds have been the focus of intense research In this respect, sesamol, the major constituent of sesame seed oil (Sesamum indicum, Linn, Pedaliaceae) has attracted a growing interest due to its high safety profile and wide spectrum of pharmacological activities including the effects against the inflammation, oxidative stress, aging, and depression [6,7,8,9]. NLCs are a smarter generation of drug carriers with high biocompatibility, stability, and drugloading capacity, prolonged drug residence in the target organ, and minimal drug expulsion during the storage [27, 30, 31] This background prompted us to prepare sesamolloaded NLCs (S-NLCs) and evaluate the therapeutic potential of this nanoformulation in both in vitro and in vivo models of ischemic stroke. We looked at the role of phosphatidylinositol 3-kinase (PI3K) pathway which is critically involved in the cell proliferation and survival [32, 33]
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