Gelatin-Coated Polycaprolactone Nanoparticle-Mediated Naringenin Delivery Rescue Human Mesenchymal Stem Cells from Oxygen Glucose Deprivation-Induced Inflammatory Stress

Abstract

Ischemic stroke involves pro-inflammatory species, which implicates inflammation in the disease mechanism. Recent studies indicate that the prevalence of therapeutic choice such as stem cell transplantation has seen an upsurge in ischemic stroke. However, after transplantation the fate of transplanted cells is largely unknown. Human mesenchymal stem cells (MSCs), due to their robust survival rate upon transplantation in brain tissue, are being widely employed to treat ischemic stroke. In the present study, we have evaluated naringenin-loaded gelatin-coated polycaprolactone nanoparticles (nar-gel-c-PCL NPs) to rescue MSCs against oxygen glucose deprived insult. Naringenin, due to its strong anti-inflammatory effects, remains a therapeutic choice in neurological disorders. Though, the low solubility and inefficient delivery remain challenges in using naringenin as a therapeutic drug. The present study showed that inflammation occurred in MSCs during their treatment with oxygen glucose deprivation (OGD) and was well overturned by treatment with nar-gel-c-PCL NPs. In brief, the results indicated that nar-gel-c-PCL NPs were able to protect the loss of cell membrane integrity and restored neuronal morphology. Then nar-gel-c-PCL NPs successfully protected the human MSCs against OGD-induced inflammation as evident by reduced level of pro-inflammatory cytokine (TNF-α, IFN-γ, and IL-1β) and other inflammatory biomarkers (COX2, iNOS, and MPO activity). Therefore, the modulation of inflammation by treatment with nar-gel-c-PCL NPs in MSCs could provide a novel strategy to improve MSC-based therapy, and thus, our nanoformulation may find a wide therapeutic application in ischemic stroke and other neuro-inflammatory diseases.

Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects

“…1) and has been reported to be showing keto-enol tautomerism. Specifically, TQ is a tautomeric compound where keto-form is the major configuration which exhibits pharmacological actions (Ahmad et al, 2018a, Ahmad et al, 2018b). TQ is a 10 carbon compound having a basic quinone ring moiety of 6 carbons while the 7th methyl group carbon at position C2 and 8th, 9th and 10th propyl group at position C5.…”

“…It is a solid bright yellow compound having scaly crystals with a melting point of 49–50 °C and gives a characteristic intense smell of pepper. The solubility of TQ varies in the range of 549–669 µg/mL in all aqueous solutions (Ahmad et al, 2018a, Ahmad et al, 2018b). TQ is unstable in aqueous solutions particularly at alkaline pH and also possess severe light sensitivity.…”

“…Plants possess a vast assortment of exuberant and eternal resources of bioactive constituents which are applied for the treatment of numerous diseases. Some of the vital and eminent bioactive constituents of plants include alkaloids, glycosides, tannins, flavonoids, phenolic compounds, resins, lectins, etoposides, tanniposides, fatty acids, waxes, terpenoids, phenolic acids and polypropanoids, etc., (Sut et al, 2018, Ahmad et al, 2018a, Ahmad et al, 2018b). These bioactive constituents exhibit a wide array of medicinal and pharmacological activities like anti-tubercular, anti-cancer, anticoagulant, immunomodulatory, aldehyde oxidase inhibitors, anti-oxidant, antidiabetic, anti-inflammatory, influenza virus neuraminidase inhibitors, antibacterial, antifungal, antiplatelet, anti-degranulating, anti-trypanosomal activities (Rehman et al, 2019, Bhat et al, 2019).…”

Mesenchymal stem cells: a new front emerges in coronavirus disease 2019 treatment

“…Therefore, identifying the correct timing and dose of MSCs, besides MSCs passage number, and route of delivery will be important to achieve favorable outcomes. Equally important may be determining the optimal tissue source of MSCs [92] . It is also important to take into account the fitness of MSCs, as freshly harvested cells may tend to show more robustness post-transplantation.…”

Production of polycaprolactone nanoparticles with hydrodynamic diameters below 100 nm

“…It is a FDA (US Food and Drug Administration) approved polymer that is biodegradable and non‐toxic, and therefore suitable for clinical applications . However, the preparation of nanoparticles out of pure PCL has only been performed in a few studies and resulting nanoparticles had diameters from 190 to 350 nm, although different preparation methods have been used . These sizes are not suitable for the use in drug delivery systems especially if targeting ligands should be added that can further increase nanoparticle size .…”