Targeted Neuroprotection in Sporadic Alzheimer's Disease: UPLC-ESI-MS/MS Profiling and Bilosome-Mediated Delivery of Crateva magna and Its Endophytic Fungal Extracts.
Aya N Talaat, Mohamed S Elnaggar, Nehal Ibrahim, Iriny M Ayoub, Haidy Abbas, Nesrine El Sayed, Rola M Labib, Abdel Nasser B Singab
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Abstract
Introduction: Crateva magna (Cm) was utilized as a folkloric medicine against neurological disorders.
Objectives: This study aimed to investigate the phytochemical profile of Cm leaf extract and its endophytic fungus, Nigrospora oryzae (No) extract. Additionally, the neuroprotective potential of their optimized bilosomes (BLs) will be assessed as an approach to Alzheimer's disease (AD) treatment.
Materials and methods: UPLC-ESI-MS/MS chemical profiling was performed. In vitro anti-Alzheimer activity of Cm and No extracts was evaluated against AChE and BACE1 enzymes. Cm-BLs and No-BLs were prepared using the thin-film hydration technique. In vivo anti-Alzheimer potential was assessed in a streptozotocin (STZ)-induced sporadic AD mouse model. Behavioral assays, neurochemical assays, RT-PCR analysis, histopathological examination, and immunohistochemical analysis were performed.
Results: Chemical profiling revealed diverse metabolites from various chemical classes. The major class identified in Cm extract was flavonoids, e.g., kaempferol-O-hexoside, whereas in No extract, it was alkaloids, e.g., phenazine carboxamide. The neuropathological markers (Aβ1-42, IL-6, and p-Tau protein) were reduced by ≈50% and 60% in mice receiving Cm-BLs and No-BLs, respectively, relative to the STZ group. Also, the BLs exhibited the greatest ability to downregulate the expression of p-JNK, p-P38, and p-ERK in the brain. Histopathological examination revealed that No-BLs showed the highest protection for the hippocampus and cerebral cortex regions. Also, it revealed a significantly decreased reaction for NFκB in cerebral cortex neurons.
Conclusion: Cm-BLs and No-BLs exhibit considerable potential as novel adjuvant therapies for AD, utilizing natural bioactive compounds to improve the efficiency of targeted drug delivery and enhance therapeutic outcomes.
期刊介绍：
Phytochemical Analysis is devoted to the publication of original articles concerning the development, improvement, validation and/or extension of application of analytical methodology in the plant sciences. The spectrum of coverage is broad, encompassing methods and techniques relevant to the detection (including bio-screening), extraction, separation, purification, identification and quantification of compounds in plant biochemistry, plant cellular and molecular biology, plant biotechnology, the food sciences, agriculture and horticulture. The Journal publishes papers describing significant novelty in the analysis of whole plants (including algae), plant cells, tissues and organs, plant-derived extracts and plant products (including those which have been partially or completely refined for use in the food, agrochemical, pharmaceutical and related industries). All forms of physical, chemical, biochemical, spectroscopic, radiometric, electrometric, chromatographic, metabolomic and chemometric investigations of plant products (monomeric species as well as polymeric molecules such as nucleic acids, proteins, lipids and carbohydrates) are included within the remit of the Journal. Papers dealing with novel methods relating to areas such as data handling/ data mining in plant sciences will also be welcomed.
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