Abstract
Neurodegenerative diseases (Alzheimer’s, Parkinson’s etc.) causes brain cell damage leading to dementia. The major restriction remains in delivering drug to the central nervous system is blood brain barrier (BBB). The aim of this study was to develop a liposomal drug delivery system of Aphanamixis polystachya leaf extract for the treatment of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. In this study GC-MS analysis is used to determine major constituents of Aphanamixis polystachya leaf extract. Liposomal batches of Aphanamixis polystachya leaf extract was prepared using design of experiment (DoE) and characterized using Malvern zetasizer, transmission electron microscopy (TEM), and FT-IR. Stability study of blank and leaf extract loaded liposome were performed in gastric media. In-vivo neurobehavioral and anti-inflammatory studies were performed on mice and rat model respectively. GC-MS data showed that major constituents of Aphanamixis polystachya leaf extract are 2-Pentanone, different acids (Octadec-9-enoic acid, 5-Hydroxypipeloic acid etc.), and Beta-Elemene etc. Malvern Zetasizer and TEM data showed that liposome batches of Aphanamixis polystachya leaf extract were in the range of 120 - 180 nm. Interactions between process parameters and material attributes found to have more impact on the average particle size and polydispersity of liposome batches compared to the impact of each parameter in isolation. Stability studies data suggest that blank and leaf extract loaded liposomes were stable at gastric conditions after 4 hours. In-vivo neurobehavioural study data indicated that significant improvement in the memory function, locomotor activity and ambulatory performance of dementia induced mice was observed for the liposomal batches compared to merely A. polystachya leaf extract.
Highlights
Phytoconstituents are used to treat cognitive disorders such as Alzheimer’s disease (AD), Dementia and Parkinson’s disease through different approaches including acetylcholinesterase (AChE) inhibition, enhancement of cholinergic activity in CNS, anti-inflammatory, antioxidant and estrogen replacement therapy[12,13,14,15]
CNS depressant and analgesic activities were observed for the methanol extract of A. polystachya leaf[26]; to the best of our knowledge no drug delivery system has been utilized to improve the performance of the A. polystachya plant extracts and its activity against dementia
The major ingredients present in Aphanamixis polystachya leaf extracts are listed in Table 2, (GC-MS chromatogram shown by Fig. 1) including 2-Pentanone, higher fatty acids (Octadec-9-enoic acid, 5-hydroxypipecolic acid, hexadecanoic acid), 2-hydrazino-2-imidazoline and beta-elemene etc. 2-Pentanone and Beta-elemene found to have poor solubility in water
Summary
Phytoconstituents are used to treat cognitive disorders such as AD, Dementia and Parkinson’s disease through different approaches including acetylcholinesterase (AChE) inhibition, enhancement of cholinergic activity in CNS, anti-inflammatory, antioxidant and estrogen replacement therapy[12,13,14,15]. Previous research in ethnopharmacology lead to identifying some potential AChE inhibitors from plant sources including those for memory disorders (Dementia) and neurodegenerative diseases such as AD1216–21. One such medicinal plant containing chemical components with likely therapeutic effects is Aphanamixis polystachya (Wall.) R. Phytochemicals of this plant are related to antioxidant, antimicrobial, anti-diarrheal, thrombolytic, diabetes and cytotoxic activities[22,23,24,25]. This work aimed to develop a liposomal drug delivery system of A. polystachya leaf extracts for the treatment of dementia and the probable mechanism of actions
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