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Asiatic Acid Fabricated Nanoconstructs to Mitigate Amyloid Beta1-42 Induced Injury in SH-SY5Y Cells In-Vitro and Ameliorates Cognitive Impairment by Dual Cholinesterase Inhibition and Attenuation of Oxidative Stress In-Vivo

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Abstract

Purpose

Asiatic acid (AA) is reported for its neuroprotective potential in Alzheimer’s disease (AD). This present work aimed to develop AA loaded nanostructured lipid carriers (AAN) for targeting the delivery of AA into the brain and ameliorating the cognitive deficits in AD rats.

Methods

AAN was optimized using the Box-Behnken design, considering 3 factors (soya lecithin, tween 80, and high pressure homogenizer (HPH) pressure) as independent variables while particle size (PS), zeta potential (ZP) and entrapment efficiency (EE) were dependent variables. Cytotoxicity assay and internalization studies of AAN were evaluated in SH-SY5Y cells and further neuroprotective efficiency on intracellular amyloid beta (Aβ) aggregation was evaluated in Aβ 1–42 treated cells with thioflavin T (ThT). The behavioral acquisition effects were evaluated in Aβ 1–42 (5 µg/ 5 µL, intracerebroventricular (ICV), unilateral) induced AD model followed by the histology and quantification of neurotransmitters levels.

Results

The optimized AAN revealed desired PS (44.1 ± 12.4 nm), ZP (- 47.1 ± 0.017 mv) and EE (73.41 ± 2.53%) for brain targeting delivery of AA. In-vitro, AAN exhibited better neuroprotective potential than AA suspension (AAS). AA content was 1.28 folds and 2.99 folds heightened in plasma and brain respectively after the i.p. administration of AAN as compared to AAS. The results of pharmacodynamic studies manifested the AAN treatment significantly (p < 0.05) ameliorated the cognitive deficits.

Conclusions

Hence, developed AAN has neuroprotective potential and should be further considered as an unconventional platform in preclinical model for the management of AD.

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Funding

The authors are thankful that this research work was funded by DST-WOS-A, file no: SR/WOS-A/LS-647/2016, Department of Science and Technology (DST), New Delhi, India, Grant No. BT/PR6664/NNT/28/628/2012, Department of Biotechnology (DBT), Government of India, and Institute of Pharmacy and Institute of Science Nirma University for providing all required research facilities.

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  1. Department of Pharmacognosy, Institute of Pharmacy, Nirma University, Ahmedabad, 382481, Gujarat, India

    Tripti Halder, Bharat Patel & Niyati Acharya

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  1. Tripti Halder
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Correspondence to Niyati Acharya.

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Halder, T., Patel, B. & Acharya, N. Asiatic Acid Fabricated Nanoconstructs to Mitigate Amyloid Beta1-42 Induced Injury in SH-SY5Y Cells In-Vitro and Ameliorates Cognitive Impairment by Dual Cholinesterase Inhibition and Attenuation of Oxidative Stress In-Vivo. Pharm Res 40, 197–213 (2023). https://doi.org/10.1007/s11095-022-03428-2

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