1School of Pharmaceutical Sciences and Technology, SBSU, Dehradun, Uttarakhand, India (email: sunurawat18@gmail.com)
2Director, School of Pharmaceutical Sciences and Technology, SBSU, Dehradun, Uttarakhand, India
3Director, Himalayan Institute of Pharmacy and Research, Dehradun, Uttarakhand, India
*Corresponding Author: Sushila Rawat, School of Pharmaceutical Sciences and Technology, SBSU, Dehradun, Uttarakhand, India. Email: sunurawat18@gmail.com
Background: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-beta (Aβ) deposition, tau hyperphosphorylation, oxidative stress, mitochondrial dysfunction, and chronic neuroinflammation. Despite advances in symptomatic treatments, effective preventive strategies remain limited. Increasing attention has focused on dietary phytochemicals from South Asian medicinal and culinary traditions as potential multi-target agents capable of modulating key pathological pathways involved in AD.
Objective: This review aims to critically examine the mechanistic, preclinical, and clinical evidence supporting South Asian dietary phytochemicals as preventive strategies against AD, with emphasis on their effects on amyloidogenesis, tauopathy, neuroinflammation, oxidative stress, and mitochondrial dysfunction.
Methods: A narrative synthesis of experimental, translational, and clinical literature was conducted. Evidence from in vitro neuronal models, transgenic animal studies (e.g., APP/PS1 mice), and human clinical trials was evaluated. Particular attention was given to phytochemicals derived from Curcuma longa (curcumin), Withania somnifera, and Piper nigrum (piperine), along with formulation strategies addressing bioavailability challenges.
Results: Mechanistic evidence indicates that South Asian phytochemicals inhibit β-secretase (BACE1) activity, reduce Aβ aggregation, regulate glycogen synthase kinase-3β (GSK-3β) signaling, suppress NF-κB–mediated neuroinflammation, and activate antioxidant pathways such as Nrf2. Preclinical studies demonstrate improved cognitive performance in behavioral paradigms including the Morris water maze, alongside reductions in amyloid burden and phosphorylated tau levels. Early clinical trials suggest potential cognitive and biomarker benefits; however, findings are limited by small sample sizes, heterogeneity of formulations, and short intervention durations. Bioavailability remains a major translational challenge, prompting development of nanoformulations, liposomal systems, bioenhancers such as piperine, and sustained-release technologies.
Conclusion: South Asian dietary phytochemicals exhibit multi-target neuroprotective properties aligned with the complex pathophysiology of AD. While preclinical data are compelling, large-scale, biomarker-guided clinical trials are necessary to establish efficacy. Integration of standardized phytochemical formulations within personalized and preventive neurology frameworks may represent a promising translational pathway toward nutraceutical-based strategies for AD risk reduction.
Keywords: Alzheimer's disease; amyloidogenesis; tauopathy; neuroinflammation; curcumin; ashwagandha; South Asian phytochemicals; oxidative stress; nutraceuticals; preventive neurology.
How to cite this article: Rawat S, Ram V, Kumar P. Targeting Amyloidogenesis, Tauopathy, and Neuroinflammation through South Asian Dietary Phytochemicals: A Preventive Strategy against Alzheimer's Disease. Int J Drug Deliv Technol. 2026;16(12s): 894-907. DOI: 10.25258/ijddt.16.12s.105
Source of support: Nil.
Conflict of interest: None