Document Type : Original Research Article
Authors
1
Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia; Department of Pharmacy, Faculty of Health Science and Technology, Universitas Binawan, Jakarta 13630, Indonesia
2
Department of Medical Pharmacy, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
3
Department of Chemistry, Faculty of Science, Universitas Brawijaya, Malang 65145, Indonesia
4
Department of Neurology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia
5
Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Chuo-ku, Kumamoto, 860-8555, Japan
Abstract
Objective: Alzheimer’s disease (AD) is characterized by amyloid-β (Aβ) plaques and Tau hyperphosphorylation, processes regulated by key enzymes including β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), presenilin-1 (PSEN1), and glycogen synthase kinase-3β (GSK3β). This pathology is further aggravated by insulin resistance which disrupts neuronal signaling and metabolism. However, current therapies face significant challenges in targeting these interconnected mechanisms simultaneously. This study investigated the modulatory effects of Tinospora crispa (L.) Hook.f. & Thomson (T. crispa) extract on Aβ deposition, Tau hyperphosphorylation, and cognitive function in an AD-like pathological model induced in insulin-resistant rats.
Materials and methods: Rats were subjected to a high-fat high-fructose (HFHF) diet combined with streptozotocin (STZ) to induce AD-like pathology. Cognitive performance was evaluated using the Y-maze, while Aβ and phosphorylated Tau (p-Tau) were assessed by immunohistochemistry (IHC). In silico docking was also performed to evaluate interactions between T. crispa compounds and BACE, PSEN1, and GSK3β.
Results: Treatment with T. crispa (400 mg/kg) improved spatial memory by 93.5% and reduced Aβ by 49.3% and p-Tau by 36.3%, with greater effects than metformin across all three parameters. Docking revealed strong affinities of borapetoside B for BACE and tinoscorside A for PSEN1 and GSK3β, supporting their multi-target activity in AD pathways.
Conclusion: These findings suggest that T. crispa and its active constituents exert multi-target neuroprotective effects by simultaneously modulating amyloidogenic and Tau-related mechanisms. This work advances knowledge by identifying a natural extract with potential to fill a critical therapeutic gap, though further studies are needed to confirm safety, long-term efficacy, and clinical relevance in humans.
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