Unveiling the Therapeutic Potential of Natural Products in Alzheimer's Disease: Insights from In Vitro, In Vivo, and Clinical Studies

Nahida Aktary¹Yerim Jeong¹Seungji Oh¹Yeju Shin¹Yoonsoo Sung¹Muntajin Rahman¹Livia Ramos²JinWon Choi¹Han Gyeul Song¹Rosy Iara Maciel De Azambuja Ribeiro²Moon Nyeo Park¹Bonglee Kim^1*

• ¹Kyung Hee University, Seoul, Republic of Korea
• ²Universidade Federal de São João del-Rei, São João del Rei, Minas Gerais, Brazil

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder described as progressive cognitive decline and neuronal dysfunction, affecting millions globally. While current pharmacological treatments provide symptomatic relief and modestly slow disease progression, they fail to address the underlying pathophysiology and are often accompanied by severe adverse effects. This underscores the urgent need for innovative, multi-target therapeutic strategies that can effectively step in AD's complex pathogenesis. Emerging evidence highlights the therapeutic potential of natural products, particularly herbal medicines, as versatile modulators of key pathogenic processes in AD. These compounds exert neuroprotective effects by mitigating oxidative stress, suppressing neuroinflammation, inhibiting tau hyperphosphorylation, and reducing amyloid-beta aggregation. Additionally, they strengthen synaptic plasticity and stabilize mitochondrial function, offering a holistic approach to disease control. This comprehensive review synthesizes findings from network pharmacology, in vitro and in vivo studies, and clinical trials to evaluate the role of natural products in AD treatment. Advances in bioinformatics and systems biology facilitate the mapping of intricate protein-protein interactions, the identification of potential biomarkers, and the clarification of molecular mechanisms underlying AD progression.Integrating phytochemicals with conventional AD medications may improve therapeutic efficacy through synergistic mechanisms; however, pharmacokinetic interactions and safety considerations must be rigorously assessed. Notably, clinical trials investigating compounds such as curcumin, resveratrol, and ginsenosides suggest promising adjunctive benefits when incorporated into established treatment regimens. Furthermore, the convergence of herbal therapeutics with modern pharmacology presents an avenue for customized and integrative AD management. This review also emphasizes advancements in experimental models, including brain organoids and transgenic animals, which serve as crucial platforms for mechanistic studies and therapeutic validation. Ongoing trials on plant-derived compounds continue to pave the way for translational applications, reinforcing the viability of natural product-based interventions. By advocating a multidisciplinary framework that merges traditional medicine, modern pharmacology, and precision medicine, this work contributes to reshaping the AD landscape of therapy. It provides a roadmap for future research, fostering novel treatment paradigms that prioritize efficacy, safety, and sustainability in combating this disastrous disorder.