Potential of phytochemicals in the treatment of Alzheimer disease by modulating lysosomal dysfunction: a systematic review

Abstract

Alzheimer disease (AD) is a primary international health dilemma, especially in elderly populations, due to its progressive nature and its adverse cognitive impact. The dysfunction of lysosomes, which impairs protein degradation and leads to toxic accumulation in neurons, is a pivotal factor in AD. We explore phytochemicals that specifically target lysosomal dysfunction via the activation of autophagy, phagocytosis, and lysosome function, exhibiting anti-inflammatory and antioxidant properties. This study involves extracting and evaluating phytochemicals by exploring multiple databases, Google Scholar, PubMed, the Science Citation Index Expanded (SCIE), and the China National Knowledge Infrastructure (CNKI), integrating contemporary biochemical evidence with TCM principles-highlighting the interconnected roles of deficiency, stasis, and phlegm-to provide a comprehensive therapeutic framework. Key phytochemicals-magnolol, trehalose, and salidroside- demonstrate notable promise in enhancing lysosomal function, reducing amyloid beta accumulation, and improving cognitive outcomes. Addressing traditional theory and modern science, we underline the potential for future research by clarifying the mechanisms of compounds and their effectiveness, which may delay the disease process.

Keywords: Alzheimer disease; Autophagy; Lysosomes; Phagocytosis; Phytochemicals.

Fig. 1

Prisma Flow Chart

Fig. 2

Pathological processes in Alzheimer Disease

Fig. 3

Overview of autophagy pathways

Fig. 4

Network Map of Phytochemical–Protein Interactions Targeting Lysosomal Dysfunction and anti‑inflammatory/antioxidant pathways for Alzheimer Disease therapy. Cluster 1 (left, ~ 50 nodes; orange gradient) groups phytochemicals that exhibit lysosome‑restorative, anti‑inflammatory, and/or antioxidant activity. Cluster 2 (right, ~ 45 nodes; darker orange‑brown) contains key pathological and signalling mediators enriched in lysosomal and autophagy‑related proteins/enzymes. Notes: “↑” represents the up-regulated targets, “↓” represents the down-regulated targets