Research Progress on the Anti-Neuroinflammatory Effects of Polygonatum cyrtonema Hua Polysaccharides: Focusing on Microglial Regulation Targets in Alzheimer's Disease

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and the accumulation of amyloid-β (Aβ) plaques and neurofibrillary tangles. While therapeutic development has largely focused on the amyloid cascade hypothesis, many clinical trials have failed and attention has now shifted to the role of neuroinflammation and its involvement in AD pathogenesis. Microglia, the resident immune cells of the central nervous system (CNS), exert a dual role in this process: they clear cellular debris and maintain CNS homeostasis. However, when overactivated, they polarize to the pro-inflammatory M1 phenotype, which exacerbates neuronal damage. Polygonatum cyrtonema Hua, a traditional Chinese herbal medicine (TCM) known as “Huangjing”, has significant medicinal value, and Polygonatum cyrtonema polysaccharides (PCP) are its key bioactive component. This review mainly summarizes recent progress in the neuroprotective effects of PCP, focusing on its modulation of microglial function. We study the structure of PCP, investigating the mechanism of PCP inhibiting neuroinflammation through regulation of TLR4/NF-κB, MAPK and Nrf2/HO-1 pathway. Additionally, it explores how PCP promotes the phenotypic transition of microglia from the neurotoxic M1 state to the neuroprotective M2 state. This review integrates in vitro and in vivo findings to evaluate the potential of PCP as a multi-target therapeutic agent for AD. Then it’s about the challenges for bioavailability, and standardization which is looking at all these things so that eventually when we move to the clinical translation, we do know exactly how we’ll do that.