Research Progress on the Mechanism of Ginsenosides in the Treatment of Parkinson’s Disease

Parkinson’s disease (PD) is a neurodegenerative disorder of the central nervous system with a complex pathogenesis. Current conventional medicines are predominantly symptomatic treatments, which fail to reverse neuronal degeneration and often induce severe motor complications following long-term administration. In this context, the advantages of the multi-target holistic regulation provided by traditional Chinese medicine have become increasingly prominent. As the core active ingredients of Panax ginseng, ginsenosides can penetrate the blood–brain barrier and exhibit broad neuroprotective prospects in PD treatment. This article systematically reviews the neuroprotective mechanisms of different configurations of ginsenosides—mainly including protopanaxadiol (PPD) and protopanaxatriol (PPT) saponins—against PD. Studies indicate that PPD-type saponins (e.g., Rb1, Rg3, Rd) excel in directly inhibiting the abnormal aggregation of α-synuclein (α-syn), reducing oxidative stress, and preventing neuronal apoptosis. Conversely, PPT-type saponins (e.g., Rg1, Re) demonstrate significant advantages in suppressing microglia-mediated neuroinflammation, improving mitophagy, and regulating lipid metabolism networks. Furthermore, this review highlights a novel intervention strategy utilizing ginsenosides based on antioxidation and iron metabolism regulation. By maintaining the homeostasis of iron transport proteins such as DMT1 (Divalent Metal Transporter 1) and FPN1 (Ferroportin 1), and activating the Nrf2/xCT/GPX4 signaling axis, these compounds effectively block the vicious cycle of “iron deposition-oxidative stress-lipid peroxidation (LPO),” thereby inhibiting ferroptosis in dopaminergic neurons. In summary, structurally diverse ginsenosides exhibit distinct characteristics in targeting the core pathological events of PD. The scientific combination of ginsenoside monomers with different mechanisms in the future holds promise for constructing a comprehensive multi-target neuroprotective network, providing a solid theoretical foundation for novel ginsenoside-based combination therapies against PD.