Objective: To investigate the feasibility and efficacy of paeoniflorin (PF) combined with neural stem cell (NSC) transplantation in treating Parkinson’s disease (PD).

Background: Parkinson’s disease is a chronic progressive neurodegenerative disorder characterized by irreversible loss of dopaminergic neurons in the substantia nigra. Current therapies alleviate symptoms but cannot halt disease progression. NSC transplantation replaces lost neurons but faces challenges including low survival rates and impaired differentiation due to inflammatory microenvironments. Paeoniflorin, a traditional Chinese medicine component with anti-inflammatory and neuroprotective properties, may synergize with NSC therapy by regulating inflammation, though its specific role remains unclear.

Method: NSCs were isolated from embryonic day 14 Sprague-Dawley rat midbrain, with purity confirmed by immunofluorescence. Differentiation medium induced maturation into midbrain dopaminergic neurons (mDA). CCK-8 assays and Calcein-AM/PI staining assessed PF effects on mDA and microglial viability. An LPS-stimulated microglia/mDA co-culture model was established. ELISA measured IL-1β, IL-6, and TNF-α levels; Western blot analyzed TLR4/MYD88/NF-κB and NLRP3 proteins. A PD rat model was created by stereotaxic 6-OHDA injection into the substantia nigra, validated by apomorphine-induced rotations (>7 rotations/minute). mDA cells with/without PF were transplanted into the striatum. TH immunofluorescence and Western blot evaluated neuron survival and inflammation.

Results: NSCs formed Nestin-positive neurospheres and differentiated into TH-positive neurons. PF pretreatment protected mDA from LPS-induced damage without toxicity, enhanced maturation, and reduced IL-1β/IL-6/TNF-α levels. PF suppressed TLR4/MYD88/NF-κB signaling and NLRP3 inflammasome activation. In PD rats, PF+mDA transplantation significantly increased striatal TH+ neuron survival compared to mDA alone, while reducing inflammation.

Conclusion: Paeoniflorin enhances NSC transplantation efficacy by mitigating inflammatory damage, improving cell survival and differentiation. This combination therapy provides a novel strategy for Parkinson’s disease treatment.

Figure 1

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MDS Abstracts - https://www.mdsabstracts.org/abstract/paeoniflorin-combined-with-neural-stem-cell-transplantation-for-parkinsons-disease-synergistic-effects-of-cell-therapy-and-inflammation-regulation/