Atractylenolide-I Ameliorates Motor Deficits and Reduces Inflammation of the Spinal Cord by SIRT1/PGC-1α Pathway in MPTP Subacute Mouse Model of Parkinson’s Disease

Ya Gao,1 Shuyue Li,1 Jian Zhang,1 Yidan Zhang,1 Yuan Zhao,1 Shuming Zhang,2 Lujie Zuo,3 Guofeng Yang1 1Department of Geriatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 2Department of Internal Medicine, Fuping County Hospital, Baoding, Hebei, 073200, People’s Republic of China; 3Department of Otolaryngology, Head and Neck Surgery, Children’s Hospital of Hebei Province, Shijiazhuang, Hebei, 050000, People’s Republic of ChinaCorrespondence: Guofeng Yang, Department of Geriatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email yanggf@hebmu.edu.cnBackground: Parkinson’s disease (PD) is a neurodegenerative movement disorder that impacts various systems, including the substantia nigra (SN) par compacta (SNpc) and extranigral regions like the spinal cord. The presence of persistent inflammation in the SN and spinal cord is associated with movement difficulties in PD. Atractylenolide-I (ATR-I) is a natural sesquiterpene recognized for its anti-inflammatory and neuroprotective effects. This research aimed to assess the impact of ATR-I treatment on motor function and inflammation in MPTP-induced subacute PD mice, particularly focusing on the role of ATR-I in spinal cord inflammation.Methods: The motor functions of the mice were assessed using suspension and gait tests. Dopaminergic neuronal loss in the SNpc and microglial activation in both the SNpc and spinal cord were evaluated through immunofluorescence staining. The levels of inflammatory mediators in the spinal cord were measured using RT-qPCR analysis. The expressions of SIRT1 and PGC-1α in the spinal cord were analyzed through Western blotting and RT-qPCR.Results: ATR-I treatment improved motor deficits in MPTP-induced mice. Moreover, ATR-I reduced the loss of dopamine neurons and microglial activation in the SNpc of MPTP-induced mice. Additionally, ATR-I suppressed spinal cord inflammation by decreasing microglial activation and the mRNA expression of TNF-α, IL-1β, and iNOS in MPTP-induced mice. Interestingly, ATR-I also upregulated SIRT1 and PGC-1α levels in the spinal cord of MPTP-induced mice.Conclusion: These findings suggest that ATR-I exhibits anti-inflammatory and neuroprotective properties in PD. The attenuation of spinal cord inflammation via the SIRT1/PGC-1α pathway may contribute to enhancing motor function, highlighting ATR-I as a potential therapeutic avenue for PD.Keywords: Parkinson’s disease, atractylenolide-I, spinal cord, inflammation, SIRT1, PGC‑1&#x03B1