Shisandra Decoction Alleviates Parkinson’s Disease Symptoms in a Mouse Model Through PI3K/AKT/mTOR Signalling Pathway

Yawen Pan,1 Mojinzi Chen,2 Lulu Pan,3 Qiuling Tong,4 Zhiqing Cheng,3 Sujin Lin,3 Rongrong Pan,3 Mengyuan Chen,1 Yinghao Zhi3 1Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, 325000, People’s Republic of China; 2Physician,Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine, Wenzhou, 325000, People’s Republic of China; 3Department of Rehabilitation Medicine, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, 325000, People’s Republic of China; 4The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Yinghao Zhi, Department of Rehabilitation Medicine, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, Wenzhou, 325000, People’s Republic of China, Tel +86-13758472924, Email [email protected]: The present study aimed to characterize neuroprotective effects of Schisandra Decoction (Sch D) treatment in a mouse model of Parkinson’s disease (PD), and to explore underlying mechanisms focused on the mammalian target of rapamycin (mTOR) signaling pathway.Materials and Methods: 50 male C57 BL/6 mice were randomly assigned to either control (n = 10) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model (n = 40) groups. PD mice were further divided into four groups of ten mice each: MPTP group, LY294002 group, Sch D group, and LY2940002 + Sch D group. Mice from each group were assessed in pole climbing, rotary rod and open field tests. Brain Tyrosine hydroxylase (TH) protein was observed using immunohistochemistry. mRNA levels of PTEN, PI3K and LC3 in brain tissue were measured using RT-PCR. Protein levels of PTEN, PI3K, Akt, p-Akt, mTOR, p-mTOR, p70s6K, p62, LC3II / I, α-synuclein (α-syn), TH in brain tissue were assessed by Western blotting (WB).Results: In behavioral tests, PD mice treated with Sch D showed reduced pole climbing time, longer rotarod duration, and greater distance traveled. In terms of neuroprotection, PD mice in the Sch D group exhibited higher levels of TH protein and enhanced α-syn clearance. Regarding autophagy, compared to the control group, mice in the MPTP group had elevated PTEN protein expression, which inhibited PI3K, p-AKT/AKT, and p-mTOR/mTOR protein levels, decreased LC3II/I protein expression, and increased P62 protein expression. Treatment with Sch D reversed these effects.Conclusion: Sch D reduces α-syn aggregation in the brains of MPTP-induced PD model mice, exerts neuroprotective effects, and improves motor function. Additionally, Sch D inhibits autophagy through the PI3K/AKT/mTOR pathway. The neuroprotective effect of Sch D may involve the suppression of abnormal autophagy and its antioxidant properties, which indirectly reduces α-syn accumulation. Future studies should assess the impact of Sch D on oxidative stress markers to evaluate its antioxidant effects.Keywords: Parkinson’s disease, Shisandra decoction, mTOR signaling pathway, autophagy, traditional Chinese medicine