Paeoniflorin protects 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson’s disease mice by inhibiting oxidative stress and neuronal apoptosis through activating the Nrf2/HO-1 signaling pathway

Abstract

ObjectivesThis study aimed to explore the neuroprotective effects of paeoniflorin on oxidative stress and apoptosis in 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mice. MethodsThe effects of paeoniflorin on motor function in mice were evaluated by behavioral test. Then substantia nigra of mice were collected and neuronal damage was assessed using Nissl staining. Positive expression of tyrosine hydroxylase (TH) was detected by immunohistochemistry. Levels of malondialdehyde, superoxide dismutase (SOD) and glutathione were measured by biochemical method. terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay was used to detect apoptosis of dopaminergic neurons. Western blotting and real-time fluorescence quantitative PCR were used to detect the protein and mRNA expressions of Nrf2, heme oxygenase-1 (HO-1), B-cell lymphoma-2(Bcl-2), Bax and cleaved caspase-3. ResultsPaeoniflorin treatment significantly ameliorated the motor performance impairment in MPTP-induced PD mice. Moreover, it notably increased the positive expression rate of TH and reduced the damage and apoptosis of dopaminergic neurons in the substantia nigra. Furthermore, paeoniflorin increased the levels of SOD and glutathione and decreased the malondialdehyde content. It also promoted Nrf2 nuclear translocation, increased the protein and mRNA expressions of HO-1 and Bcl-2 and reduced the protein and mRNA expressions of BCL2-Associated X2 (Bax) and cleaved caspase-3. Treatment with the Nrf2 inhibitor, ML385, notably reduced the effects of paeoniflorin in MPTP-induced PD mice. ConclusionsNeuroprotective effects of paeoniflorin in MPTP-induced PD mice may be mediated via inhibition of oxidative stress and apoptosis of dopaminergic neurons in substantia nigra through activation of the Nrf2/HO-1 signaling pathway.

Regulation of mitophagy and mitochondrial function: Natural compounds as potential therapeutic strategies for Parkinson's disease

“…Paeoniflorin, a terpenoid glycoside compound extracted from Paeonia lactiflora Pall, holds significant promise for treating neurological disorders, including stroke, Alzheimer's disease and PD due to its unique biological activities and pharmacological effects, which encompass antioxidative, anti‐inflammatory, autophagy regulation, enhancement of cholinergic nerve function, maintenance of ion channel homeostasis, suppression of neuronal apoptosis, and promotion of neuronal nutrition (Hong et al, 2022). In mouse models of PD induced by MPTP, rotenone or 6‐OHDA, both pretreatment and posttreatment with paeoniflorin could mitigate deficits in motor performance, α‐Syn accumulation and the loss of dopaminergic neurons through several mechanisms: (1) Inhibition of mitochondrial apoptosis by upregulating the Bcl‐2/BAD ratio and Bcl‐2/BAX ratio, downregulating cleaved caspase‐3 expression, and reducing caspase‐3/9 activities; (2) Attenuation of mitochondrial‐related oxidative stress by promoting Nrf2 nuclear translocation, leading to the activation of the Nrf2 pathway and subsequent induction of HO‐1 and SOD expression (Guo et al, 2021; Zhang et al, 2023; Zheng et al, 2017). In MPP + ‐treated PC12 cells, paeoniflorin also has been shown to inhibit α‐Syn aggregation, oxidative stress and apoptosis by modulating the autophagy‐lysosome and ubiquitin‐proteasome pathways (in part by inhibiting acid‐sensing ion channels), ultimately enhancing autophagic activity (Hong et al, 2022; Sun et al, 2011).…”

“…Although literature on enhancing its bioavailability is scarce, nanorelated technologies may hold promise for addressing this challenge. and subsequent induction of HO-1 and SOD expression (Guo et al, 2021;Zhang et al, 2023;Zheng et al, 2017). In MPP + -treated PC12 cells, paeoniflorin also has been shown to inhibit α-Syn aggregation, oxidative stress and apoptosis by modulating the autophagylysosome and ubiquitin-proteasome pathways (in part by inhibiting acid-sensing ion channels), ultimately enhancing autophagic activity (Hong et al, 2022;Sun et al, 2011).…”