The Underlying Mechanism of Paeonia lactiflora Pall. in Parkinson’s Disease Based on a Network Pharmacology Approach

Abstract

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide, yet as of currently, there is no disease-modifying therapy that could delay its progression. Paeonia lactiflora Pall. is the most frequently used herb in formulas for PD in Traditional Chinese Medicine and also a potential neuroprotective agent for neurodegenerative diseases, while its mechanisms remain poorly understood. In this study, we aim to explore the underlying mechanism of P. lactiflora in treating PD utilizing a network pharmacology approach.Methods: The protein targets of P. lactiflora ingredients and PD were first obtained from several databases. To clarify the key targets, a Protein-Protein-Interaction (PPI) network was constructed and analyzed on the String database, and then enrichment analysis was performed by the Metascape platform to determine the main Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Finally, the Ingredient-Target-Pathway (I-T-P) network was constructed and analyzed by Cytoscape software.Results: Six active ingredients of P. lactiflora (kaempferol, ß-sitosterol, betulinic acid, palbinone, paeoniflorin and (+)-catechin) as well as six core targets strongly related to PD treatment [AKT1, interleukin-6, CAT, Tumor necrosis factor (TNF), CASP3, and PTGS2] were identified. The main pathways were shown to involve neuroactive ligand-receptor interaction, Calcium signaling pathway, PI3-Akt signaling pathway, TNF signaling pathway, and apoptosis signaling pathway. The main biological process included the regulation of neurotransmitter levels.Conclusion:P. lactiflora may retard neurodegeneration by reducing neuroinflammation, inhibiting intrinsic and extrinsic apoptosis, and may improve motor and non-motor symptoms by regulating the levels of neurotransmitters. Our study has revealed the mechanism of P. lactiflora in the treatment of PD and may contribute to novel drug development for PD.

Evaluating the Therapeutic Mechanisms of Selected Active Compounds in Cornus Officinalis and Paeonia Lactiflora in Rheumatoid Arthritis via Network Pharmacology Analysis

“…This is done through a variety of databases and bioinformatic resources, giving us a direction towards future research by identifying specific targets of interest that can be further explored experimentally. The underlying mechanism of Cornus officinalis and Paeonia lactiflora has been predicted using network pharmacology in association with diseases such as ulcerative colitis ( Zhang et al, 2019 ), Alzheimer’s disease ( Zeng et al, 2019 ), Parkinson’s disease ( Du et al, 2020 ), and depression ( Liu et al, 2020 ). Using a variety of network pharmacology resources, we analyzed the potential molecular functions of Cornus officinalis and Paeonia lactiflora pertaining to RA by breaking down the properties of their individual active compounds.…”

Oxypaeoniflorin Prevents Acute Lung Injury Induced by Lipopolysaccharide through the PTEN/AKT Pathway in a Sirt1-Dependent Manner

“…is one of the most common traditional Chinese herbal medicines, which was mainly used for the treatment of liver disease over thousands of years [ 22 ]. As the main component isolated from Paeonia lactiflora Pall., Oxy displays multiple pharmacological actions including antioxidative stress, antiapoptosis, and anti-inflammation [ 23 ] [ 9 , 24 ]. The significant effects of Oxy on oxidative stress, apoptosis, and inflammation suggest a possible application for Oxy in infection and ALI.…”

Paeoniflorin Ameliorates Cognitive Impairment in Parkinson’s Disease via JNK/p53 Signaling

“…PF has numerous biological effects, including anti-in ammatory and immunoregulatory effects , anti-oxidation effects (Yuan et al, 2020) and anti-apoptosis effects (Wei et al, 2021). Moreover, PF is also reported to attenuate cognitive dysfunction in diabetic rats (Sun et al, 2017) and to delay neurodegeneration by reducing neuroin ammation, inhibiting internal, and external cell apoptosis, and improving motor and non-motor symptoms via regulation of neurotransmitter levels in PD (Du et al, 2020). A previous study con rmed that PF exerts its effects against Aβ-induced neuroin ammation by inhibiting NF-κB signaling (Cho et al, 2020).…”