Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease.
Parkinson's disease (PD) is a debilitating neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra. Despite extensive research, no definitive cure or effective disease-modifying treatment for PD exists to date. Therefore, the identification of novel therapeutic agents with neuroprotective properties is of utmost importance. Here, we aimed to investigate the potential neuroprotective effects of Carpesii fructus extract (CFE) in both cellular and Caenorhabditis elegans (C. elegans) models of PD.
The neuroprotective effect of CFE in H2O2- or 6-OHDA-induced PC-12 cells and α-synuclein-overexpressing PC-12 cells were investigated by determining the cell viability, mitochondrial damage, reactive oxygen species (ROS) production, apoptosis, and α-synuclein expression. In NL5901, BZ555, and N2 worms, the expression of α-synuclein, motive ability, the viability of dopaminergic neurons, lifespan, and aging-related phenotypes were investigated. The signaling pathway was detected by Western blotting and validated by employing small inhibitors and RNAi bacteria.
In cellular models of PD, CFE significantly attenuated H2O2- or 6-OHDA-induced toxicity, as evidenced by increased cell viability and reduced apoptosis rate. In addition, CFE treatment suppressed ROS generation and restored mitochondrial membrane potential, highlighting its potential as a mitochondrial protective agent. Furthermore, CFE reduced the expression of α-synuclein in wide type (WT)-, A53T-, A30P-, or E46K-α-synuclein-overexpressing PC-12 cells. Our further findings reveal that CFE administration reduced α-synuclein expression and improved its induced locomotor deficits in NL5901 worms, protected dopaminergic neurons against 6-OHDA-induced degeneration in BZ555 worms, extended lifespan, delayed aging-related phenotypes, and enhanced the ability of stress resistance in N2 worms. Mechanistic studies suggest that the neuroprotective effects of CFE may involve the modulation of the MAPK signaling pathway, including ERK, JNK, and p38, whereas the interference of these pathways attenuated the neuroprotective effect of CFE in vitro and in vivo.
Overall, our study highlights the potential therapeutic value of CFE as a neuroprotective agent in the context of PD. Furthermore, elucidation of the active compounds of CFE will provide valuable insights for the development of novel therapeutic strategies for PD.
Zhu FD
，Wang BD
，Qin DL
，Su XH
，Yu L
，Wu JM
，Law BY
，Guo MS
，Yu CL
，Zhou XG
，Wu AG
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Anti-Parkinsonian effects of β-amyrin are regulated via LGG-1 involved autophagy pathway in Caenorhabditis elegans.
Parkinson's disease (PD) is a neurodegenerative disease that is associated with aging and is characterized as a movement disorder. Currently, there is still no complete therapy for PD. In recent years, the identification and characterization of medicinal plants to cure or treat PD has gained increasing scientific interest.
In this study, we investigated a pentacyclic triterpenoid compound, β-amyrin, which is found in many medicinal plants for its anti-Parkinsonian effects, using Caenorhabditis elegans (C. elegans) disease models and their underlying mechanisms.
C. elegans treated or untreated with β-amyrin were investigated for oxidative stress resistance, neurodegeneration, and α-synuclein aggregation assays. The C. elegans ortholog of Atg8/LC3, LGG-1 that is involved in the autophagy pathway was also evaluated by quantitative RT-PCR and transgenic strain experiments.
β-Amyrin exerted excellent antioxidant activity and reduced intracellular oxygen species in C. elegans. Using the transgenic strain BZ555, β-amyrin showed a protective effect on dopaminergic neurons reducing cell damage induced by 6-hydroxydopamine (6-OHDA). In addition, β-amyrin significantly reduced the α-synuclein aggregation in the transgenic strain NL5901. Moreover, β-amyrin up-regulated LGG-1 mRNA expression and increased the number of localized LGG-1 puncta in the transgenic strain DA2123.
The results from this study suggest that the anti-Parkinsonian effects of β-amyrin might be regulated via LGG-1 involved autophagy pathway in C. elegans. Therefore, β-amyrin may be useful for therapeutic applications or supplements to treat or slow the progression of PD.
Wei CC
，Chang CH
，Liao VH
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Ferulic Acid Exerts Neuroprotective Effects via Autophagy Induction in C. elegans and Cellular Models of Parkinson's Disease.
Parkinson's disease (PD) is a complex neurological disorder characterized by motor and nonmotor features. Although some drugs have been developed for the therapy of PD in a clinical setting, they only alleviate the clinical symptoms and have yet to show a cure. In this study, by employing the C. elegans model of PD, we found that ferulic acid (FA) significantly inhibited α-synuclein accumulation and improved dyskinesia in NL5901 worms. Meanwhile, FA remarkably decreased the degeneration of dopaminergic (DA) neurons, improved the food-sensing behavior, and reduced the level of reactive oxygen species (ROS) in 6-OHDA-induced BZ555 worms. The mechanistic study discovered that FA could activate autophagy in C. elegans, while the knockdown of 3 key autophagy-related genes significantly revoked the neuroprotective effects of FA in α-synuclein- and 6-OHDA-induced C. elegans models of PD, demonstrating that FA exerts an anti-PD effect via autophagy induction in C. elegans. Furthermore, we found that FA could reduce 6-OHDA- or H2O2-induced cell death and apoptosis in PC-12 cells. Moreover, FA was able to induce autophagy in stable GFP-RFP-LC3 U87 cells and PC-12 cells, while bafilomycin A1 (Baf, an autophagy inhibitor) partly eliminated the protective effects of FA against 6-OHDA- and H2O2-induced cell death and ROS production in PC-12 cells, further confirming that FA exerts an anti-PD effect via autophagy induction in vitro. Collectively, our study provides novel insights for FA as a potent autophagy enhancer to effectively prevent neurodegenerative diseases such as PD in the future.
Long T
，Wu Q
，Wei J
，Tang Y
，He YN
，He CL
，Chen X
，Yu L
，Yu CL
，Law BY
，Wu JM
，Qin DL
，Wu AG
，Zhou XG
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ResearchGate
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