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 ... -  《-》

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 ... -  《-》

Potential Therapeutic Effects of Policosanol from Insect Wax on Caenorhabditis elegans Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The standard treatments for PD focus on symptom relief rather than attempting to address the underlying degenerative processes completely. This study aimed to evaluate the potential therapeutic effects of policosanol derived from insect wax (PIW) by investigating improvements in disease symptoms represented in Caenorhabditis elegans models of PD. For our assessments, we used the following three models: NL5901, which is a transgenic model for α-synuclein aggregation; wild-type N2 induced with 6-hydroxydopamine (6-OHDA); and 6-OHDA-induced BZ555 as a model for loss of dopaminergic neurons (DNs). Specifically, we examined the effects of PIW treatment on α-synuclein aggregation, the loss of DNs, lipid abundance, and the lifespan of treated organisms. Further, we examined treatment-related changes in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), adenosine triphosphate (ATP), glutathione S-transferase (GST), and superoxide dismutase (SOD), as well as the mRNA production profiles of relevant genes. A 10 µg/mL dose of PIW reduced the aggregation of α-synuclein in NL5901 and suppressed the loss of DNs in 6-OHDA-induced BZ555. Overall, PIW treatment decreased ROS and MDA levels, restored lipid abundance, and prolonged the lifespans of worms in all the three models, which may be associated with changes in the expression profiles of genes related to cell survival and oxidative stress response pathways. Our findings show that PIW alleviated the symptoms of PD in these models, possibly by regulating the stress responses initiated by injuries such as α-synuclein aggregation or 6-OHDA treatment.

Ma C ，Feng Y ，Li X ，Sun L ，He Z ，Gan J ，He M ，Zhang X ，Chen X ... -  《-》

Holothuria scabra extracts exhibit anti-Parkinson potential in C. elegans: A model for anti-Parkinson testing.

Chalorak P ，Jattujan P ，Nobsathian S ，Poomtong T ，Sobhon P ，Meemon K ... -  《-》

N-γ-(L-glutamyl)-L-selenomethionine shows neuroprotective effects against Parkinson's disease associated with SKN-1/Nrf2 and TRXR-1 in Caenorhabditis elegans.

Parkinson's disease (PD) is a common neurodegenerative disease, yet fundamental treatments for the disease remain sparse. Thus, the search for potentially efficacious compounds from medicinal plants that can be used in the treatment of PD has gained significant interest. In many medicinal plants, selenium is primarily found in an organic form. We investigated the neuroprotective potential of an organic form of selenium, N-γ-(L-glutamyl)-L-selenomethionine (Glu-SeMet) in a Caenorhabditis elegans PD model and its possible molecular mechanisms. We used a C. elegans pharmacological PD strain (BZ555) that specifically expresses green fluorescent protein (GFP) in dopaminergic neurons and a transgenic PD strain (NL5901) that expresses human α-synuclein (α-syn) in muscle cells to investigate the neuroprotective potential of Glu-SeMet against PD. We found that Glu-SeMet significantly ameliorated 6-hydroxydopamine (6-OHDA)-induced dopaminergic neuron damage in the transgenic BZ555 strain, with corresponding improvements in slowing behavior and intracellular ROS levels. In addition, compared with clinical PD drugs (L-DOPA and selegiline), Glu-SeMet demonstrated stronger ameliorated effects on 6-OHDA-induced toxicity. Glu-SeMet also triggered the nuclear translocation of SKN-1/Nrf2 and significantly increased SKN-1, GST-4, and GCS-1 mRNA levels in the BZ555 strain. However, Glu-SeMet did not increase mRNA levels or ameliorate the damage to dopaminergic neurons when the BZ555 strain was subjected to skn-1 RNA interference (RNAi). Glu-SeMet also upregulated the mRNA levels of the selenoprotein TRXR-1 in both the BZ555 and BZ555; skn-1 RNAi strains and significantly decreased α-syn accumulation in the NL5901 strain, although this was not observed in the NL5901; trxr-1 strain. We found that Glu-SeMet has a neuroprotective effect against PD in a C. elegans PD model and that the anti-PD effects of Glu-SeMet were associated with SKN-1/Nrf2 and TRXR-1. Glu-SeMet may thus have the potential for use in therapeutic applications or supplements to slow the progression of PD.

Chang CH ，Wei CC ，Ho CT ，Liao VH ... -  《-》