Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway

Abstract

We assessed the antioxidant potential of narcissoside from Sambucus nigra flowers (elderflowers) in Parkinson’s disease models in vitro and in vivo. The results showed that narcissoside lessened the 6-hydroxydopamine (6-OHDA)-induced increase in reactive oxygen species (ROS) and apoptosis in SH-SY5Y cells. In the 6-OHDA-exposed Caenorhabditis elegans model, narcissoside reduced degeneration of dopaminergic neurons and ROS generation, and also improved dopamine-related food-sensitive behavior and shortened lifespan. Moreover, NCS increased total glutathione (GSH) by increasing the expression of the catalytic subunit and modifier subunit of γ-glutamylcysteine ligase in cells and nematodes. Treatment with a GSH inhibitor partially abolished the anti-apoptotic ability of narcissoside. Furthermore, narcissoside diminished the 6-OHDA-induced phosphorylation of JNK and p38, while rising activities of ERK and Akt in resisting apoptosis. The antioxidant response element (ARE)-luciferase reporter activity analysis and electromobility gel shift assay showed that narcissoside promotes the transcriptional activity mediated by Nrf2. Finally, we found that narcissoside augmented the expression of miR200a, a translational inhibitor of the Nrf2 repressor protein Keap1. Downregulation of Nrf2 and miR200a by RNAi and anti-miR200a, respectively, reversed the neuroprotective ability of narcissoside. In summary, narcissoside can enhance the miR200a/Nrf2/GSH antioxidant pathway, alleviate 6-OHDA-induced apoptosis, and has the neuroprotective potential.

Saffron Petal, an Edible Byproduct of Saffron, Alleviates Dextran Sulfate Sodium-Induced Colitis by Inhibiting Macrophage Activation and Regulating Gut Microbiota

“…Simultaneously, the compound–target network analysis indicated that astragalin, 2″-(6-acetylglucosyl)­astragalin, sucrose, and narcissin were identified as the primary components responsible for the anti-inflammatory properties exhibited by SP extract. Previous studies have verified that both astragalin and low dose of sucrose could effectively alleviate the severity of colitis in mice , and also reported that astragalin and narcissin have potent anti-inflammatory effects against alveolar inflammation, osteoarthritis, and neuroinflammation by down-regulating MAPK and/or PI3K/Akt signaling pathways. − Taken together, these findings collectively indicate that SP extract possesses the ability to alleviate DSS-induced colonic inflammation by suppressing macrophage activation through the inhibition of PI3K/Akt and MAPK signaling pathways.…”

Carpesii fructus extract exhibits neuroprotective effects in cellular and Caenorhabditis elegans models of Parkinson's disease

“…In the context of neurodegeneration in PD, aberrant MAPK signaling has been implicated as a key mediator of neuronal death in response to diverse insults such as 6‐OHDA. 36 In this study, we employed Western blotting to investigate the mechanism of action of CFE. Figure 4A–D shows that CFE dose‐dependently upregulated ERK but downregulated JNK and p38 signaling pathways.…”

Iron homeostasis imbalance and ferroptosis in brain diseases

“…The reserve of GSH is consumed by constant Fenton reaction induced by mass labile iron during stroke and neurodegenerative diseases, leading to a decline in the concentration of GSH as enzymatic reactants, which in turn inhibits GPX4 activity 247 . Moreover, evidence shows that promoting GPX4 activity and supplementation of GSH in neurodegenerative diseases and stroke both can mitigate oxidative stress and inflammatory pathology related to ferroptosis, thereby contributing to better preservation of executive functioning longitudinally 244,248–252 …”

“…247 Moreover, evidence shows that promoting GPX4 activity and supplementation of GSH in neurodegenerative diseases and stroke both can mitigate oxidative stress and inflammatory pathology related to ferroptosis, thereby contributing to better preservation of executive functioning longitudinally. 244,[248][249][250][251][252] Therefore, GSH supplementation appears to be a promising target for stroke and neurodegenerative diseases. However, due to the isolation of BBB and the omnipresent γ-glutamyl transpeptidase, which is responsible for GSH cleavage, GSH supplementation in vitro fails to achieve the ideal effect in neurological protection.…”