Anti-α-synuclein Toxicity and Anti-neurodegenerative Role of Chrysin in Transgenic Caenorhabditis elegans Models of Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD’s progression via modifying disease-specific pathways. Chrysin is a flavonoid derived from passion flowers and possesses anti-cancer, anti-inflammatory, anti-oxidant, and anti-depression properties. In the present study, we assessed the neuroprotective potential of chrysin in transgenic Caenorhabditis elegans models of PD. We observed that chrysin reduced the aggregative toxicity of α-Syn and diminished DA neuron degeneration induced by 6-hydroxydopamine (6-OHDA), reduced food-sensing behavioral disabilities, and expanded the nematodes’ lifespan. Moreover, chrysin augmented the ubiquitin-like proteasome and superoxide dismutase activities in transgenic C. elegans models. Further, we observed the anti-oxidative role of chrysin by reducing the internal cellular reactive oxygen species levels in 6-OHDA-intoxicated C. elegans. Together, these findings supported chrysin as a possible treatment for PD and encouraged further investigation of chrysin’s mechanism of action as a neuroprotective medicine in the future.

Carnosol Reduced Pathogenic Protein Aggregation and Cognitive Impairment in Neurodegenerative Diseases Models via Improving Proteostasis and Ameliorating Mitochondrial Disorders

“…The deposition of Aβ, polyQ, and α-syn caused by proteostasis imbalance mainly gave rise to neurodegeneration and cognitive decline in NDs. , We previously found that 180 μM CL could significantly delay the occurrence of paralytic behavior in Aβ 1‑42 acute aggregation nematode model CL4176 and polyQ age-related aggregation model AM140 . However, the effect of CL on neuronal homeostasis, proteostasis balance, and mitochondrial homeostasis in NDs was not yet clear, so CL at the same concentration was conducted in this study.…”

“…Further, to deeply investigate the effect of CL on cognitive impairment in HD, the food-sensing ability assay and learning association capacity test were performed on the HA759 strains. Since nematodes exhibited a “basal slowing response” when perceiving food, the changes in basal slowing response levels were measured to assess polyQ mediated cognitive impairment in HD nematodes. , The result revealed that CL treatment obviously improved the HA759 worms’ basal slowing behaviors by 36.15% compared to the control (Figure E). Second, nematodes will associate sodium chloride (NaCl) with hunger and deliberately avoid NaCl after being starved in the presence of NaCl .…”

“…Further, the food-sensing ability is mainly regulated by the nematode's DA neuron circuit, and DA signaling is required for learned association in C. elegans. 26,27 Therefore, the food perception ability and NaCl starvation associative ability assays were applied on the BZ555 strain to detect the effect of CL on cognitive impairment related to DA neuron disorder in PD nematodes, and the results showed that CL treatment could significantly improve the food perception ability and learning association ability of C. elegans (Figure 3C,D). It also suggested that CL might alleviate cognitive impairment in the PD model by improving DA neuron damage.…”

Untargeted Metabolomics Analysis of the Orchid Species Oncidium sotoanum Reveals the Presence of Rare Bioactive C-Diglycosylated Chrysin Derivatives

“…Chrysin may also confer neuroprotection, slowing the pace of cognitive decline in neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease [ 26 ]; the latter has been demonstrated in vivo using transgenic Caenorhabditis elegans disease models [ 66 ]. The administration of 5 and 20 mg/kg chrysin every 28 days also increased sucrose consumption and reduced immobility during the tail suspension test in female C57B/6J mice exposed to chronic unpredictable mild stress as a model of depression [ 67 , 68 , 69 ].…”

Potential anti‐Parkinsonian's effect of S‐(+)‐linalool from Cinnamomum osmophloeum ct. linalool leaves are associated with mitochondrial regulation via gas‐1, nuo‐1, and mev‐1 in Caenorhabditis elegans

“…Several studies have used C. elegans to explore the potential anti‐Parkinsonian's activity and mechanisms of natural products. For example, chrysin, a flavonoid derived from passion flowers, has been shown to have anti‐Parkinsonian activity which links to its antioxidative role in the transgenic C. elegans PD model (Muhammad et al, 2022). Chlorogenic acid and β‐amyrin have been reported to improve Parkisonian's effect in transgenic C. elegans PD model which are associated with autophagy‐related mechanisms (He et al, 2021; Wei, Chang, & Liao, 2017).…”