caenorhabditis-elegans-as-model-system-for-discovering-bioactive

<em>Caenorhabditis elegans</em> as a Model System for Discovering Bioactive Compounds Against Polyglutamine-Mediated Neurotoxicity

Age-related misfolding and aggregation of pathogenic proteins are responsible for several neurodegenerative diseases. For example, Huntington&#39;s ...

South China University of Technology

The inherited polyglutamine (polyQ) expansion diseases are characterized by progressive accumulation of aggregation-prone polyQ proteins, which may provoke proteostasis imbalance and result in significant neurotoxicity. Using polyQ transgenic  models, we find that Kai-Xin-San (KXS), a well-known herbal formula traditionally used to treat mental disorders in China, can alleviate polyQ-mediated neuronal death and associated chemosensory deficiency. Intriguingly, KXS does not reduce polyQ aggregation  as demonstrated by Thioflavin-T test, but does inhibit polyQ aggregation in  models, indicating an indirect aggregation-inhibitory mechanism. Further investigation reveals that KXS can modulate two key arms of the protein quality control system, that is, heat shock response and autophagy, to clear polyQ aggregates, but has little effect on proteasome activity. In addition, KXS is able to reduce oxidative stress, which is involved in proteostasis and neurodegeneration, but has no effect on life span or dietary restriction response. To examine potential interaction of the four component herbs of KXS, a dissection strategy was used to study the effects of differential herbal combinations in  polyQ models. While the four herbs do contribute additively to KXS function,  is found to be the most effective constituent. Taken together, these findings not only demonstrate the neuroprotective ability of KXS but also suggest its potential as a proteostasis regulator in protein aggregation disorders and provide an insight into the mechanism studies of traditionally used complex prescriptions and their rationality.

The Traditional Formula Kai-Xin-San Alleviates Polyglutamine-Mediated Neurotoxicity by Modulating Proteostasis Network in .

Sea cucumbers have been used as food delicacies and traditional medicine for centuries, and their health benefits are partly attributed to their repertoire of proteins. Peptides prepared from the sea cucumber Apostichopus japonicus are reported to have in vitro antioxidant activities. Here, we investigated the in vivo antioxidant capacity of AjPH, a peptide-rich A. japonicus protein hydrolyzate, and found that AjPH is capable of increasing the survival rate and reducing the reactive oxygen species (ROS) level in the animal model Caenorhabditis elegans under increased oxidative stress induced by paraquat. AjPH is also shown to enhance the antioxidant defense system in paraquat-exposed nematodes, including upregulation of superoxide dismutase and catalase activities and reduction of malondialdehyde contents. To explore underpinning antioxidant mechanisms, cellular and chemical assays were used to demonstrate that AjPH not only reduces ROS accumulation in cells but also directly scavenges DPPH free radicals. Further studies indicate that AjPH can decrease age pigments and extend lifespan but does not reduce food intake, body length and brood size of the nematodes, demonstrating its capacity to delay physiological aging. Using activity-guided fractionation by ultrafiltration and gel filtration, we then isolated antioxidant fractions from AjPH and identified the sequences of their composing peptides, which were subjected to in silico analysis for prospective motifs, physicochemical properties and antioxidant potential. Taken together, our results provide an insight into the nutraceutical potential of the sea cucumber protein hydrolyzate for aging and related conditions and also a basis for future mechanistic studies of individual antioxidant peptides.

Antioxidant and anti-aging effects of a sea cucumber protein hydrolyzate and bioinformatic characterization of its composing peptides.

Crassostrea gigas Thunberg and other oysters have been traditionally used in China as folk remedies to invigorate the kidney and as natural aphrodisiacs to combat male impotence.

Article	Year
The Traditional Formula Kai-Xin-San Alleviates Polyglutamine-Mediated Neurotoxicity by Modulating Proteostasis Network in . Rejuvenation research\| PubMed ID: 31985332	2020
Antioxidant and anti-aging effects of a sea cucumber protein hydrolyzate and bioinformatic characterization of its composing peptides. Food & function\| PubMed ID: 32520032	2020
Enzymatic preparation of Crassostrea oyster peptides and their promoting effect on male hormone production. Journal of ethnopharmacology\| PubMed ID: 32918991	2021

Qiangqiang Wang

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