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2.
Int J Mol Sci ; 21(6)2020 Mar 23.
Article in English | MEDLINE | ID: mdl-32210068

ABSTRACT

Human microbiota is heavily involved in host health, including the aging process. Based on the hypothesis that the human microbiota manipulates host aging via the production of chemical messengers, lifespan-extending activities of the metabolites produced by the oral commensal bacterium Corynebacterium durum and derivatives thereof were evaluated using the model organism Caenorhabditis elegans. Chemical investigation of the acetone extract of a C. durum culture led to the identification of monoamines and N-acetyl monoamines as major metabolites. Phenethylamine and N-acetylphenethylamine induced a potent and dose-dependent increase of the C. elegans lifespan, up to 21.6% and 19.9%, respectively. A mechanistic study revealed that the induction of SIR-2.1, a highly conserved protein associated with the regulation of lifespan, was responsible for the observed increased longevity.


Subject(s)
Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans/physiology , Corynebacterium/metabolism , Gene Expression , Longevity , Metabolome , Microbiota , Mouth/microbiology , Sirtuins/genetics , Animals , Caenorhabditis elegans Proteins/metabolism , Longevity/genetics , Molecular Structure , Sirtuins/metabolism
3.
Article in English | MEDLINE | ID: mdl-31057649

ABSTRACT

Alzheimer's disease (AD) is linked to an extensive neuron loss via accumulation of amyloid-beta (Aß) as senile plaques associated with reactive astrocytes and microglial activation in the brain. The objective of this study was to assess the therapeutic effect of WS-5 ethanol extract in vitro and in vivo against Aß-induced AD in mice and to identify the extract's active constituents. In the present study, WS-5 exerted a significant inhibitory effect on acetylcholinesterase (AChE). Analysis by transmission electron microscopy (TEM) revealed that WS-5 prevented Aß oligomerization via inhibition of Aß 1-42 aggregation. Evaluation of antioxidant activities using 1, 1-diphenyl-2-picrylhydrazyl (DPPH) demonstrated that WS-5 possessed a high antioxidant activity, which was confirmed by measuring the total antioxidant status (TAS). Furthermore, the anti-inflammatory properties of WS-5 were examined using lipopolysaccharide-stimulated BV-2 microglial cells. WS-5 significantly inhibited the lipopolysaccharide-induced production of nitric oxide and two proinflammatory cytokines, TNF-α and IL-6. The memory impairment in mice with Aß-induced AD was studied using the Morris water maze and passive avoidance test. Immunohistochemistry was performed to monitor pathological changes in the hippocampus and cortex region of the mouse brain. The animal study showed that WS-5 (250 mg/kg) treatment improved learning and suppressed memory impairment as well as reduced Aß plaque accumulation in Aß-induced AD. HPLC analysis identified the extract's active compounds that exert anti-AChE activity. In summary, our findings suggest that WS-5 could be applied as a natural product therapy with a focus on neuroinflammation-related neurodegenerative disorders.

4.
Arch Pharm Res ; 42(4): 370, 2019 04.
Article in English | MEDLINE | ID: mdl-30725247

ABSTRACT

The author would like to include conflict of interest statement of the online published article. The correct conflict of interest statement should read as: The authors declare no conflict of interest.

5.
Arch Pharm Res ; 41(7): 743-752, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29978428

ABSTRACT

Aging is a key risk factor for many diseases, understanding the mechanism of which is becoming more important for drug development given the fast-growing aging population. In the course of our continued efforts to discover anti-aging natural products, the active constituent 6-shogaol was isolated from Zingiber officinale Roscoe. The chemical structure of 6-shogaol was identified by comparison of its NMR data with literature values. The lifespan-extending effect of 6-shogaol was observed in a dose-dependent manner in Caenorhabditis elegans that has been widely used as a model organism for human aging studies. Mechanism of such action was investigated using C. elegans models, suggesting that 6-shogaol is capable of increasing stress tolerances via enzyme induction. The proposed mechanism was further supported by observation of the increase in SOD and HSP expressions upon treatment with 6-shogaol in transgenic strains of C. elegans which contain GFP-based reporters. In addition, the mechanism was elaborated by confirming that the effect observed for 6-shogaol is independent from other aging-related factors that are known to affect the aging process of C. elegans.


Subject(s)
Aging/drug effects , Caenorhabditis elegans/drug effects , Caenorhabditis elegans/physiology , Catechols/pharmacology , Zingiber officinale/chemistry , Animals , Antioxidants/analysis , Antioxidants/metabolism , Caenorhabditis elegans/metabolism , Catechols/administration & dosage , Catechols/chemistry , Catechols/isolation & purification , Longevity/drug effects , Models, Animal , Molecular Structure , Stress, Physiological/drug effects
6.
Biomol Ther (Seoul) ; 26(6): 568-575, 2018 Nov 01.
Article in English | MEDLINE | ID: mdl-29534560

ABSTRACT

In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans (C. elegans) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans, and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.

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