Fermented Brown Sugar Residue Prolongs the <i>Caenorhabditis elegans</i>Lifespan <i>via</i>DAF-16

Purification of biomass ethanol from the products of brown sugar yeast-fermentation produces a large amount of residue. This fermentation residue contains abundant brown sugar-derived nutrients and is mainly used as compost or livestock feed. However, the in vivo physiological effects of oral residue ingestion are not known. The purpose of this study was to elucidate the physiological action and molecular mechanism of fermented brown sugar residue in nematode stress tolerance, aging, and lifespan using Caenorhabditis elegans. Fermented brown sugar residue was divided into two layers, supernatant and precipitate, and each was given to nematodes. Analysis of motility and survival rate under thermal stress revealed reduced mobility and increased survival rate following treatment with fermented brown sugar residue. The survival rate of nematodes under 1% H2O2 was markedly increased by the residue and mitochondrial membrane depolarization was induced and mitochondrial radical oxygen species levels increased. Furthermore, aging dependent reduction of motility was suppressed, and the average life span of nematodes was extended by treatment with fermented brown sugar residue. Moreover, the effects of fermented brown sugar residue on stress tolerance, lifespan elongation, and decreased aging dependent momentum reduction were lost in the daf-16 mutant. Taken together, our results show that the various physiological actions of fermented brown sugar residue, including stress tolerance and lifespan extension, occur via DAF-16.

<i>α</i>-Mangostin Promotes DAF-16-Mediated Thermotolerance in <i>Caenorhabditis elegans</i>

Garcinia mangostana, commonly known as mangosteen, is a tropical fruit with a reddish-purple pericarp. In Southeast Asia, the pericarp has traditionally been used as a medicine to treat various diseases, including inflammation, wounds, and bacterial infections, as well as aging. α-mangostin is an abundant xanthone in the pericarp, and is thought to play a critical role in the medicinal effects of mangosteens. Previous studies have demonstrated numerous beneficial effects of α-mangostin, such as cytotoxicity in cancer cells. However, the effects of this xanthone in in vivo have not yet been studied. In the current study, C. elegans was used to test the in vivo effects of α-mangostin using several bioassays, including fat accumulation, pharyngeal movement (pumping) and heat-stress assays. Quantitative real time PCR (qRT-PCR) was also used to examine the expression of heat shock proteins. The results revealed that α-mangostin appeared to cause an increase in fat accumulation, which correlated with an increase in pharyngeal movement. The thrashing movement of the worms after heat stress also showed a correlation with an increase in heat shock protein mRNA expression.

Physiological Effects of Salmon Milt Nucleoprotein on Movement, Stress Tolerance and Lifespan of <i>C. elegans</i>

In recent years, various physiological functions of salmon milt extract, which consists of nucleic acid and nucleoprotein, have been reported. The objective of this study is to analyze the physiological function and its mechanism of salmon milt extract (NG) on nematodes (C. elegans). The wild type nematode N2 strain was bred on the plate containing of NG for four days, and its body length increased depending on NG concentration. When nematodes were bred with NG for a longer period, average lifespan was increased, and survival rate was increased by up to 20%. Generally, the movement of nematodes decreases with longer breeding period (i.e. aging). Analysis of movement (both gross thrashing movement and local pumping movement) showed that NG suppressed this decrease f movement with aging. Furthermore, the deease of survival rate by heat stress and oxidative stress was suppressed by NG administration. Nile Red staining analysis showed that fat accumulation varied depending on the concentration of NG. RT-PCR analysis revealed that the mRNA expression levels of the stress resistance genes sod-3 and sod-4 were increased. These results indicated that NG administration increased the expression of stress-tolerance-related genes, promoted stress tolerance, increased movement and prolonged lifespan in nematode.

Colocynth (<i>Citrullus colocynthis</i>) Flesh Extract Suppresses Adipogenesis by Down-Regulating Adipogenic Transcription Factors and Their Target Genes in 3T3-L1 Preadipocytes

Citrullus colocynthis, a member of the Cucurbitaceae family, is widely distributed in North Africa. The fruits are recognized for their wide range of medicinal uses and promising pharmaceutical potential. The present study aimed to investigate the anti-obesity effect of the ethanol extract of colocynth flesh (FCEE) in 3T3-L1 cells following treatment at different doses. The viability of 3T3-L1 preadipocytes was analyzed via MTT assay and triglycerides were stained with Oil red O to assess lipid accumulation. Additionally, adipogenesis-related gene expression was quantified via qRT-PCR. FCEE (0 - 150 μg/mL) dose-dependently suppressed intracellular triglyceride accumulation during the adipogenesis by 23% and 66% at 100 and 150 μg/mL, respectively, but did not affect cell viability. Analysis of the time-dependence of the effect of FCEE demonstrated that the greatest anti-adipogenic activity was observed during the early stages of differentiation. FCEE also decreased GPDH activity in a dose-dependent manner, with 98% decrease observed at 150 μg/mL. In addition, at same range of FCEE concentrations, the main transcription factors, including CCAAT/enhancer binding protein α (C/EBPα), peroxisome proliferator activated receptor γ (PPARγ), and sterol regulatory element-binding protein 1c (SREBP-1c), were downregulated by 90%, 89%, and 89%, respectively at 150 μg/mL. As these are the master regulators of adipogenesis. The inhibition of their downstream target genes was also observed. Colocynth may be useful in the treatment of obesity owing to its powerful effects on fat, which result in changes to adipocyte differentiation and fat mobilization.

(–)-Epigallocatechingallate Interferes RANKL/RANK Signal Pathway and Induces Apoptosis during Osteoclastogenesis in RAW264 Cell

Green tea catechin, (–)-epigallocatechin-3-gallate [(–)-EGCG], was found to increase osteogenic functioning in mesenchymal stem cells. This study qualified EGCG, the strongest inhibitory efficiency for receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-activated osteoclastogenesis among other green tea catechins for RAW264, a murine preosteoclast cell line. Moreover, EGCG inhibited tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell formation dose dependently in both single culture and co-culture systems, the expression of transcription factor, nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) and some osteoclastic genes. Especially, EGCG exhibited a strong inhibitory effect on the expression levels of RANK, the receptor of RANKL, and OSCAR, a key co-stimulator of the RANKL/RANK signal. Simultaneously, apoptotic genes expression and Hoechst staining revealed that EGCG induced apoptosis in RAW264. Taken together, these data suggest that the inhibitory effect of EGCG to osteoclastogenesis is associated with a down regulation of RANKL/RANK signal, and increased apoptosis of preosteoclasts.