Oligonol promotes anti-aging pathways via modulation of SIRT1-AMPK-Autophagy Pathway

BACKGROUND/OBJECTIVES: Oligonol, mainly found in lychee fruit, is an antioxidant polyphenolic compound which has been shown to have anti-inflammatory and anti-cancer properties. The detailed mechanisms by which oligonol may act as an anti-aging molecule have not been determined. MATERIALS/METHODS: In this study, we evaluated the ability of oligonol to modulate sirtuin (SIRT) expression in human lung epithelial (A549) cells. Oligonol was added to A549 cells and reactive oxygen species production, mitochondrial superoxide formation, and p21 protein levels were measured. Signaling pathways activated upon oligonol treatment were also determined by western blotting. Furthermore, the anti-aging effect of oligonol was evaluated ex vivo in mouse splenocytes and in vivo in Caenorhabditis elegans. RESULTS: Oligonol specifically induced the expression of SIRT1, whose activity is linked to gene expression, metabolic control, and healthy aging. In response to influenza virus infection of A549 cells, oligonol treatment significantly up-regulated SIRT1 expression and down-regulated viral hemagglutinin expression. Oligonol treatment also resulted in the activation of autophagy pathways and the phosphorylation of AMP-activated protein kinase (AMPK). Furthermore, oligonol-treated spleen lymphocytes from old mice showed increased cell proliferation, and mRNA levels of SIRT1 in the lungs of old mice were significantly lower than those in the lungs of young mice. Additionally, in vivo lethality assay revealed that oligonol extended the lifespan of C. elegans infected with lethal Vibrio cholerae. CONCLUSIONS: These data demonstrated that oligonol may act as an anti-aging molecule by modulating SIRT1/autophagy/AMPK pathways.

Protective role of oligonol from oxidative stress-induced inflammation in C6 glial cell

BACKGROUND/OBJECTIVES: Natural products or active components with a protective effect against oxidative stress have attracted significant attention for prevention and treatment of degenerative disease. Oligonol is a low molecular weight polyphenol containing catechin-type monomers and oligomers derived from Litchi chinensis Sonn. We investigated the protective effect and its related mechanism of oligonol against oxidative stress. MATERIALS/METHODS: Oxidative stress in C6 glial cells was induced by hydrogen peroxide (H2O2) and the protective effects of oligonol on cell viability, nitric oxide (NO) and reactive oxygen species (ROS) synthesis, and mRNA expression related to oxidative stress were determined. RESULTS: Treatment with oligonol inhibited NO and ROS formation under cellular oxidative stress in C6 glial cells. In addition, it recovered cell viability in a dose dependent-manner. Treatment with oligonol also resulted in down-regulated mRNA expression related to oxidative stress, nuclear factor kappa-B (NF-kappaB) p65, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), compared with the control group treated with H2O2. In particular, expression of NF-kappaB p65, COX-2, and iNOS was effectively reduced to the normal level by treatment with 10 microg/mL and 25 microg/mL of oligonol. CONCLUSIONS: These results indicate that oligonol has protective activity against oxidative stress-induced inflammation. Oligonol might be a promising agent for treatment of degenerative diseases through inhibition of ROS formation and NF-kappaB pathway gene expression.

Functional Analyses of Oligonol by Novel Neutrophil Activity Measurement System / 日本補完代替医療学会誌

We examined the effects of polyphenols on migratory activity of neutrophils into the hydrogel and their production of reactive oxygen species (ROS). Origonol and lychee polyphenol were diluted to medium in wide-range concentrations. Each solution was added on hydrogel, and the mixture of blood and luminol was layered on it in each tube. The ROS production was measured by luminol-dependent chemiluminescence, whereas the cell count in the hydrogel was quantified as migratory activity of neutrophils. The migratory activity of neutrophils was not affected, whereas ROS production of neutrophils was significantly decreased above 100 μg/ml, but increased below the concentration.<br>

The effect of Oligonol intake on cortisol and related cytokines in healthy young men

This study investigated the effects of Oligonol intake on cortisol, interleukin (IL)-1beta, and IL-6 concentrations in the serum at rest and after physical exercise loading. Nineteen healthy sedentary male volunteers participated in this study. The physical characteristics of the subjects were: a mean height of 174.2 +/- 2.7 cm, a mean weight of 74.8 +/- 3.6 kg and a mean age of 22.8 +/- 1.3 years. Each subject received 0.5 L water with Oligonol (100 mg/day) (n = 10) or a placebo (n = 9) daily for four weeks. The body composition, the white blood cell (WBC) and differential counts as well as the serum cortisol, IL-1beta, and IL-6 concentrations were measured before and after Oligonol intake. The cortisol concentration and serum levels of IL-1beta and IL-6 after Oligonol intake were significantly decreased compared to before treatment (P < 0.01, respectively). In addition, the rate of increase of these factors after exercise was decreased compared to the placebo group. There was no change in the WBC and differential cell counts. These results suggest that oral Oligonol intake for four weeks had a significant effect on inhibition of inflammatory markers in healthy young men.

Preventive Effects of Oligomerized Polyphenol on Estradiol-Induced Prostatitis in Rats

PURPOSE: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS, NIH category III) accounts for 90-95% of prostatitis cases. However, standard treatment has not yet been established. It is known that polyphenols have an inhibitory effect on inflammation by their antioxidative capacity, and oligonol, a polyphenol derivative, has much higher bioavailability and bioactivity than common polyphenols. We investigated the anti-inflammatory effects and mechanisms of oligonol in estradiol-induced prostatitis rat models. MATERIALS AND METHODS: Prostatitis was induced by 17 beta-estradiol (E2) and dihydrotestosterone (DHT) in Wistar male rats (n = 20). Ten rats were placed in the oligonol-treated group and 10 in the E2 + DHT-treated group. The other 10 rats were also included as normal control group. Oligonol (60 mg/kg/day) was administered via gavage tube for 4 weeks. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and tumor necrosis factor-alpha (TNF-alpha) were quantified, and phosphorylation of IkappaBa and histological changes were also evaluated in prostatic tissue. RESULTS: The SOD and GPx activity showed tendencies to increase in the oligonol-treated group compared to the normal control group. TNF-alpha expression was slightly reduced in the oligonol-treated group. Western blotting demonstrated that phosphorylation of IkappaBa in the oligonol-treated group was significantly lower than in the normal control group. The E2 + DHT-treated group revealed severe atrophy of acinar epithelial cells and infiltration of leukocytes and lymphocytes in the prostate, however, the oligonol-treated group showed overall reduction in inflammatory features. CONCLUSION: This study demonstrates that oligonol improves estradiol-induced non-bacterial prostatitis by regulating phosphorylation of IkappaBa. These findings suggest that oligonol has a beneficial effect on prevention and treatment of CP/CPPS.