• Journal of Life Science
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• v.23 no.2
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• pp.207-212
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• 2013

In this paper, we investigated whether resveratrol could induce the expression of cysteine-rich angiogenic inducer 61 (CYR61), which is a member of the CCN families. We showed that resveratrol up-regulated CYR61 protein expression in three different human colorectal cancer cell lines. In addition, resveratrol induced CYR61 protein expression in a dose- and time-dependent manner in a HCT116 cell line. To investigate the relationship between various biological activities of resveratrol and CYR61 expression, HCT116 cells were incubated with several NSAIDs, antioxidants, or resveratrol. Interestingly, resveratrol only induced CYR61 protein expression. The expression of CYR61 was not related to the presence of p53. A promoter assay revealed that the 786-bp promoter region (-732/+54) contains a regulatory region and that indole-3-carbinol and 6-gingerol could not induce CYR61 expression. In conclusion, our results indicate up-regulation of CYR61 is extremely resveratrol specific. The results can help to shed light on the unique biological function of resveratrol.

• Korean Journal of Food Science and Technology
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• v.43 no.1
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• pp.114-118
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• 2011

Resveratrol is a polyphenolic compound frequently found in the diet, and its physiological actions have been extensively investigated. In the present study, modulation of the antioxidant and cytotoxic properties of resveratrol at different pHs by various antioxidants were investigated. To measure its antioxidant effects, resveratrol was incubated at different pHs, including 6.5, 7.4, and 8.0. Resveratrol incubated at pH 6.5 showed significantly higher DPPH radical scavenging activity, whereas resveratrol incubated at pH 8.0 did not show antioxidant effects. Resveratrol produced much higher amounts of $H_2O_2$ at pH 8.0 than 7.4. The cytotoxic effects of resveratrol on HeLa cells were significantly enhanced by several antioxidants, including superoxide dismutase, N-acetyl cysteine, glutathione, and ascorbic acid. The present results suggest that resveratrol shows anti- or pro-oxidant effects in different cellular organelles according to the pH conditions, and blocking of reactive oxygen species from resveratrol enhances its cytotoxic effects.

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.470-476
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• 2012

Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol ($100{\mu}M$) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells.

• Korean Journal of Plant Resources
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• v.27 no.5
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• pp.567-575
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• 2014

Resveratrol is a naturally occurring stilbene which is safe and well-described compound with a potent anti-inflammatory activity. Recent studies suggested that resveratrol suppressed various inflammation mediated diseases such as asthma, chronic colitis, rheumatoid arthritis, and type 1 diabetes. These studies indicated that resveratrol might directly modulate $CD4^+$ helper T cells (Th cells)-mediated immune responses. However, it is not fully elucidated whether resveratrol directly regulates $CD4^+$ Th cell activation and differentiation. In the present study, $CD4^+$ Th cells were purified from C57BL/6 and treated with various concentrations of resveratrol. We found that resveratrol directly suppressed $CD4^+$ Th cells activation, leading to a defect in T cell proliferation. When $CD4^+$ Th cells were treated with resveratrol, cytokine production was also significantly reduced in a dose dependent manner. In accordance with these results, resveratrol even inhibited $CD4^+$ Th cells differentiation into Th1, Th2 or Th17, which produces IFN-${\gamma}$, IL-4 or IL-17 respectively. We also found that resveratrol could induce apoptosis of $CD4^+$ T cells at a high concentration. Our data demonstrated that resveratrol inhibited directly $CD4^+$ Th cells activation and differentiation. It suggests that resveratrol could be an efficient therapeutic strategy for autoimmune diseases in which $CD4^+$ Th cells play a critical role.

• Korean Journal of Poultry Science
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• v.42 no.2
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• pp.147-156
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• 2015

This study was conducted to investigate the effects of dietary resveratrol on growth performance, blood biochemical parameters, immunoglobulin, and blood antioxidant activity in broiler chicks. Three hundred twenty one-day old broiler chicks were divided 8 treatments (C(-), basal diet; C(+), basal diet with antibiotics; DL-${\alpha}$-tocopherol 20 IU; DL-${\alpha}$-tocopherol 200 IU; resveratrol 20 ppm; resveratrol 200 ppm; methylated resveratrol 20 ppm; methylated resveratrol 200 ppm) with 4 replicates and 10 birds per replicate. Birds were reared for 35 days, and, at the age of 35 days, eight birds of average weight from each replicate were selected for blood samples collection. There were no significant differences on feed intake and feed conversion ratio. But final body weight and weight gain in antibiotics, resveratrol and methylated resveratrol treatments were significantly higher than no-antibiotics and ${\alpha}$-tocopherol treatments (P<0.05). There were no significant differences on carcass rate and relative organ weights among treatments, however, weights of liver and bursa of februcius in antibiotics, resveratrol and methylated resveratrol treatment were lower than other treatments. Weight of pancreas was high in resveratrol and methylated treatment. On the cecal microflora (total microbes, Coliform bacteria, Salmonella spp., and lactic acid bacteria), these in resveratrol and methylated resveratrol treatments didn't show the differences compared with those in no-antibiotics, antibiotics, and ${\alpha}$-tocopherol treatments. In the serum, there were no significant differences on creatinine, blood urea nitrogen (BUN), total protein, albumin, globulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among treatments, though globulin contents of reseveratrol 200 ppm and methylated resveratrol 20 ppm treatments decreased compared to those of other treatments. Immunoglobulin (IgA, IgG and IgM) were significantly decreased in antibiotics and resveratrol treatments compared to that of no-antibiotics and ${\alpha}$-tocopherol treatments (P<0.05). Superoxide dismutase (SOD) like activity tended to increase in resveratrol groups (P<0.05), however, there was no significant difference on malondiakdehyde (MDA) content among treatments. In conclusion, these results showed that resveratrol derived from mulberry can be used as alternative of antibiotics through improvement of broiler's performance and maintain of health.

• Journal of Microbiology and Biotechnology
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• v.31 no.12
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• pp.1692-1700
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• 2021

Glycosylation of resveratrol was carried out by using the amylosucrase of Deinococcus geothermalis, and the glycosylated products were tested for their solubility, chemical stability, and biological activities. We synthesized and identified these two major glycosylated products as resveratrol-4'-O-α-glucoside and resveratrol-3-O-α-glucoside by nuclear magnetic resonance analysis with a ratio of 5:1. The water solubilities of the two resveratrol-α-glucoside isomers (α-piceid isomers) were approximately 3.6 and 13.5 times higher than that of β-piceid and resveratrol, respectively, and they were also highly stable in buffered solutions. The antioxidant activity of the α-piceid isomers, examined by radical scavenging capability, showed it to be initially lower than that of resveratrol, but as time passed, the α-piceid isomers' activity reached a level similar to that of resveratrol. The α-piceid isomers also showed better inhibitory activity against tyrosinase and melanin synthesis in B16F10 melanoma cells than β-piceid. The cellular uptake of the α-piceid isomers, which was assessed by ultra-performance liquid chromatography (UPLC) analysis of the cell-free extracts of B16F10 melanoma cells, demonstrated that the glycosylated form of resveratrol was gradually converted to resveratrol inside the cells. These results indicate that the enzymatic glycosylation of resveratrol could be a useful method for enhancing the bioavailability of resveratrol.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.8
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• pp.1119-1125
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• 2010

To evaluate resveratrol as a prostate cancer preventive material, we investigated its anti-proliferative and apoptotic effects in RC-58T/h/SA#4 primary human prostate cancer cells. Resveratrol significantly decreased the number of viable RC-58T/h/SA#4 cells in a dose- and time-dependent manner. Resveratrol showed cytotoxicity against RC-58T/h/SA#4, LNCaP, PC-3 human prostate cancer cells with $IC_{50}$ values of 245, 320 and $340\;{\mu}M$, respectively. However the cytotoxic potential of resveratrol against normal RWPE-1 cells was lower ($IC_{50}=982\;{\mu}M$). Resveratrol induced cell death as evidenced by the increased formation of apoptotic bodies, nuclear condensation, sub-G1 phase, and DNA fragmentation. Resveratrol activated initiator caspases 8, and 9 as well as effector caspase 3 in a dose-dependent manner. Furthermore, the general caspase inhibitor z-VAD-fmk significantly inhibited resveratrol-induced apoptosis compared to cells without treatment. These results clearly indicate that resveratrol-induced apoptosis was dependent on caspase activation. Further, resveratrol modulated the down regulation of Bcl-2 (anti-apoptotic), and Bid. However, the level of Bax (pro-apoptotic) remained unchanged. These results suggest that resveratrol induced apoptosis in RC-58T/h/SA#4 cells via a mitochondrial-mediated caspase-dependent pathway, suggesting therapeutic potential against prostate cancer.

• Microbiology and Biotechnology Letters
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• v.44 no.2
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• pp.194-200
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• 2016

Resveratrol, a polyphenolic compound present in many fruits and vegetables such as grapes, mulberries, and peanuts, has been reported to have various biological effects. However, the molecular mechanisms underlying resveratrol-induced apoptosis in A549 ovarian cancer cells are not well understood. In this study, we investigated the effect of resveratrol on A549 lung cancer cells (expressing wild-type p53) and compared it with that observed for SKOV3 ovarian cancer cells (expressing null-type p53). Resveratrol significantly inhibited the viability and proliferation of A549 cells in a concentration- and time-dependent manner, compared with its effects on SKOV3 cells. It also induced A549 cell apoptosis, but did not affect anoikis resistance. Furthermore, the viability and proliferation of p53-knockdown A549 cells were unaffected by the presence of resveratrol. Therefore, we demonstrate that the anticancer effect of resveratrol against A549 lung cancer cells is dependent on the presence of functional p53.

• Natural Product Sciences
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• v.10 no.5
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• pp.248-251
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• 2004

Resveratrol has been reported to possess a variety of biological and pharmaceutical activities. Regardless of its beneficial effects on health, the amount of resveratrol in grapes is very low. In order to induce the resveratrol biosynthesis, the promoter region of a genomic fragment encoding the resveratrol synthase was isolated and a molecular switch was identified which provides us with defining biotic or abiotic inducers that transcriptionally up-regulate the gene expression involved in the resveratrol biosynthesis. We could successfully increase the amount of resveratrol in grapes up to 3-fold by using these environmental factors.

• Biomolecules & Therapeutics
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• v.22 no.1
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• pp.35-40
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• 2014

Resveratrol is a polyphenolic compound found in various natural products such as grapes and berries and possesses anti-cancer, anti-hyperlipidemia, and anti-aging properties. Recently, it has been reported that resveratrol inhibits ${\alpha}$-melanocyte-stimulating hormone signaling, viability, and migration in melanoma cells. However, these effects have not been confirmed in vivo, specifically brownish guinea pigs. To evaluate the potential of resveratrol as a regulator of melanin for hyperpigmentation therapy, the influence of resveratrol on pigmentation was investigated by ultraviolet B-induced hyperpigmentation in brownish guinea pig skin. We found that resveratrol reduced the expression of melanogenesis-related proteins tyrosinase, tyrosinase-related proteins 1 and 2, and microphthalmia-associated transcription factor in melanoma cells. Furthermore, topical application of resveratrol was demonstrated to significantly decrease hyperpigmentation on ultraviolet B-stimulated guinea pig skin in vivo. Based on our histological data, resveratrol inhibits melanin synthesis via a reduction in tyrosinase-related protein 2 among the melanogenic enzymes. This study is the first to provide evidence supporting resveratrol as a depigmentation agent, along with further clinical investigation of resveratrol in ultraviolet B-induced skin disorders such as hyperpigmentation and skin photoaging.