Protopanaxadiol-Enriched Rice Exerted Antiadipogenic Activity during 3T3-L1 Differentiation and Anti-Inflammatory Activity in 3T3-L1 Adipocytes.

Ginseng is a traditional medicine with health benefits for humans. Protopanaxadiol (PPD) is an important bioactive compound found in ginseng. Transgenic rice containing PPD has been generated previously. In the present study, extracts of this transgenic rice were evaluated to assess their antiadipogenic and anti-inflammatory activities. During adipogenesis, cells were treated with transgenic rice seed extracts. The results revealed that the concentrations of the rice seed extracts tested in this study did not affect cell viability at 3 days post-treatment. However, the rice seed extracts significantly reduced the accumulation of lipids in cells and suppressed the activation of CCAAT/enhancer-binding protein α (C/EBPα) and peroxisome proliferator-activated receptor γ (PPARγ), which in turn inhibited the expression of adipogenesis-related mRNAs, such as adiponectin, PPARγ, C/EBPα, sterol regulatory element-binding protein 1, glucose transport member 4, and fatty acid synthase. In adipocytes, the extracts significantly reduced the mRNA expression of inflammation-related factors following LPS treatment. The activation of NF-κB p65 and ERK 1/2 was inhibited in extract-treated adipocytes. Moreover, treatment with extract #8 markedly reduced the cell population of the G2/M phase. Collectively, these results indicate that transgenic rice containing PPD may act as an obesity-reducing and/or -preventing agent.

Germinated Rice Seeds Improved Resveratrol Production to Suppress Adipogenic and Inflammatory Molecules in 3T3-L1 Adipocytes.

Obesity is a major risk factor for a variety of diseases and contributes to chronic inflammation. Resveratrol is a naturally occurring antioxidant that can reduce adipogenesis. In this study, the antiadipogenic and anti-inflammatory activities of resveratrol-enriched rice were investigated in 3T3-L1 adipocyte cells. Cotreatment of dexamethasone and isobutylmethylxanthin upregulated adipogenic transcription factors and signaling pathways. Subsequent treatment of adipocytes with rice seed extracts suppressed the differentiation of 3T3-L1 by downregulating adipogenic transcription factors (peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α) and signaling pathways (extracellular signal-regulated kinase 1/2 and protein kinase B Akt), this was especially observed in cells treated with germinated resveratrol-enriched rice seed extract (DJ526_5). DJ526_5 treatment also markedly reduced lipid accumulation in the cells and expression of adipogenic genes. Lipopolysaccharide (LPS)-induced inflammatory cytokines (prostaglandin-endoperoxide synthase 2 (COX-2), tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6) decreased in cells treated with DJ526_5. Collectively, DJ526_5 exerts antiadipogenic effects by suppressing the expression of adipogenesis transcription factors. Moreover, DJ526_5 ameliorates anti-inflammatory effects in 3T3-L1 adipocytes by inhibiting the activation of phosphorylation NF-κB p65 and ERK ½ (MAPK). These results highlight the potential of resveratrol-enriched rice as an alternative obesity-reducing and anti-inflammatory agent.

Inhibitory Effects of Polyphenol- and Flavonoid-Enriched Rice Seed Extract on Melanogenesis in Melan-a Cells via MAPK Signaling-Mediated MITF Downregulation.

Melanin production is an important process that prevents the host skin from harmful ultraviolet radiation; however, an overproduction of melanin results in skin diseases. In the present study, we determined the antioxidative and anti-melanogenic activities of polyphenol- and flavonoid-enriched rice seed extracts in melan-a cells. The polyphenol and flavonoid content of Hopum (HP) and Sebok (SB) rice seed extracts was measured. The antioxidant capacity was determined using the ABTS radical scavenging method. SB contained high amounts of polyphenols and flavonoids, which significantly increased antioxidative activity compared with HP. Various concentrations of these extracts were evaluated in a cytotoxicity using melan-a cells. At 100 µg/mL, there was no significant difference for all treatments compared with untreated cells. Therefore, 100 µg/mL was selected as a concentration for the further experiments. SB significantly suppressed the phosphorylation/activation of p-38 MAPK, increased the expression of phosphorylated ERK 1/2 and Akt, and downregulated the microphthalmia-associated transcription factor (MITF). This resulted in decreased levels of tyrosinase and tyrosinase-related protein-1 and -2. These results indicate the potential of polyphenol- and flavonoid-enriched rice seed as a treatment for hyperpigmentation.

Use of Germination to Enhance Resveratrol Content and Its Anti-Inflammatory Activity in Lipopolysaccharide-Stimulated RAW264.7 Cells.

Inflammation is triggered by a variety of danger signals and is now a worldwide concern. Resveratrol, a natural nonflavonoid polyphenol found in naturally consumed plants and foods, has a wide spectrum of bioactive potency. We successfully generated resveratrol-enriched rice by introducing the resveratrol biosynthesis gene into Dongjin rice. In this study, resveratrol- and piceid-enriched rice (DJ526) was investigated for its anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated RAW264.7 cells compared to normal rice (DJ). In addition, the 5-day-old germinated DJ526 (DJ526_5) was tested for its anti-inflammatory effects. The piceid and resveratrol amounts increased in DJ526_5 by germination. Treatment of LPS-stimulated RAW264.7 cells with resveratrol-enriched rice seed extracts (DJ526_0 and DJ526_5) significantly decreased the production of nitric oxide (NO) and the inflammatory mediator prostaglandin E2 (PGE2), downregulated proinflammatory gene expression, and inhibited nuclear factor kappa B (NF-κB) p65, p38 mitogen-activated protein kinase, and extracellular signal-regulated kinase 1/2 (ERK 1/2) phosphorylation. These findings demonstrated the anti-inflammatory mechanisms of resveratrol-enriched rice in LPS-stimulated RAW264.7 cells. Furthermore, resveratrol-enriched rice could be a potential source of anti-inflammatory agents.

Metabolite Profiling to Evaluate Metabolic Changes in Genetically Modified Protopanaxadiol-Enriched Rice.

Event DS rice producing protopanaxadiol (PPD) has been previously developed by inserting Panax ginseng dammarenediol-II synthase gene (PgDDS) and PPD synthase gene (CYP716A47). We performed a gas chromatography-mass spectrometry (GC-MS)-based metabolomics of the DS rice to identify metabolic alterations as the effects of genetic engineering by measuring the contents of 65 metabolites in seeds and 63 metabolites in leaves. Multivariate analysis and one-way analysis of variance between DS and non-genetically modified (GM) rice showed that DS rice accumulated fewer tocotrienols, tocopherols, and phytosterols than non-GM rice. These results may be due to competition for the same precursors because PPDs in DS rice are synthesized from the same precursors as those of phytosterols. In addition, multivariate analysis of metabolic data from rice leaves revealed that composition differed by growth stage rather than genetic modifications. Our results demonstrate the potential of metabolomics for identifying metabolic alterations in response to genetic modifications.

Effect of Ginseng Sapogenin Protopanaxadiol-Enriched Rice (DJ-PPD) on Immunomodulation.

Protopanaxadiol (PPD), a gut microbiome-induced ginseng metabolite, has positive immune effects. We previously reported the immune-boosting and anti-inflammatory effects of PPD-enricshed rice seed extracts in normal and inflammatory cell environments, respectively. In the present study, the immunomodulatory activity of PPD-enriched transgenic rice seed extract (DJ-PPD), which exhibited the highest immune-related activity among all available extracts, was compared with that of commercially synthesized 20s-PPD (S-PPD) and natural ginseng root extract (GE), in RAW264.7 cells. Compared with S-PPD and GE treatment, DJ-PPD treatment (i) significantly promoted NF-κB p65 and c-Jun N-terminal protein kinase (JNK) phosphorylation; (ii) upregulated IL-1ß, IL-6, COX-2, TLR-4, and TNF-α expression; (iii) and increased prostaglandin E2 (PGE2) production. However, there were no significant differences in the effects of the three treatments containing PPD-type sapogenin or saponins on nitric oxide (NO) production and phagocytic activity. In the inflammatory cell environment, DJ-PPD treatment markedly decreased the production of LPS-induced inflammatory factors, including NO and PGE2, as well as proinflammatory cytokine expression, by decreasing phosphorylated (p-)NF-κB p65, p-p38 MAPK, and p-JNK levels. Thus, DJ-PPD that does not require complex intestinal microbial processes to exert higher anti-inflammatory effects compared with S-PPD and GE. However, DJ-PPD exerted similar or higher immune-boosting effects (depending on inflammatory biomarkers) than S-PPD and GE. These findings indicate the potential of PPD-enriched transgenic rice as an alternative immunomodulatory agent.

Protopanaxadiol-Enriched Rice Extracts Suppressed Oxidative and Melanogenic Activities in Melan-a Cells.

Concerns about hyperpigmentation and skin appearance have led to increasing research into the prevention and altering of skin pigmentation. Natural compounds may be of interest in the search for skin-lightening actives. Protopanaxadiol (PPD), a gut microbiome-induced ginseng metabolite, has been reported to have anti-melanogenic effects. This study aimed to evaluate the antioxidative and anti-melanogenic effects of PPD-enriched rice seed extracts on melan-a cells. The antioxidant and cytotoxicity activities of the extracts were investigated in melan-a cells before measuring their responses to melanogenic activities. The extracts significantly enhanced the antioxidant potency compared with normal rice seed extract. PPD-enriched rice seed extracts (i) significantly downregulated microphthalmia-associated transcription factor, which led to a reduction in tyrosinase and tyrosinase-related protein-1 and -2, (ii) decrease in the cellular tyrosinase activity and melanin content, (iii) reduction in the number of melanin-containing cells, (iv) promotion of melanogenesis downregulators, phosphorylation of extracellular signal-regulated kinase 1/2 and protein kinase B, and (v) downregulation of the phosphorylated p38 mitogen-activated protein kinase and melanin synthesis. These results indicate the feasibility of PPD-enriched rice seed extracts as a novel agent for suppressing melanogenesis and controlling hyperpigmentation.

Inhibitory Effects of Protopanaxadiol-Producing Transgenic Rice Seed Extracts on RANKL-Induced Osteoclast Differentiation.

(1) Background: Osteoporosis is a disease in which bones are weakened and fractured easily because of various factors. It is mainly observed in elderly and postmenopausal women, and it continues to carry high economic costs in aging societies. Normal bone maintains a healthy state through a balanced process of osteoclast suppression and osteoblast activation; (2) Methods: In this study, osteoclast inhibition was induced by inhibiting osteoclast differentiation using ginseng protopanaxadiol-enriched rice (PPD-rice) seed extract. To analyze the effect of PPD-rice extract on the inhibition of osteoclast differentiation, bone marrow macrophages extracted from mice were treated with PPD-rice and Dongjin seed (non-transformed rice) extracts and analyzed for the inhibition of osteoclast differentiation; (3) Results: The results illustrated that PPD-rice extract reduced the transcription and translation of NFATc1, a modulator of osteoclast formation, decreased the mRNA expression of various osteoclast differentiation marker genes, and reduced osteoclast activity. Moreover, the bone resorptive activity of osteoclasts was diminished by PPD-rice extract on Osteo Assay plates; (4) Conclusions: Based on these results, PPD-rice extract is a useful candidate therapeutic agent for suppressing osteoclasts, an important component of osteoporosis, and it could be used as an ingredient in health supplements.

Transgenic Rice Seed Extracts Exert Immunomodulatory Effects by Modulating Immune-Related Biomarkers in RAW264.7 Macrophage Cells.

Protopanaxadiol (PPD), a native active triterpenoid present in Panax ginseng, has been reported to exert immune-related effects. We previously created PPD-producing transgenic rice by introducing the P. ginseng protopanaxadiol synthase and dammarenediol-II synthase genes into Dongjin rice. In the present study, the seeds of the T4 generation of this transgenic rice were tested for their immunomodulatory effects in RAW264.7 macrophage cells. Treatment with transgenic rice seed extract in RAW264.7 cells (i) significantly enhanced nitric oxide (NO) production in a dose-dependent manner without any cytotoxicity (up to 100 µg/mL), (ii) upregulated the expression of immune-related genes and increased production of the inflammation mediator prostaglandin E2 (PGE2), and (iii) activated nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) by promoting the phosphorylation of NF-κB p65, p38 MAPK, and c-Jun N-terminal protein kinase (JNK). In lipopolysaccharide (LPS)-treated RAW264.7 cells used to mimic the inflammation condition, treatment with transgenic rice seed extract significantly reduced NO production, proinflammatory cytokine expression, and PGE2 production, all of which are LPS-induced inflammation biomarkers, by inhibiting the phosphorylation of NF-κB p65, p38 MAPK, and JNK. Collectively, these results indicate that PPD-producing transgenic rice has immunomodulatory effects.

Enhanced Anti-Skin-Aging Activity of Yeast Extract-Treated Resveratrol Rice DJ526.

Resveratrol is a powerful antioxidant that defends against oxidative stress in cells but is not found in large quantities in plants. Resveratrol-enriched rice DJ526, which was developed as a functional crop, shows a diverse range of biological activities. Resveratrol production is measured as total resveratrol and its glycoside, piceid, which is mainly found in plant-derived resveratrol. In the present study, elicitation using yeast extract (YE), methyl jasmonate, and jasmonic acid increased resveratrol production in DJ526 rice seeds. DJ526 seeds elicited using 1 g/L (YE1) and 5 g/L yeast extract (YE5) showed enhanced resveratrol production and antioxidant activity. YE5-treated DJ526 seeds showed decreased melanin content by 46.1% and 37.0% compared with the negative control and DJ526 (non-elicitation), respectively. Both YE1 and YE5 efficiently improved the wound-healing activity by reducing the wound gap faster than in untreated cells, with a maximum rate of 60.2% at 24 h and complete closure at 48 h. YE1 and YE5 significantly decreased the levels of proinflammatory cytokine, TNF-α, and enhanced collagen synthesis in inflammatory cells. These findings indicate that YE-treated resveratrol rice DJ526 may improve resveratrol production and could be an active antiaging ingredient for cosmetic and skin therapy applications.

Resveratrol-enriched rice identical to original Dongjin rice variety with respect to major agronomic traits in different cultivation years and regions.

Resveratrol is synthesized by the catalysis of resveratrol synthases (RS) in a limited number of higher plants. Resveratrol shows potential health-promoting properties, including as an antioxidant and in preventing cardiovascular diseases. Recently, resveratrol-enriched rice has been produced as a novel source of resveratrol. This study aimed to investigate the major agronomic characteristics of resveratrol-enriched rice, Iksan526 (I526) and compared them with those of a nontransgenic and commercial rice variety, Dongjin (DJ). Transgene (RS) integration was confirmed using Southern blot analysis, and homologous recombination was achieved after digestion with the SacI restriction enzyme. The phenotypic traits of I526 grown in Iksan were similar to those grown in Milyang but not similar to those grown in Suwon. In Suwon, I526 had slightly earlier heading dates [i.e., number of days from sowing to heading) and shorter culm lengths. When I526 was treated with 0.4% Basta in the seedling stage, no significant difference was observed among all the agronomic traits compared with nontreated I526; particularly, the culm length, panicle length, number of panicles per hill, 1,000 grain weight of brown rice, and brown rice yield of the Basta-treated rice were similar to those of the nontreated I526, regardless of their cultivation region. The resveratrol content of I526 grown in Suwon and Milyang was increased by 18% and 37%, respectively, than that of I526 grown in the Iksan area. Therefore, DJ and I526 are not significantly different in terms of major agronomic traits depending on variety/year and variety/cultivation region. The results indicated that I526 has the potential to become a commercialized variety in the near future.

Enhancing Resveratrol Bioproduction and Anti-Melanogenic Activities through Elicitation in DJ526 Cell Suspension.

Resveratrol, a secondary plant metabolite, and its derivatives, including piceid, show several potential health-related biological activities. However, resveratrol production is uncommon in plants; thus, resveratrol-enriched rice (DJ526) is produced for its nutritional and therapeutic value. Here, a DJ526 cell suspension was treated with various elicitors to determine its resveratrol-production potential and elicit its biological activity. Treatments with most elicitors produced more piceid than resveratrol; as elicitation periods increased, the average piceid levels were 75-fold higher than resveratrol levels. This increase is associated with glycosylation during growth and development. The duration of exposure and concentrations of elicitors were crucial factors affecting resveratrol synthase expression. Of all the elicitors tested, jasmonic acid and methyl jasmonate (MeJA) were strong elicitors; they increased resveratrol production to ≤115.1 µg g-1 (total resveratrol and piceid content). Moreover, 5 µM of MeJA increased total resveratrol production by >96.4% relative to the control production. In addition, the extract of cell suspension treated with 5 µM of MeJA significantly reduced melanin content and cellular tyrosinase activity (24.2% and 21.5% relative to the control, respectively) in melan-a cells without disturbing cell viability. Overall, elicitation can enhance resveratrol production and elicit the biological activity of the compound, in this case, its anti-melanogenic activities, in DJ526 cell suspension.

Alteration of resveratrol-dependent glycosyltransferase activity by elicitation in DJ-526 rice.

Since the successful creation of DJ-526, a resveratrol-enriched rice cultivar, research has focused on resveratrol production because of its great potential in pharmaceutical applications. However, the utilization of resveratrol in DJ-526 is limited by glycosylation, which converts resveratrol to its glucoside (piceid), in a process driven by glycosyltransferase. The verification of resveratrol-dependent glycosyltransferase activity is an essential strategy for improving resveratrol production in DJ-526 rice. In this study, 27 candidate glycosyltransferases were evaluated in germinated seeds. Among the candidates, only R12 exhibited upregulation related to increased resveratrol and piceid content during seed germination, whereas various effects on the activity of glycosyltransferase were observed by the presence of a bio-elicitor. Yeast extract tended to enhance glycosyltransferase activity by seven candidates, and a specific peak for an unknown compound production was identified. Conversely, chitosan acted as a glycosyltransferase inhibitor. Our results suggested that R12 and R19 are the most relevant candidate resveratrol-dependent glycosyltransferases in DJ-526 seeds during germination and elicitation. Future research should assess the possibility of silencing these candidate genes in an effort to improve resveratrol levels in DJ-526 rice.

Effect of the Resveratrol Rice DJ526 on Longevity.

Resveratrol is the best-known chemical for extending the lifespan of various organisms. Extensive recent research has shown that resveratrol can extend the lifespan of single-celled organisms, but its effects on the extension of animal lifespans are marginal. Despite the limited efficacy of pure resveratrol, resveratrol with the endogenous property of the DJ rice in the resveratrol rice DJ526 previously showed profound health benefits. Here, we report that the resveratrol rice DJ526 markedly extended the lifespan of the fruit fly Drosophila melanogaster by as much as 41.4% compared to that of the control. The resveratrol rice DJ526 also improved age-related symptoms such as locomotive deterioration, body weight gain, eye degeneration and neurodegeneration in D. melanogaster upon aging. This result shows the most significantly improved lifespan in animal experiments to date, meaning that the resveratrol rice DJ526 will assist in the development of a therapeutic agent for longevity or addressing age-related degeneration.

Genetically modified rice produces ginsenoside aglycone (protopanaxadiol).

MAIN CONCLUSION: Protopanaxadiol is dammarane-type tetracyclic triterpene sapogenin found in ginseng and has a high medicinal values. We successfully constructed transgenic rice producing protopanaxadiol by introducing the ginseng PgDDS and CYP716A47 genes in this crop plant. Protopanaxadiol (PPD), an aglycone of ginsenosides, possesses pleiotropic anticarcinogenesis activities in many cancers. Here, we constructed transgenic rice overexpressing the Panax ginseng dammarenediol-II synthase gene (PgDDS) and protopanaxadiol synthase gene (CYP716A47) driven by a rice endosperm-specific α-globulin promoter. Among more than 50 independent lines, five transgenic lines were selected. The introduction of the genes in the T1 generation of the transgenic lines was confirmed by genomic PCR. The expression of the introduced genes in T2 seeds was confirmed by qPCR. Methanol extracts of transgenic rice grains were analyzed by LC/MS to detect the production of PPD and dammarenediol-II (DD). The production of both PPD and DD was identified not only by comparing the retention times but also mass fraction patterns of authentic PPD and DD standards. The mean concentrations of PPD and DD in rice grains were 16.4 and 4.5 µg/g dry weight, respectively. The invention of genetically engineered rice grains producing PPD and DD can be applied to rice breeding to reinforce new medicinal values.

The Resveratrol Rice DJ526 Callus Significantly Increases the Lifespan of Drosophila (Resveratrol Rice DJ526 Callus for Longevity).

Resveratrol has gained widespread scientific attention due to its ability to significantly extend the lifespan of yeast. However, research on the efficacy of resveratrol on lifespan extension has yielded mixed results in animal studies, making resveratrol a contentious subject. In our previous work, we reported that transgenic resveratrol rice DJ526 showed unusual health benefits beyond expectations. In this work, we established a callus culture of resveratrol rice DJ526, which contains 180 times more resveratrol than the grain, and found that resveratrol rice callus significantly extended the median lifespan of Drosophila melanogaster by up to 50% compared to the control. The resveratrol rice callus also ameliorated age-dependent symptoms, including locomotive deterioration, body weight gain, eye degeneration, and neurodegeneration of D. melanogaster with age progression. Considering that resveratrol is the most preferred antiaging compound due to its superior safety and proven mechanism against many serious adult diseases, the outstanding efficacy of resveratrol on the longevity of wild-type animals could cast a light on the development of antiaging therapeutic agents.

Biogenesis of chloroplast outer envelope membrane proteins.

Most organisms on Earth use glucose, a photosynthetic product, as energy source. The chloroplast, the home of photosynthesis, is the most representative and characteristic organelle in plants and is enclosed by the outer envelope and inner envelope membranes. The chloroplast biogenesis and unique functions are very closely associated with proteins in the two envelope membranes of the chloroplast. Especially, the chloroplast outer envelope membrane proteins have important roles in signal transduction, protein import, lipid biosynthesis and remodeling, exchange of ions and numerous metabolites, plastid division, movement, and host defense. Therefore, biogenesis of these membrane proteins of chloroplast outer envelope membrane is very important for biogenesis of the entire chloroplast proteome as well as plant development. Most proteins among the outer envelope membrane proteins are encoded by the nuclear genome and are post-translationally targeted to the chloroplast outer envelope membrane. In this process, cytoplasmic receptor and import machineries are required for efficient and correct targeting of these membrane proteins. In this review, we have summarized recent advances on the sorting, targeting, and insertion mechanisms of the outer envelope membrane proteins of chloroplasts and also provide future direction of the study on these topics.

Corrigendum to "Resveratrol-Enriched Rice Attenuates UVB-ROS-Induced Skin Aging via Downregulation of Inflammatory Cascades".

[This corrects the article DOI: 10.1155/2017/8379539.].

Genetically Engineered Resveratrol-Enriched Rice Inhibits Neuroinflammation in Lipopolysaccharide-Activated BV2 Microglia Via Downregulating Mitogen-Activated Protein Kinase-Nuclear Factor Kappa B Signaling Pathway.

Resveratrol, a natural stilbenoid, is produced by several plants, especially grape vines. Its strong potency against obesity, metabolic disorders, vascular disease, inflammation, and various cancers has already been reported. Large amounts of wine or grapes need to be consumed to obtain the amount of resveratrol required for biological activity. Pure resveratrol at concentrations as low as 10 µM induces cytotoxicity to normal cells. To overcome these limitations, we prepared genetically modified resveratrol-enriched rice (RR). We previously reported the strong antiaging potential of RR against ultraviolet B/reactive oxygen species-induced toxicity in normal human dermal fibroblasts (NHDF). As aging is characterized by neuroinflammation and neurodegeneration, we further evaluated the role of RR against LPS-induced neuroinflammation. RR inhibited nitric oxide production and the expression of inflammatory proteins such as iNOS and COX-2. RR significantly modulated mitogen-activated protein kinase signaling, activator protein AP-1 signaling, and nuclear factor kappa B (NF-κB) mediated transcription of inflammatory proteins via inhibition of NF-κB translocation, IkB phosphorylation, and proinflammatory cytokine productions such as interleukin IL-6, IL-1ß, tumor necrosis factor alpha (TNF-α), and prostaglandin E2 (PGE2). These findings show that the strong antineuroinflammatory effects of RR can be beneficial for aging-mediated neurodegenerative conditions as well as disorders of the central nervous system caused by neuroinflammation.

Resveratrol-Enriched Rice Attenuates UVB-ROS-Induced Skin Aging via Downregulation of Inflammatory Cascades.

The skin is the outermost protective barrier between the internal and external environments in humans. Chronic exposure to ultraviolet (UV) radiation is a major cause of skin aging. UVB radiation penetrates the skin and induces ROS production that activates three major skin aging cascades: matrix metalloproteinase- (MMP-) 1-mediated aging; MAPK-AP-1/NF-κB-TNF-α/IL-6, iNOS, and COX-2-mediated inflammation-induced aging; and p53-Bax-cleaved caspase-3-cytochrome C-mediated apoptosis-induced aging. These mechanisms are collectively responsible for the wrinkling and photoaging characteristic of UVB-induced skin aging. There is an urgent requirement for a treatment that not only controls these pathways to prevent skin aging but also avoids the adverse effects often encountered when applying bioactive compounds in concentrated doses. In this study, we investigated the efficacy of genetically modified normal edible rice (NR) that produces the antiaging compound resveratrol (R) as a treatment for skin aging. This resveratrol-enriched rice (RR) overcomes the drawbacks of R and enhances its antiaging potential by controlling the abovementioned three major pathways of skin aging. RR does not exhibit the toxicity of R alone and promisingly downregulates the pathways underlying UVB-ROS-induced skin aging. These findings advocate the use of RR as a nutraceutical for antiaging purposes.