Oral Administration of Euonymus alatus Leaf Extract Ameliorates Alzheimer's Disease Phenotypes in 5xFAD Transgenic Mice.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease and is frequently characterized by progressive and irreversible impairment of cognitive functions. However, its etiology remains poorly understood, limiting therapeutic interventions. Our previous study showed that the ethanol extract of Euonymus alatus leaves (EA) positively affected scopolamine-induced hypomnesia in the normal mouse model by promoting nuclear factor E2-related factor 2 (Nrf2) activation. Herein, we examined whether EA administration could ameliorate major AD phenotypes that are manifested in 5xFAD transgenic mice. Two-month-old mice were orally administered with EA at a dose of 50, 100, or 150 mg/kg body weight/day thrice a week for 14 weeks. We observed that EA administration improved behavioral deficits as assessed by the passive avoidance, Morris water maze, and Y-maze tasks; decreased the plasma levels of pro-inflammatory cytokines, including TNFα and IL-1ß; decreased the protein expression levels of inflammatory mediators in the hippocampus; and attenuated histological damage and amyloid beta plaques in the hippocampal region of 5xFAD mouse brain. Interestingly, our data demonstrated that the effectiveness was partially attributed to quercetin, which was noted to be a component of EA. Hence, these findings suggest that a long-term administration of EA could alleviate AD symptoms and delay its progression.

Quercetin-Induced Glutathione Depletion Sensitizes Colorectal Cancer Cells to Oxaliplatin.

Quercetin is an antioxidant phytochemical which belongs to the natural flavonoids group. Recently, the compound has been reported to inhibit glutathione reductase responsible for replenishing reduced forms of glutathione and thus leads to glutathione depletion, triggering cell death. In this study, we examined if quercetin sensitizes tumors to oxaliplatin by inhibiting glutathione reductase activity in human colorectal cancer cells, and thereby facilitates apoptotic cell death. A combined treatment with quercetin and oxaliplatin was found to synergistically inhibit glutathione reductase activity, lower intracellular glutathione level, increase reactive oxygen species production, and reduce cell viability, compared to treatment with oxaliplatin alone in human colorectal HCT116 cancer cells. Furthermore, the incorporation of sulforaphane, recognized for its ability to scavenge glutathione, in combination with quercetin and oxaliplatin, substantially suppressed tumor growth in an HCT116 xenograft mouse model. These findings suggest that the depletion of intracellular glutathione by quercetin and sulforaphane could strengthen the anti-cancer efficacy of oxaliplatin.

Long-Term Administration of Vespa velutina nigrithorax Venom Ameliorates Alzheimer's Phenotypes in 5xFAD Transgenic Mice.

Alzheimer's disease (AD), the most prevalent neurodegenerative disease, is characterized by progressive and irreversible impairment of cognitive functions. However, its etiology is poorly understood, and therapeutic interventions are limited. Our preliminary study revealed that wasp venom (WV) from Vespa velutina nigrithorax can prevent lipopolysaccharide-induced inflammatory signaling, which is strongly implicated in AD pathogenesis. Therefore, we examined whether WV administration can ameliorate major AD phenotypes in the 5xFAD transgenic mouse model. Adult 5xFAD transgenic mice (6.5 months of age) were treated with WV by intraperitoneal injection at 250 or 400 µg/kg body weight once weekly for 14 consecutive weeks. This administration regimen improved procedural, spatial, and working memory deficits as assessed by the passive avoidance, Morris water maze, and Y-maze tasks, respectively. It also attenuated histological damage and amyloid-beta plaque formation in the hippocampal region and decreased expression levels of pro-inflammatory factors in the hippocampus and cerebrum, while it reduced oxidative stress markers (malondialdehyde in the brain and liver and 8-hydroxy-2'-deoxyguanosine in the plasma). Overall, these findings suggest that long-term administration of WV may alleviate AD-related symptoms and pathological phenotypes.

Luteolin Synergistically Enhances Antitumor Activity of Oxaliplatin in Colorectal Carcinoma via AMPK Inhibition.

Luteolin is a naturally-occurring polyphenolic compound that is known to have antioxidative and antitumor activities in vitro. This study aimed to examine the in vivo anticancer efficacy of luteolin in conjunction with oxaliplatin treatment using a colorectal carcinoma xenograft mouse model. HCT116 human colorectal carcinoma cells were subcutaneously implanted into BALB/c nude mice, followed by the intraperitoneal administration of luteolin at a dose of 50 mg/kg body weight (BW)/day with or without oxaliplatin at a dose of 10 mg/kg BW/day three times per week for a total of 3 weeks. The combined luteolin and oxaliplatin treatment resulted in the synergistic suppression of the growth of HCT116 xenograft tumors when compared to treatment with luteolin or oxaliplatin alone. In addition, the combined treatment significantly increased the expression of cleaved PARP and p53 in the xenograft tumors compared with the vehicle control, but only marginally affected the level of heme oxygenase-1 (HO-1). These results indicated that luteolin treatment retarded oxaliplatin-induced tumor growth by facilitating apoptotic cell death and inhibiting HO-1-mediated cytoprotection. Therefore, these findings suggest the synergistic potential of dietary luteolin in conjunction with conventional chemotherapy for the treatment of colorectal cancer.

Wasp Venom Ameliorates Scopolamine-Induced Learning and Memory Impairment in Mice.

This study investigated the effects of wasp venom (WV) from the yellow-legged hornet, Vespa velutina, on scopolamine (SCO)-induced memory deficits in mice, as well as the antioxidant activity in HT22 murine hippocampal neuronal cells in parallel comparison with bee venom (BV). The WV was collected from the venom sac, freeze-dried. Both venoms exhibited free radical scavenging capabilities in a concentration-dependent manner. In addition, the venom treatment enhanced cell viability at the concentrations of ≤40 µg/mL of WV and ≤4 µg/mL of BV in glutamate-treated HT22 cells, and increased the transcriptional activity of the antioxidant response element (ARE), a cis-acting enhancer which regulates the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)-downstream antioxidant enzymes. Concurrently, WV at 20 µg/mL significantly increased the expression of a key antioxidant enzyme heme oxygenase 1 (HO-1) in HT22 cells despite no significant changes observed in the nuclear level of Nrf2. Furthermore, the intraperitoneal administration of WV to SCO-treated mice at doses ranged from 250 to 500 µg/kg body weight ameliorated memory impairment behavior, reduced histological injury in the hippocampal region, and reduced oxidative stress biomarkers in the brain and blood of SCO-treated mice. Our findings demonstrate that WV possess the potential to improve learning and memory deficit in vivo while further study is needed for the proper dose and safety measures and clinical effectiveness.

Anti-neuroinflammatory activity of 6,7-dihydroxy-2,4-dimethoxy phenanthrene isolated from Dioscorea batatas Decne partly through suppressing the p38 MAPK/NF-κB pathway in BV2 microglial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Dioscorea batatas Decne (called Chinses yam) widely distributed in East Asian countries including China, Japan, Korea and Taiwan has long been used in oriental folk medicine owing to its tonic, antitussive, expectorant and anti-ulcerative effects. It has been reported to have anti-inflammatory, antioxidative, cholesterol-lowering, anticholinesterase, growth hormone-releasing, antifungal and immune cell-stimulating activities. AIM OF THE STUDY: Neuroinflammation caused by activated microglia contributes to neuronal dysfunction and neurodegeneration. In the present study, the anti-neuroinflammatory activity of 6,7-dihydroxy-2,4-dimethoxy phenanthrene (DHDMP), a phenanthrene compound isolated from Dioscorea batatas Decne, was examined in microglial and neuronal cells. MATERIALS AND METHODS: A natural phenanthrene compound, DHDMP, was isolated from the peel of Dioscorea batatas Decne. The anti-neuroinflammatory capability of the compound was examined using the co-culture system of BV2 murine microglial and HT22 murine neuronal cell lines. The expression levels of inflammatory mediators and cytoprotective proteins in the cells were quantified by enzyme-linked immunosorbent assay and Western blot analysis. RESULTS: DHDMP at the concentrations of ≤1 µg/mL did not exhibit a cytotoxic effect for BV2 and HT22 cells. Rather DHDMP effectively restored the growth rate of HT22 cells, which was reduced by co-culture with lipopolysaccharide (LPS)-treated BV2 cells. DHDMP significantly decreased the production of proinflammatory mediators, such as nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 in BV2 cells. Moreover, DHDMP strongly inhibited the nuclear translocation of nuclear factor κB (NF-κB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in BV2 cells. The compound did not affect the levels and phosphorylation of ERK and JNK. Concurrently, DHDMP increased the expression of heme oxygenase-1 (HO-1), an inducible cytoprotective enzyme, in HT22 cells. CONCLUSIONS: Our findings indicate that DHDMP effectively dampened LPS-mediated inflammatory responses in BV2 microglial cells by suppressing transcriptional activity of NF-κB and its downstream mediators and contributed to HT22 neuronal cell survival. This study provides insight into the therapeutic potential of DHDMP for inflammation-related neurological diseases.

Dietary supplementation with Ceriporia lacerata improves learning and memory in a scopolamine-induced amnesia mouse model.

Ceriporia lacerata (CL) is a species of white rot fungi. In this study, we have examined the beneficial effect of CL on scopolamine-induced memory impairment in mice. A freeze-dried CL mycelial culture broth was dissolved and orally administered to scopolamine-treated C57BL/6J mice followed by behavioral tests using the Y-maze, passive avoidance, and Morris water maze tasks. CL administration at a daily dose of 200 mg/kg body weight resulted in restoration of exploration reduction and improvement of associative and spatial learning and memory impairment in scopolamine-treated mice. Concomitantly, heme oxygenase-1 was highly expressed in the hippocampal region of CL-administered mice. Moreover, the ethanolic extract of CL significantly increased the transcriptional activity of antioxidant response element and attenuated the glutamate-induced cytotoxicity in HT22 mouse hippocampal neuronal cells. These findings suggest that the CL intake can confer a beneficial effect on learning and memory presumably through protecting hippocampal neuronal cells from oxidative stress-induced damage. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-021-00945-5.

Anti-Inflammatory Effect of Wasp Venom in BV-2 Microglial Cells in Comparison with Bee Venom.

The aim of this study was to compare the anti-inflammatory effect of wasp venom (WV) from the yellow-legged hornet (Vespa velutina) with that of bee venom (BV) on BV-2 murine microglial cells. WV was collected from the venom sac, freeze-dried, and used for in vitro examinations. WV and BV were non-toxic to BV-2 cells at concentrations of 160 and 12 µg/mL or lower, respectively. Treatment with WV reduced the secretion of nitric oxide and proinflammatory cytokines, including interleukin-6 and tumor necrosis factor alpha, from BV-2 cells activated by lipopolysaccharide (LPS). Western blot analysis revealed that WV and BV decreased the expression levels of inflammation markers, including inducible nitric oxide synthase and cyclooxygenase-2. In addition, WV decreased the nuclear translocation of nuclear factor κB (NF-κB), which is a key transcription factor in the regulation of cellular inflammatory response. Cumulatively, the results demonstrated that WV inhibited LPS-induced neuroinflammation in microglial cells by suppressing the NF-κB-mediated signaling pathway, which warrants further studies to confirm its therapeutic potential for neurodegenerative diseases.

Fermented Soy Products: Beneficial Potential in Neurodegenerative Diseases.

Fermented soybean products, such as cheonggukjang (Japanese natto), doenjang (soy paste), ganjang (soy sauce), and douchi, are widely consumed in East Asian countries and are major sources of bioactive compounds. The fermentation of cooked soybean with bacteria (Bacillus spp.) and fungi (Aspergillus spp. and Rhizopus spp.) produces a variety of novel compounds, most of which possess health benefits. This review is focused on the preventive and ameliorative potential of fermented soy foods and their components to manage neurodegenerative diseases, including Alzheimer's and Parkinson's diseases.

Comparison of Morphological and Physicochemical Properties of a Floury Rice Variety upon Pre-Harvest Sprouting.

Pre-harvest sprouting (PHS) severely reduces rice grain yield, significantly affects grain quality, and leads to substantial economic loss. In this study, we aimed to characterize the physicochemical properties and processing quality of the Garumi 2 flour rice variety under PHS conditions and compare them with those of the Seolgaeng, Hangaru, Shingil, and Ilpum rice varieties and the Keumkang wheat variety. Analysis of the molecular structure of starch revealed uniform starch granules, increased proportions of short-chain amylopectin in DP 6-12 (51.0-55.3%), and enhanced crystallinity (30.7-35.7%) in rice varieties for flour compared with the Ilpum cooking rice variety. PHS significantly altered the starch structure and gelatinization properties of Garumi 2. It also caused surface pitting and roughness in Garumi 2 starch granules and decreased their crystallinity. Collectively, the findings of this study provide important novel insights into the effects of PHS on the physicochemical properties of Garumi 2 floury rice for flour.

Oral administration of hydrolyzed red ginseng extract improves learning and memory capability of scopolamine-treated C57BL/6J mice via upregulation of Nrf2-mediated antioxidant mechanism.

BACKGROUND: Korean ginseng (Panax ginseng Meyer) contains a variety of ginsenosides that can be metabolized to a biologically active substance, compound K. Previous research showed that compound K could be enriched in the red ginseng extract (RGE) after hydrolysis by pectinase. The current study investigated whether the enzymatically hydrolyzed red ginseng extract (HRGE) containing a notable level of compound K has cognitive improving and neuroprotective effects. METHODS: A scopolamine-induced hypomnesic mouse model was subjected to behavioral tasks, such as the Y-maze, passive avoidance, and the Morris water maze tests. After sacrificing the mice, the brains were collected, histologically examined (hematoxylin and eosin staining), and the expressions of antioxidant proteins analyzed by western blot. RESULTS: Behavioral assessment indicated that the oral administration of HRGE at a dosage of 300 mg/kg body weight reversed scopolamine-induced learning and memory deficits. Histological examination demonstrated that the hippocampal damage observed in scopolamine-treated mouse brains was reduced by HRGE administration. In addition, HRGE administration increased the expression of nuclear-factor-E2-related factor 2 and its downstream antioxidant enzymes NAD(P)H:quinone oxidoreductase and heme oxygenase-1 in hippocampal tissue homogenates. An in vitro assay using HT22 mouse hippocampal neuronal cells demonstrated that HRGE treatment attenuated glutamate-induced cytotoxicity by decreasing the intracellular levels of reactive oxygen species. CONCLUSION: These findings suggest that HRGE administration can effectively alleviate hippocampus-mediated cognitive impairment, possibly through cytoprotective mechanisms, preventing oxidative-stress-induced neuronal cell death via the upregulation of phase 2 antioxidant molecules.

In Vivo Anti-inflammatory Potential of Viscozyme®-Treated Jujube Fruit.

The fruit of Ziziphus jujuba, commonly called jujube, has long been consumed for its health benefits. The aim of this study was to examine the protective effect of dietary supplementation of enzymatically hydrolyzed jujube against lung inflammation in mice. The macerated flesh of jujube was extracted with aqueous ethanol before and after Viscozyme treatment. The extract of enzyme-treated jujube, called herein hydrolyzed jujube extract (HJE), contained higher levels of quercetin, total phenolics, and flavonoids, and exhibited more effective radical-scavenging abilities in comparison to non-hydrolyzed jujube extract (NHJE). HJE treatment decreased production of inflammation-associated molecules, including nitric oxide and pro-inflammatory cytokines from activated Raw 264.7 or differentiated THP-1 cells. HJE treatment also reduced expression of nuclear factor-κB and its downstream proteins in A549 human lung epithelial cells. Moreover, oral supplementation of 1.5 g of HJE per kg of body weight (BW) attenuated histological lung damage, decreased plasma cytokines, and inhibited expression of inflammatory proteins and oxidative stress mediators in the lungs of mice exposed to benzo(a)pyrene at 50 mg/kg BW. Expression levels of antioxidant and cytoprotective factors, such as nuclear factor erythroid-derived 2-related factor 2 and heme oxygenase-1, were increased in lung and liver tissues from mice treated with HJE, compared to mice fed NHJE. These findings indicate that dietary HJE can reduce benzo(a)pyrene-induced lung inflammation by inhibiting cytokine release from macrophages and promoting antioxidant defenses in vivo.

Inhibitory Effect of Steamed Soybean Wastewater Against DSS-Induced Intestinal Inflammation in Mice.

This study was performed to examine the beneficial potential of steamed soybean wastewater (SSW), which is generated during the manufacture of fermented soybean products and usually discarded as a by-product. The SSW was found to contain considerable amounts of isoflavones and had concentration-dependent radical scavenging capabilities. Moreover, oral administration of SSW effectively prevented colonic damage induced by dextran sulfate sodium (DSS), based on improvement of morphological and histological features, reduction of oxidative stress indicators, suppression of proinflammatory cytokine production, downregulation of inflammatory marker expression in the colonic tissue, and inhibition of the inflammatory activation of macrophages. It suggests that SSW could prevent intestinal inflammation in humans, although its efficacy should be verified through careful study design in humans. These findings have implications for enhancement of the value-added of SSW and for reduction of wastewater treatment costs incurred by the food industry.

Neuroprotective Effects of Euonymus alatus Extract on Scopolamine-Induced Memory Deficits in Mice.

Euonymus alatus is considered to elicit various beneficial effects against cancer, hyperglycemia, menstrual discomfort, diabetic complications, and detoxification. The young leaves of this plant are exploited as food and also utilized for traditional medicine in East Asian countries, including Korea and China. Our preliminary study demonstrated that ethanolic extract from the Euonymus alatus leaf (EAE) exhibited the strongest antioxidant enzyme-inducing activity among more than 100 kinds of edible tree leaf extracts. This study investigated whether EAE could attenuate the cognitive deficits caused by oxidative stress in mice. Oral intubation of EAE at 100 mg/kg bw or higher resulted in significant improvements to the memory and behavioral impairment induced via i.p. injection of scopolamine. Furthermore, EAE enhanced the expression levels of hippocampal neurotrophic factors such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor in mice, activated the Nrf2, and the downstream heme oxygenase-1 (HO-1) a quintessential antioxidant enzyme. As rutin (quercetin-3-O-rutinose) was abundantly present in EAE and free quercetin was able to induce defensive antioxidant enzymes in an Nrf2-dependent manner, our findings suggested that quercetin derived from rutin via the intestinal microflora played a significant role in the protection of the mouse hippocampus from scopolamine-induced damage through BDNF-mediated Nrf2 activation, thereby dampening cognitive decline.

Potential health benefits of phenolic compounds in grape processing by-products.

Prevention emerges as a powerful approach in minimizing the risk of deleterious lifestyle diseases because therapies do not necessarily guarantee a permanent cure. Accordingly, consumers' growing preference for natural and health-promoting dietary options that are rich in antioxidants has become widespread. Grape (Vitis vinifera) is an antioxidant-rich fruit extensively grown for fresh or processed consumption. The long-term consumption of its polyphenolic antioxidants may promote multiple health benefits. However, grape pomace (GP), consisting of peel, seed, stem, and pulp, is discarded during grape processing, including juice extraction and winemaking, despite its substantial antioxidant content. Polyphenolic extraction techniques have been widely explored to date, but the consolidation of reported physiological impacts of GP-derived polyphenolic constituents is limited. Thus, this review highlights current studies of the potential applications of GP extract in disease prevention and treatment, emphasizing the major influence of polyphenolic compositions and origins of different grape varieties.

Carbon Monoxide Partially Mediates Protective Effect of Resveratrol Against UVB-Induced Oxidative Stress in Human Keratinocytes.

Based on the antioxidative effect of resveratrol (RES) in mitigating reactive oxygen species (ROS) production through the induction of nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxigenase-1 (HO-1) signaling pathway, we investigated whether the protective activity of RES against ROS-mediated cytotoxicity is mediated by intracellular carbon monoxide (CO), a product of HO-1 activity, in ultraviolet B (UVB)-irradiated human keratinocyte HaCaT cells. The cells were exposed to UVB radiation following treatment with RES and/or CO-releasing molecule-2 (CORM-2). RES and/or CORM-2 upregulated HO-1 protein expression, accompanied by a gradual reduction of UVB-induced intracellular ROS levels. CORM-2 reduced intracellular ROS in the presence of tin protoporphyrin IX, an HO-1 inhibitor, indicating that the cytoprotection observed was mediated by intracellular CO and not by HO-1 itself. Moreover, CORM-2 decreased RES-stimulated mitochondrial quantity and respiration and increased the cytosolic protein expressions of radical-scavenging superoxide dismutases, SOD1 and SOD2. Taken together, our observations suggest that RES and intracellular CO act independently, at least partly, in attenuating cellular oxidative stress by promoting antioxidant enzyme expressions and inhibiting mitochondrial respiration in UVB-exposed keratinocytes.

Improvement of cognitive function by Gochujang supplemented with tomato paste in a mouse model.

Gochujang, a traditional Korean hot sauce, was prepared with a variety of antioxidant-rich supplements to improve its bioactive functions and preference by pungency-sensitive people. Among the tested ingredients, tomato paste exhibited the strongest antioxidant and neuroprotective activities when added as a supplement to traditional gochujang. Furthermore, oral administration of gochujang prepared with tomato paste to mice significantly improved cognitive function compared to original gochujang. As gochujang supplemented with tomato paste was found to contain an appreciable amount of lycopene with neuroprotective activity, it is most likely that the neuroprotective activity and cognitive improvement by the product was partially attributable to cis-lycopene, a highly bioavailable form converted from trans-lycopene during the manufacturing process of the product. However, a further study is required to verify the precise underlying mechanism of action.

Inhibitory effects of compounds isolated from Dioscorea batatas Decne peel on particulate matter-induced pulmonary injury in mice.

Particulate matter 2.5 (PM2.5), with an aerodynamic diameter of ≤2.5 µm, is the primary air pollutant that plays a key role associated with lung injury produced by loss of vascular barrier integrity. Dioscorea batatas Decne (Chinese yam), a perennial plant belonging to Dioscoreaceae family, is widely cultivated in tropical and subtropical regions across Asia. Both aerial parts and root of D. batatas are consumed for nutritional and medicinal purposes. The aim of this study was to (1) identify the bioactive compounds present in D. batatas peel which may be responsible for inhibition of PM2.5-induced pulmonary inflammation in mice and (2) examine in vitro mechanisms underlying the observed effects of these compounds on mouse lung microvascular endothelial cells. The measured parameters include permeability, leukocyte migration, proinflammatory protein activation, reactive oxygen species (ROS) generation, and histology. Two phenanthrene compounds, 2,7-dihydroxy-4,6-dimethoxyphenanthrene (1) and 6,7-dihydroxy-2,4-dimethoxyphenanthrene (2) were isolated from D. batatas peels. Both these phenanthrene compounds exhibited significant scavenging activity against PM2.5-induced ROS and inhibited ROS-induced activation of p38 mitogen-activated protein kinase. In addition, enhancement of Akt pathway, involved in the maintenance of endothelial integrity, was noted. These phenanthrene compounds also reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid obtained from PM2.5-induced lung tissues. Evidence thus indicates that phenanthrene compounds derived from D. batatas may exhibit protective effects against PM2.5-induced inflammatory lung injury and vascular hyperpermeability in mice.

Grape Peel Extract and Resveratrol Inhibit Wrinkle Formation in Mice Model Through Activation of Nrf2/HO-1 Signaling Pathway.

Considering the anti-photoaging effect of antioxidant compounds, we investigated the protective capacity of grape peel extract (GPE) and resveratrol on ultraviolet (UV)-induced skin wrinkle formation. Total phenolic, total anthocyanin, and total flavonoid content in GPE prepared from peel of Campbell Early variety were 23.96 ± 0.09, 3.27 ± 0.40, and 1.24 ± 0.09 mg/g dry weight, respectively. Additionally, trans-resveratrol and piceid content of the resulting GPE were 117.14 ± 19.97 and 85.23 ± 8.89 µg/g dry weight, respectively. Oral administration of either 2 g GPE or 2 mg resveratrol per kg body weight in mice attenuated UVB-induced epidermal thickening (the thickness was reduced by about 63% and 55% with GPE and resveratrol consumption prior to exposure to UVB, respectively, compared to only UVB-treated condition) and had marginally protective effect on wrinkle formation of skin exposed to UVB. As introduction of either GPE or resveratrol induced Nrf2-dependent antioxidant enzymes including heme oxygenase-1 (HO-1) in liver and skin as well as inhibited metalloproteinases, it is highly probable that the extract or resveratrol mitigated UVB-induced photoaging through activation of Nrf2/HO-1 signaling pathway. PRACTICAL APPLICATION: This study proved that resveratrol and the extract of grape peel, a common by-product of grape juice processing, provide effective protection from UV-induced skin wrinkle formation. Therefore, grape peel extract, which contains an appreciable amount of bioactive compound resveratrol, can be utilized as functional food ingredient for the manufacture of inner beauty products.