The Preparation, Functional Properties, and Application of Food-Derived Antioxidants and Anti-Inflammatory Agents.

This Special Issue of Foods titled, "The Preparation, Functional Properties, and Application of Food-Derived Antioxidants and Anti-inflammatory Agents," has unveiled a fascinating panorama of the multifaceted ways food can contribute to our well-being [...].

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.

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.

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.

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.

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.

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.

Luteolin Shifts Oxaliplatin-Induced Cell Cycle Arrest at G0/G1 to Apoptosis in HCT116 Human Colorectal Carcinoma Cells.

Certain antioxidative flavonoids are known to activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates cellular antioxidants and detoxifying response and is reportedly highly activated in many types of cancers. Few studies on the potential undesired effects of flavonoid intake during chemotherapy have been conducted, yet Nrf2 activators could favor cancer cell survival by attenuating chemotherapeutic efficiency. This study aimed to examine if luteolin, an Nrf2 activator, hinders chemotherapeutic activity of oxaliplatin, a potent anticancer agent for colorectal cancer, in HCT116 cells. Luteolin treatment strongly increased the transcriptional activity of the antioxidant response element in HCT116 cells and induced the protein expression of heme oxygenase-1, which were indicative of its Nrf2-inducing potential. Intriguingly, 25 µM luteolin reduced cell viability through apoptotic induction, which was intensified in p53-expressing cells while 1 µM oxaliplatin caused cell cycle arrest at G0/G1-phase via the p53/p21-dependent mechanism. Moreover, luteolin treatment was found to reduce oxaliplatin-treated p53-null cell viability and colony counts further, thereby demonstrating an additional effect of luteolin in the killing of human colorectal tumor HCT116 cells not expressing functional p53 protein. The findings suggest that luteolin can induce p53-mediated apoptosis regardless of oxaliplatin treatment and may eliminate oxaliplatin-resistant p53-null colorectal cells.

Glyceollins Modulate Tumor Development and Growth in a Mouse Xenograft Model of Human Colon Cancer in a p53-Dependent Manner.

Glyceollins are soybean-derived phytoalexins that induce the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling pathway, which is involved in the detoxification of carcinogens and the removal of reactive oxygen species (ROS). Recent studies, however, have indicated that Nrf2 induction stimulates the development of pre-existing tumors and confers resistance to chemotherapy by elevating drug metabolism and by efficient scavenging of ROS produced by the Warburg effect, which is regulated, in turn, by the p53 tumor suppressor. This study, therefore, aimed at examining whether glyceollins could accelerate tumor growth in the presence of active p53, using a xenograft BALB/c nude mouse model transplanted subcutaneously with p53 wild-type and p53 null HCT116 human colon cancer cells. Glyceollins were orally administered at a dose of either 1 or 4 mg/kg body weight after xenografting HCT116 cells, and tumor growth and volume were monitored for 2 weeks. A high dose of glyceollins resulted in a significant increase in the average volume of p53 wild-type HCT116 xenografts, but not of p53 null HCT116 xenografts. However, a low dose of glyceollins had no effect on the tumor growth regardless of p53 presence. Interestingly, antioxidant enzymes, including heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase, were prominently induced by glyceollins in p53 wild-type xenografts, compared with p53 null xenografts. These results suggest that a high dose of glyceollins possibly promotes the growth of p53 wild-type colon cancer through activation of the Nrf2-mediated signaling pathway and, in particular, strong induction of HO-1 expression. Therefore, the consumption of Nrf2 activators, including glyceollins, should be carefully monitored for patients suffering from certain types of cancer and/or receiving chemotherapy.

Improved extraction of resveratrol and antioxidants from grape peel using heat and enzymatic treatments.

BACKGROUND: Resveratrol, an extensively recognized phytochemical that belongs to the stilbene family, is abundant in grape peel which is discarded as a by-product during grape juice processing. RESULTS: In this study, we established that pre-heating grape peel above 75 °C significantly improved the extractability of resveratrol and its glucoside piceid. In particular, thermal heating of grape peel at 95 °C for 10 min, followed by treatment with a mixture of exo-1,3-ß-glucanase and pectinases at 50 °C for 60 min, dramatically increased the conversion of piceid into resveratrol and the overall extractability of this phytochemical by 50%. Furthermore, thermal pre-treatment promoted a substantial increase in the total phenol, flavonoid, and anthocyanin concentrations in the grape peel extract. Ultimately, resveratrol-enriched grape peel extract significantly augmented the antioxidant response in vitro, possibly by attenuating the accumulation of intracellular reactive oxygen species via the Nrf2 signaling pathway. CONCLUSION: The method developed in this study for preparing grape peel extract introduces a potential low-cost green processing for the industrial fortification of food products with resveratrol and other health-beneficial antioxidants. © 2019 Society of Chemical Industry.

Protective Effects of Dioscorea batatas Flesh and Peel Extracts against Ethanol-Induced Gastric Ulcer in Mice.

Gastric ulcer is a major digestive disorder and provoked by multifactorial etiologies, including excessive alcohol consumption. In this study, we examined the gastroprotective effect of aqueous and ethanolic extracts of Dioscorea batatas Decne (DBD; commonly called Chinese yam) flesh or peel against acidified ethanol-induced acute gastric damage in mice. Our findings demonstrated that oral supplementation of aqueous or ethanolic extracts of DBD flesh or peel before ulcer induction was significantly effective in macroscopically and histologically alleviating ethanol-induced pathological lesions in gastric mucosa, decreasing the plasma levels of inflammatory mediators, such as nitric oxide and interleukin-6, attenuating the gastric expression of cyclooxygenase-2, and increasing the gastric content of prostaglandin E2. In particular, pretreatment with the flesh extract prepared in 60% ethanol prominently decreased the expression of biomarkers of oxidative stress, including the plasma levels of 8-hydroxy-2-guanosine and malondialdehyde, and restored heme oxygenase-1 expression and superoxide dismutase activity in the stomach. Overall, these findings suggest that the oral supplementation with DBD extract, especially flesh ethanol extract, prior to excessive alcohol consumption, may exert a protective effect against ethanol-induced gastric mucosal damage in vivo, presumably through the activation of the antioxidant system and suppression of the inflammatory response.

Effect of Drying Conditions on Nutritional Quality and In Vitro Antioxidant Activity of Traditional Doenjang.

Doenjang, a major traditional Korean condiment, is often dried to reduce volume and thereby shipping cost while increasing shelf life. However, changes of nutritional and sensory properties of doenjang during processing have not been well understood. Therefore, this study aimed to evaluate how drying processes influence the nutritional and chemical properties of doenjang. When two drying methods, hot air drying and freeze drying were compared from the nutritional point of view, air-dried doenjang at 60°C or lower showed similar quality parameters including sensory scores, proximate composition, antioxidant capacity, amino acid composition, amino nitrogen, and acid value to freeze-dried doenjang. In contrast, the sample dried at 80°C and 100°C showed lower quality parameters than the freeze-dried one. Ferric reducing antioxidant potential (FRAP), total phenolics content, amino acid composition, and acid value were shown to reflect the sensory and physical properties of dried doenjang. In particular, the FRAP value of dried doenjang was sensitively responsive to drying temperatures and may be utilized as an early biomarker for quality deterioration of dried doenjang.

Novel (1E,3E,5E)-1,6-bis(Substituted phenyl)hexa-1,3,5-triene Analogs Inhibit Melanogenesis in B16F10 Cells and Zebrafish.

The present study aimed to evaluate the anti-melanogenic activity of 1,6-diphenyl-1,3,5-hexatriene and its derivatives in B16F10 murine melanoma cells and zebrafish embryos. Twenty five (1E,3E,5E)-1,6-bis(substituted phenyl)hexa-1,3,5-triene analogs were synthesized and their non-cytotoxic effects were predictively analyzed using three-dimensional quantitative structure-activity relationship approach. Inhibitory activities of these synthetic compounds against melanin synthesis were determined by evaluating melanin content and melanogenic regulatory enzyme expression in B16F10 cells. The anti-melanogenic activity was verified by observing body pigmentation in zebrafishes treated with these compounds. Compound #2, #4, and #6 effectively decreased melanogenesis induced by α-melanocyte-stimulating hormone. In particular, compound #2 remarkably lowered the mRNA and protein expression levels of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), tyrosinase-related protein 1 (TYRP1), and TYRP2 in B16F10 cells and substantially reduced skin pigmentation in the developed larvae of zebrafish. These findings suggest that compound #2 may be used as an anti-melanogenic agent for cosmetic purpose.

Antioxidant Potential of Selected Korean Edible Plant Extracts.

This study aimed to evaluate the antioxidant activity of various plant extracts. A total of 94 kinds of edible plant extracts obtained from the Korea Plant Extract Bank were screened for cytotoxicity, following which the total phenolic content of 24 shortlisted extracts was determined. Of these, extracts from three plants, namely, Castanea crenata (CC) leaf, Camellia japonica (CJ) fruit, and Viburnum dilatatum (VD) leaf, were examined for antioxidant capabilities by measuring radical scavenging activity, ferric reducing/antioxidant power, and lipid peroxidation inhibitory activity. In addition, cellular antioxidant activities of the three extracts were assessed by a cell-based dichlorofluorescein assay and antioxidant response element (ARE) reporter activity assay. The results demonstrated that all three extracts concentration-dependently scavenged free radicals, inhibited lipid peroxidation, reduced the cellular level of reactive oxygen species, and increased ARE-luciferase activity, indicating antioxidant enzyme-inducing potential. In particular, CJ extract showed significantly greater antioxidative activity and antimigratory effect in a breast cancer cell line compared to CC and VD extracts. Hence, CJ extract deserves further study for its in vivo functionality or biologically active constituents.

Nrf2-Mediated HO-1 Induction and Antineuroinflammatory Activities of Halleridone.

Nuclear factor E2-related factor 2 (Nrf2) is the master regulator of antioxidant enzymes and is known to act on the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Few studies have examined the bioactivity of halleridone. Herein, we investigated whether halleridone, which was isolated from the stems of the plant Cornus walteri, could regulate Nrf2-mediated heme oxygenase (HO)-1 expression and prevent intramicroglial inflammation induced by amyloid beta (Aß)1-42 overexpression. Biochemical and molecular experiments, such as real-time polymerase chain reaction, Western blot analysis, immunocytochemistry, immunofluorescence, and luciferase reporter gene assays, were performed. The results demonstrated that halleridone promoted the upregulation of Nrf2 expression and its translocation to the nucleus, thereby activating antioxidant response element gene transcription and HO-1 expression in murine hippocampal HT22 cells. Additionally, halleridone removed intramicroglial Aß1-42 and suppressed the production of inflammatory mediators such as interleukin (IL)-1ß, IL-6, prostaglandin E2, and nitric oxide (NO) induced by artificially overexpressed Aß1-42 and decreased pNF-κB accumulation in the nucleus and the expression of inducible NO synthase and cyclooxygenase II in BV-2 cells. In conclusion, halleridone activated Nrf2-mediated HO-1 expression and inhibited Aß1-42-overexpressed microglial BV-2 cell activation. These observations suggest that halleridone may have therapeutic potential for targeting neurodegeneration through neuroinflammation.

Protective Effect of Glyceollins in a Mouse Model of Dextran Sulfate Sodium-Induced Colitis.

Glyceollins, which are derived from daidzein in soybean in response to various stimuli or stresses, have been reported to activate antioxidant/detoxifying enzymes in a nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent manner, in addition to exerting anti-inflammatory effects in murine macrophages. As the Nrf2 signaling pathway is known to antagonize nuclear factor (NF)-κB signaling, glyceollins likely have the potential to prevent or treat inflammatory bowel disease. Thus, this study was conducted to examine whether glyceollins could inhibit dextran sulfate sodium (DSS)-induced colitis in a mouse model. Ulcerative colitis (UC) was induced in male BALB/c mice by administering drinking water with 4% DSS for 5 days. Glyceollins (4 or 10 mg/kg of body weight) were orally administered 48 h before and after DSS treatment. We found that glyceollins alleviated histological colon damage and inflammation induced by DSS treatment. More specifically, glyceollins reduced plasma levels of inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, which were otherwise markedly increased by DSS treatment. Markers of tissue damage, including malondialdehyde and 8-hydroxy-2-guanosine, were significantly increased by DSS treatment; however, this effect was mitigated through concomitant treatment with glyceollins. Furthermore, nuclear accumulation of NF-κB p65 and the expression of inducible nitric oxide synthase were upregulated by glyceollins, consistent with the observed modulation of inflammatory markers. In conclusion, glyceollins have therapeutic potential for UC and merit further clinical study.

Suppression of Nrf2 Activity by Chestnut Leaf Extract Increases Chemosensitivity of Breast Cancer Stem Cells to Paclitaxel.

Due to metastatic potential and drug resistance, cancer stem cells (CSCs) have become a critical target for the development of chemotherapeutic agents. Recent studies showed that CSCs highly express NF-E2-related factor 2 (Nrf2)-mediated antioxidant enzymes and thereby retain relatively low levels of reactive oxygen species (ROS). Since anticancer agents usually utilize ROS as an arsenal for killing cancer cells, we hypothesized that inhibition of Nrf2 activity could increase the sensitivity of CSCs to anticancer drugs, and thus enhancing their therapeutic efficacy. We found that MCF-7-derived CSCs with a CD44high/CD24low phenotype formed mammospheres and highly expressed Nrf2 compared to the adherent parental MCF-7 cells. In a separate experiment, we screened 89 different edible plant extracts for inhibitory activity against the Nrf2 signaling pathway by using an antioxidant response element (ARE)-luciferase assay system. Among those extracts, Castanea crenata (chestnut) leaf extract significantly decreased the nuclear translocation of Nrf2 and protein expression of antioxidant enzymes in MCF-7-derived CSCs. The combined treatment of the CSCs with chestnut leaf extract and paclitaxel resulted in more effective cell death than the treatment with paclitaxel alone. These findings suggest that the chestnut leaf extract or its constituents could increase the susceptibility of breast CSCs to an anticancer drug, paclitaxel, through inhibition of the Nrf2 signaling pathway, and could be utilized as an adjuvant for chemotherapy.

Erratum: High-fat Diet Accelerates Intestinal Tumorigenesis Through Disruption Intestinal Cell Membrane Integrity.

[This corrects the article on p. 95 in vol. 21, PMID: 27390738.].

Antioxidant and Neuroprotective Effects of Doenjang Prepared with Rhizopus, Pichia, and Bacillus.

A new type of doenjang was manufactured by mixing soaked soybean, koji (Rhizopus oryzae), cheonggukjang (Bacillus amyloliquefaciens MJ1-4 and B. amyloliquefaciens EMD17), and Pichia farinosa SY80 as a yeast, salt, and water, followed by fermentation with koji that was made by fermenting whole wheat with R. oryzae. The mixed culture doenjang was designed to have a more palatable flavor and stronger biological activities than the conventional product. The extract of mixed culture doenjang showed higher antioxidant activity than the commercial doenjang as evaluated by the ferric reducing antioxidant power assay although it was not significantly different from the commercial product in 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) radical scavenging activities. Further, the mixed culture doenjang reduced intracellular reactive oxygen species levels and protected cells from glutamate-induced cytotoxicity more efficiently in human hippocampal HT22 neuroblastoma cells than the commercial doenjang. In conclusion, a newly-developed mixed culture doenjang had a strong antioxidant activity in vitro and cultured cell model systems, exhibited a potential to prevent oxidative stress-associated disorders although animal and clinical studies are needed to confirm its in vivo efficacy.