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.

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.

Korean red ginseng (Panax ginseng C.A. Meyer) contains various pharmacologically active constituents including ginsenosides. Recently we found that red ginseng extract has a strong antioxidant activity and that pectinase‐mediated hydrolysis augments its radical‐scavenging activity. In addition, the content of compound‐K, a bioavailable and bioactive ginsenoside, was significantly increased in the hydrolyzed red ginseng extract compared to the non‐hydrolyzed extract. We further investigated neuroprotective and cognitive‐enhancing effects of the hydrolyzed red ginseng extract in vitro and in vivo. To induce oxidative stress‐induced neurotoxicity, mouse hippocampal HT22 cells and C57BL/6 mice were exposed to an excess glutamate and D‐galactose, respectively. For behavioral assessments, the passive avoidance, Y‐maze, and Morris water maze tasks were performed following treatment with the extracts or compound‐K. Our results from the in vitro and in vivo tests demonstrate that (1) red ginseng extract (containing compound‐K) protects neuronal cells from oxidative damage through the induction of Nrf2 and antioxidant enzymes, (2) the learning and memory impairments induced by oxidative stress were alleviated by treatment with the hydrolyzed red ginseng extract, (3) the hippocampi (particularly cell counts and nuclear arrangement) of the stressed mice was histologically pathologic, which was rarely observable from the hippocampi of the extract‐treated mice. Our findings suggest that red ginseng extract hydrolyzed by pectinase may effectively alleviate oxidative stress‐mediated memory deficits possibly through Nrf2‐related detoxification.Support or Funding InformationThis work was supported by the Food Functionality Evaluation program funded by the Ministry of Agriculture, Food and Rural Affairs through Korea Food Research Institute.

Salicornia herbacea L., also called as glasswort, is a halophyte growing in salt marshes and has been used as a seasoned vegetable and a traditional medicine for various disorders. It is a nutrient‐rich herb containing plenty of bioactive compounds such as selenium, flavonoids. In this study, we in vitro examined if ethanol extract from glasswort is neuroprotective under oxidative stress‐induced environment. Hippocampal HT22 cells were treated with 5 mM glutamate in the presence of ethanol extract from glasswort or its subfractions in five different solvents (hexane, methylene chloride, ethyl acetate, butanol, and water). Ethanol (EtOH) extract and methylene chloride‐soluble subfraction (MC fraction) of the herb were effective in protecting HT22 cells from glutamate‐induced toxicity. In addition, EtOH extract and MC fraction induced intracellular antioxidant enzyme NQO1's activity and inhibited ROS production. The levels of Nrf2 and its downstream antioxidant enzymes were significantly elevated by both EtOH extract and MC fraction. We further investigated whether MC fraction is protective against galactose‐induced cognitive decline in animal model. C57BL/6J mice were fed MC fraction, and intraperitoneally injected with D‐galactose on a daily‐basis to generate oxidative stress and cause learning and memory impairments. After 6 weeks, behavioral and biochemical tests were conducted. The group fed MC fraction decreased escape latency time, reduced DNA damage and lipid peroxidation, and enhanced NQO1 enzyme activity in tissues, compared to D‐galactose‐treated control group. Overall, these findings suggest that MC fraction of glasswort extract could be a promising agent for AD prevention.Support or Funding InformationThis work was supported by the Food Functionality Evaluation program funded by the Ministry of Agriculture, Food and Rural Affairs through Korea Food Research Institute, and by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (Project No. 2013R1A1A2013362).