Jisun Oh

Neuroprotective and Cognition-Enhancing Effects of Compound K Isolated from Red Ginseng

The present study was aimed at elucidating the effect of compound K derived from red ginseng on memory function in mouse model and glutamate-induced cytotoxicity in mouse hippocampal HT22 cells. Compound K induced antioxidant enzymes in nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated manner, and effectively attenuated cytotoxicity and mitochondrial damage induced by glutamate in HT22 cells. However, the cytoprotective effect by compound K was abolished by heme oxygenase-1 inhibitor, tin protophorphyrin IX, suggesting that neuroprotective effect of compound K was caused by its Nrf2-mediated induction of antioxidant enzymes. Further, memory deficit induced by scopolamine was restored by compound K, which did not inhibit acetylcholine esterase, in C57BL/6 mice but not in Nrf2 knockout mice as assessed by passive avoidance test, Y-maze and water maze tests, suggesting that scopolamine-induced memory impairment was overcome by the induction of Nrf2-mediated antioxidant enzymes by the compound K. Overall, our data indicate that compound K could be useful in prevention and treatment of reactive oxygen species-induced neurological disorders such as Alzheimers disease.

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.

In vitro and in vivo anti-inflammatory activities of mixed fruit and vegetable juice

In this study, we attempted to develop fruit-based functional juice with anti-inflammatory activity for consumers living under heavy air pollution. At first, four different formulations for functional juice prepared by combining 10 kinds of fruits and other ingredients in various ratios were tested for NAD(P)H: quinoneoxidoreductase 1 (NQO1)-inducing activity in mouse hepatoma Hepa1c1c7 cells. The formulation showing the highest NQO1-inducing activity [named detoxification juice (DJ)] was investigated for its anti-inflammatory activity in a co-culture system of human lung carcinoma A549 cell line and a differentiated human monocytic cell line THP-1. DJ significantly reduced the LPS-induced production of proinflammatory cytokines, such as interleukin-6 (IL-6), IL-1β, and tumor necrosis factor α (TNF-α). Furthermore, DJ administration suppressed the benzo[a]pyreneinduced elevation of plasma cytokine levels of C57BL/6 mice. However, the protective effect of DJ against inflammation in lung and trachea caused by air pollution needs to be assessed through clinical studies.