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Article

Neuroprotective and Anti-Inflammatory Effects of Kuwanon C from Cudrania tricuspidata Are Mediated by Heme Oxygenase-1 in HT22 Hippocampal Cells, RAW264.7 Macrophage, and BV2 Microglia

1
College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, Korea
2
Institute of Pharmaceutical Research and Development, College of Pharmacy, Wonkwang University, Iksan 54538, Korea
3
Hanbang Cardio-Renal Syndrome Research Center, Wonkwang University, Iksan 54538, Korea
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(14), 4839; https://doi.org/10.3390/ijms21144839
Received: 19 June 2020 / Revised: 3 July 2020 / Accepted: 6 July 2020 / Published: 8 July 2020
Heme oxygenase (HO)-1 is a detoxifying phase II enzyme that plays a role in both inflammatory and oxidative stress responses. Curdrania tricuspidata is widespread throughout East Asia and is used as a therapeutic agent in traditional medicine. We investigated whether treatment with sixteen flavonoid or xanthone compounds from C. tricuspidata could induce HO-1 expression in HT22 hippocampal cells, RAW264.7 macrophage, and BV2 microglia. In these compounds, kuwanon C showed the most remarkable HO-1 expression effects. In addition, treatment with kuwanon C reduced cytoplasmic nuclear erythroid 2-related factor (Nrf2) expression and increased Nrf2 expression in the nucleus. Significant inhibition of glutamate-induced oxidative injury and induction of reactive oxygen species (ROS) occurred when HT22 hippocampal cells were pretreated with kuwanon C. The levels of inflammatory mediator and cytokine, which increased following lipopolysaccharide (LPS) stimulation, were suppressed in RAW264.7 macrophage and BV2 microglia after kuwanon C pretreatment. Kuwanon C also attenuated p65 DNA binding and translocation into the nucleus in LPS-induced RAW264.7 and BV2 cells. The anti-inflammatory, anti-neuroinflammatory, and neuroprotective effects of kuwanon C were reversed when co-treatment with HO-1 inhibitor of tin protoporphyrin-IX (SnPP). These results suggest that the neuroprotective and anti-inflammatory effects of kuwanon C are regulated by HO-1 expression. View Full-Text
Keywords: heme oxygenase-1 regulation; Curdrania tricuspidata; kuwanon C; HT22 hippocampal cells; BV2 microglia; RAW264.7 macrophage heme oxygenase-1 regulation; Curdrania tricuspidata; kuwanon C; HT22 hippocampal cells; BV2 microglia; RAW264.7 macrophage
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MDPI and ACS Style

Ko, W.; Yoon, C.-S.; Kim, K.-W.; Lee, H.; Kim, N.; Woo, E.-R.; Kim, Y.-C.; Kang, D.G.; Lee, H.S.; Oh, H.; Lee, D.-S. Neuroprotective and Anti-Inflammatory Effects of Kuwanon C from Cudrania tricuspidata Are Mediated by Heme Oxygenase-1 in HT22 Hippocampal Cells, RAW264.7 Macrophage, and BV2 Microglia. Int. J. Mol. Sci. 2020, 21, 4839. https://doi.org/10.3390/ijms21144839

AMA Style

Ko W, Yoon C-S, Kim K-W, Lee H, Kim N, Woo E-R, Kim Y-C, Kang DG, Lee HS, Oh H, Lee D-S. Neuroprotective and Anti-Inflammatory Effects of Kuwanon C from Cudrania tricuspidata Are Mediated by Heme Oxygenase-1 in HT22 Hippocampal Cells, RAW264.7 Macrophage, and BV2 Microglia. International Journal of Molecular Sciences. 2020; 21(14):4839. https://doi.org/10.3390/ijms21144839

Chicago/Turabian Style

Ko, Wonmin, Chi-Su Yoon, Kwan-Woo Kim, Hwan Lee, Nayeon Kim, Eun-Rhan Woo, Youn-Chul Kim, Dae G. Kang, Ho S. Lee, Hyuncheol Oh, and Dong-Sung Lee. 2020. "Neuroprotective and Anti-Inflammatory Effects of Kuwanon C from Cudrania tricuspidata Are Mediated by Heme Oxygenase-1 in HT22 Hippocampal Cells, RAW264.7 Macrophage, and BV2 Microglia" International Journal of Molecular Sciences 21, no. 14: 4839. https://doi.org/10.3390/ijms21144839

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