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Article

Opposing Effect of Naringenin and Quercetin on the Junctional Compartment of MDCK II Cells to Modulate the Tight Junction

1
Graduate School of Pharmaceutical Sciences, Nagoya University, Furocho, Chikusa, Nagoya, Aichi 464-8601, Japan
2
Department of Biological Sciences, Faculty of Science, Nagoya University, Furocho, Chikusa, Nagoya, Aichi 464-8602, Japan
3
BeCerllBar, LLC., Business Incubation Building, Nagoya University, Furocho, Chikusa-ku, Nagoya, Aichi 464-8601, Japan
4
Cosmetics Research Department, Nicca Chemical Co. Ltd., Fukui 910-8670, Japan
*
Author to whom correspondence should be addressed.
Present Address: Research Center, Koken Co. Ltd., 2-13-10, Ukima, Kita-ku, Tokyo 115-0051, Japan.
Nutrients 2020, 12(11), 3285; https://doi.org/10.3390/nu12113285
Received: 15 September 2020 / Revised: 16 October 2020 / Accepted: 23 October 2020 / Published: 27 October 2020
Maintaining tight junction (TJ) integrity is important for epithelial cell barriers. Previously, the enhancement of TJ integrity, induced by citrus-derived flavonoids, naringin (NRG) and hesperidin (HSD), was demonstrated, but the effects of their aglycones naringenin (NAR) and hesperetin (HST), and the mechanisms, have not been systematically investigated. Here we compared three series of flavonoids related to NAR, HST, quercetin (QUE) and their glycosides with the Madin–Darby canine kidney (MDCK) II cell monolayers. The effect of flavonoids on the protein expression level of claudin (CLD)-2 and its subcellular localization were investigated. NAR, NRG, and HSD increased the CLD-2 localization at the TJ compartment, and its protein expression level. QUE and HST showed TJ-mitigating activity. Narirutin (NRT), neohesperidin (NHD) and rutin (RUT) did not affect the TJ. In addition, NAR and QUE induced an increase or decrease of the transepithelial electrical resistance (TEER) values of the MDCK II monolayers. Two known signaling pathways, phosphatidyl-inositol-3 kinase (PI3K) and 5′-AMP-activated protein kinase (AMPK), were further compared with NAR. Two-dimensional polyacrylamide electrophoresis (2D PAGE) analysis of whole-cell proteins treated with NAR, AICA-riboside (AMPK activator) and LY294002 (PI3K inhibitor) showed in both a distinct pattern. This suggests the target of NAR’s CLD-2 or zonula occludens-1 (ZO-1) modulation was unique. View Full-Text
Keywords: dynamic equilibrium of tight junction; flavonoids; epithelial barrier enhancer; 5′ adenosine monophosphate (AMP)-activated protein kinase; phosphatidylinositol-3-phosphate kinase; tight junction integrity dynamic equilibrium of tight junction; flavonoids; epithelial barrier enhancer; 5′ adenosine monophosphate (AMP)-activated protein kinase; phosphatidylinositol-3-phosphate kinase; tight junction integrity
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MDPI and ACS Style

Nakashima, M.; Hisada, M.; Goda, N.; Tenno, T.; Kotake, A.; Inotsume, Y.; Kameoka, I.; Hiroaki, H. Opposing Effect of Naringenin and Quercetin on the Junctional Compartment of MDCK II Cells to Modulate the Tight Junction. Nutrients 2020, 12, 3285. https://doi.org/10.3390/nu12113285

AMA Style

Nakashima M, Hisada M, Goda N, Tenno T, Kotake A, Inotsume Y, Kameoka I, Hiroaki H. Opposing Effect of Naringenin and Quercetin on the Junctional Compartment of MDCK II Cells to Modulate the Tight Junction. Nutrients. 2020; 12(11):3285. https://doi.org/10.3390/nu12113285

Chicago/Turabian Style

Nakashima, Mio, Misaki Hisada, Natsuko Goda, Takeshi Tenno, Ayaka Kotake, Yuko Inotsume, Ikuo Kameoka, and Hidekazu Hiroaki. 2020. "Opposing Effect of Naringenin and Quercetin on the Junctional Compartment of MDCK II Cells to Modulate the Tight Junction" Nutrients 12, no. 11: 3285. https://doi.org/10.3390/nu12113285

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