Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function

Stratum corneum (SC) pH regulates skin barrier functions and elevated SC pH is an important factor in various inflammatory skin diseases. Acidic topical formulas have emerged as treatments for impaired skin barriers. Sodium proton exchanger 1 (NHE1) is an important factor in SC acidification. We inv...

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Main Authors: Seung-Won Jung, Gi Hyun Park, Eunjung Kim, Kang Min Yoo, Hea Won Kim, Jin Soo Lee, Min Youl Chang, Kyong-Oh Shin, Kyungho Park, Eung Ho Choi
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/7/3910
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author Seung-Won Jung
Gi Hyun Park
Eunjung Kim
Kang Min Yoo
Hea Won Kim
Jin Soo Lee
Min Youl Chang
Kyong-Oh Shin
Kyungho Park
Eung Ho Choi
author_facet Seung-Won Jung
Gi Hyun Park
Eunjung Kim
Kang Min Yoo
Hea Won Kim
Jin Soo Lee
Min Youl Chang
Kyong-Oh Shin
Kyungho Park
Eung Ho Choi
author_sort Seung-Won Jung
collection DOAJ
description Stratum corneum (SC) pH regulates skin barrier functions and elevated SC pH is an important factor in various inflammatory skin diseases. Acidic topical formulas have emerged as treatments for impaired skin barriers. Sodium proton exchanger 1 (NHE1) is an important factor in SC acidification. We investigated whether topical applications containing an NHE1 activator could improve skin barrier functions. We screened plant extracts to identify NHE1 activators in vitro and found <i>Melissa officinalis</i> leaf extract. Rosmarinic acid, a component of <i>Melissa officinalis</i> leaf extract, significantly increased NHE1 mRNA expression levels and NHE1 production. Immunofluorescence staining of NHE1 in 3D-cultured skin revealed greater upregulation of NHE1 expression by NHE1 activator cream, compared to vehicle cream. Epidermal lipid analysis revealed that the ceramide level was significantly higher upon application of the NHE1 activator cream on 3D-cultured skin, compared to application of a vehicle cream. In a clinical study of 50–60-year-old adult females (<i>n</i> = 21), application of the NHE1 activator-containing cream significantly improved skin barrier functions by reducing skin surface pH and transepidermal water loss and increasing skin hydration, compared to patients who applied vehicle cream and those receiving no treatment. Thus, creams containing NHE1 activators, such as rosmarinic acid, could help maintain or recover skin barrier functions.
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spelling doaj.art-1c83ce4305db49f18c89ecc152725b262023-11-30T23:23:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-03-01237391010.3390/ijms23073910Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier FunctionSeung-Won Jung0Gi Hyun Park1Eunjung Kim2Kang Min Yoo3Hea Won Kim4Jin Soo Lee5Min Youl Chang6Kyong-Oh Shin7Kyungho Park8Eung Ho Choi9Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaCMS LAB, Seoul 35324, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaCMS LAB, Seoul 35324, KoreaCMS LAB, Seoul 35324, KoreaCMS LAB, Seoul 35324, KoreaSKINMED Clinical Trials Center, Daejeon 25437, KoreaDepartment of Food Science and Nutrition, Convergence Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, KoreaDepartment of Food Science and Nutrition, Convergence Program of Material Science for Medicine and Pharmaceutics, Hallym University, Chuncheon 24252, KoreaDepartment of Dermatology, Yonsei University Wonju College of Medicine, Wonju 26426, KoreaStratum corneum (SC) pH regulates skin barrier functions and elevated SC pH is an important factor in various inflammatory skin diseases. Acidic topical formulas have emerged as treatments for impaired skin barriers. Sodium proton exchanger 1 (NHE1) is an important factor in SC acidification. We investigated whether topical applications containing an NHE1 activator could improve skin barrier functions. We screened plant extracts to identify NHE1 activators in vitro and found <i>Melissa officinalis</i> leaf extract. Rosmarinic acid, a component of <i>Melissa officinalis</i> leaf extract, significantly increased NHE1 mRNA expression levels and NHE1 production. Immunofluorescence staining of NHE1 in 3D-cultured skin revealed greater upregulation of NHE1 expression by NHE1 activator cream, compared to vehicle cream. Epidermal lipid analysis revealed that the ceramide level was significantly higher upon application of the NHE1 activator cream on 3D-cultured skin, compared to application of a vehicle cream. In a clinical study of 50–60-year-old adult females (<i>n</i> = 21), application of the NHE1 activator-containing cream significantly improved skin barrier functions by reducing skin surface pH and transepidermal water loss and increasing skin hydration, compared to patients who applied vehicle cream and those receiving no treatment. Thus, creams containing NHE1 activators, such as rosmarinic acid, could help maintain or recover skin barrier functions.https://www.mdpi.com/1422-0067/23/7/3910skin barrierskin pHsodium proton exchanger 1<i>Melissa officinalis</i> leaf extractrosmarinic acid
spellingShingle Seung-Won Jung
Gi Hyun Park
Eunjung Kim
Kang Min Yoo
Hea Won Kim
Jin Soo Lee
Min Youl Chang
Kyong-Oh Shin
Kyungho Park
Eung Ho Choi
Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function
International Journal of Molecular Sciences
skin barrier
skin pH
sodium proton exchanger 1
<i>Melissa officinalis</i> leaf extract
rosmarinic acid
title Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function
title_full Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function
title_fullStr Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function
title_full_unstemmed Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function
title_short Rosmarinic Acid, as an NHE1 Activator, Decreases Skin Surface pH and Improves the Skin Barrier Function
title_sort rosmarinic acid as an nhe1 activator decreases skin surface ph and improves the skin barrier function
topic skin barrier
skin pH
sodium proton exchanger 1
<i>Melissa officinalis</i> leaf extract
rosmarinic acid
url https://www.mdpi.com/1422-0067/23/7/3910
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