Topically Applied N,N-Dimethylglycine Sodium Salt Enhances Human Skin Blood Flow by Inducing Endothelial Nitric Oxide Release

Béke, Gabriella and Lendvai, Alexandra and Hollósi, Erika and Braun, Nicole and Theek, Carmen and Kállai, Judit and Lányi, Árpád and Becker, Maike and Völker, Jörn Michael and Schulze zur Wiesche, Erik and Bácsi, Attila and Bíró, Tamás and Mihály, Johanna (2024) Topically Applied N,N-Dimethylglycine Sodium Salt Enhances Human Skin Blood Flow by Inducing Endothelial Nitric Oxide Release. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 24. No.-11264. ISSN 0022-202X

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Abstract

We have recently showed that the sodium salt of N,N-Dimethylglycine (DMG-Na) promoted the proliferation of human epidermal keratinocytes and upregulated the synthesis of certain growth factors, and that DMG-Na also exerted robust anti-inflammatory and antioxidant effects in various in vitro dermatitis models. In the current study, we assessed the effects of DMG-Na on human skin microcirculation and endothelium functions. In our in vitro studies, we found that DMG-Na induced a marked and statistically significant (when compared to control) Ca2+ influx into primary cultures of human dermal microvascular endothelial cells (HDMECs) in a dose-dependent manner, increased the expression of endothelial nitric oxide synthase and induced nitric oxide (NO) production. In addition, in a monocentric, single-blinded, randomized, placebo-controlled human in vivo proof-of-concept study, topically applied 1% DMG-Na gel statistically significantly (when compared to placebo and/or untreated control) augmented skin blood flow and skin blood flow velocity. These data provide the first human evidence that topical DMG-Na robustly increases the intensity of dermal microcirculation by penetrating into deeper cutaneous layers, most probably due to its actions on HDMECs where it induces endothelium-derived, NO-dependent vasodilation. Further clinical studies are therefore warranted to explore the enormous application potential of DMG-Na in multiple human skin pathologies.

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