Mucopolysaccharide polysulfate increases local skin blood volume through nitric oxide production
Tam Kurachi1, Hironobu Ishimaru1, Ryo Tadakuma1
1Drug Development Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd., Kyoto, Japan.
Background:
Mucopolysaccharide polysulfate (MPS) is widely used as an active ingredient in topical preparations for the treatment of asteatosis and blood flow disorders. Although topical MPS products can increase cutaneous blood flow (CBF), the underlying mechanism remains unclear.
Objective:
In this study, we aimed to elucidate how MPS increases CBF. We investigated the association of nitric oxide (NO), a powerful mediator associated with increased local blood volume, with the blood flow-accelerating action of MPS in mice. In addition, we verified the effects of MPS on NO production in different skin cell types, such as keratinocytes (KCs), endothelial cells (ECs), and dermal fibroblasts (DFs).
Methods:
We used raster-scanning optoacoustic imaging mesoscopy to observe in vivo changes in the skin blood volume. NO production was determined in each cell using an NO indicator. An enzyme-linked immunoassay was used to measure the phosphorylated nitric oxide synthase (NOS) levels in ECs, DFs, and KCs in the presence or absence of MPS.
Results:
Topical application of MPS increased the skin blood volume in mice, and this increase was abolished through the addition of NOS inhibitors. MPS promoted the dose-dependent production of NO in various cells, which caused alterations in the phosphorylation state of NOS.
Conclusion:
Our findings demonstrate that MPS promotes an increase in skin blood volume and NO production in various skin cell types. These results suggest that MPS can potentially accelerate CBF through the NO biosynthesis pathway in different skin cell types.
Insights
Mucopolysaccharide polysulfate (MPS) increases skin blood flow by promoting nitric oxide (NO) production in skin cells. This study clarifies the mechanism behind MPS
Area of Science:
- Dermatology and Vascular Biology
- Pharmacology of Topical Agents
Background:
- Mucopolysaccharide polysulfate (MPS) is a common topical treatment for skin conditions like asteatosis.
- While MPS is known to increase cutaneous blood flow (CBF), the exact mechanism is not well understood.
- Investigating the role of nitric oxide (NO) is crucial for understanding MPS's effects on CBF.
Purpose of the Study:
- To elucidate the mechanism by which MPS increases CBF.
- To investigate the association between nitric oxide (NO) and MPS-induced blood flow acceleration.
- To examine the effect of MPS on NO production in key skin cell types: keratinocytes (KCs), endothelial cells (ECs), and dermal fibroblasts (DFs).
Main Methods:
- Utilized raster-scanning optoacoustic imaging mesoscopy for in vivo observation of skin blood volume changes.
- Quantified NO production in individual cells using a specific NO indicator.
- Employed enzyme-linked immunoassay to measure phosphorylated nitric oxide synthase (NOS) levels in ECs, DFs, and KCs.
Main Results:
- Topical MPS application significantly increased skin blood volume in mice.
- The observed increase in blood volume was negated by the administration of NOS inhibitors.
- MPS demonstrated dose-dependent promotion of NO production across various skin cell types, altering NOS phosphorylation.
Conclusions:
- MPS enhances skin blood volume and stimulates NO production in multiple skin cell types.
- The findings suggest that MPS accelerates CBF via the NO biosynthesis pathway.
- This research provides mechanistic insight into the therapeutic effects of MPS on skin circulation.
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