# Influence of sodium Bituminosulfonate and Doxycycline on signal molecules relevant for rosacea symptoms

## TL;DR

This study explores how sodium bituminosulfonate and doxycycline reduce inflammation and blood vessel growth in rosacea by affecting specific signaling molecules.

## Contribution

The study reveals distinct and overlapping molecular mechanisms of SBDS and doxycycline in modulating inflammatory and angiogenic pathways in rosacea.

## Key findings

- SBDS inhibits COX-1 and COX-2 activity, reducing PGE2 and TXB2 release in inflamed monocytes.
- SBDS and doxycycline both inhibit VEGF release in mast cells under inflammatory conditions.
- Neither drug affects LL37 release, suggesting a selective anti-inflammatory effect.

## Abstract

Rosacea is treated among others by doxycycline and sodium bituminosulfonate dry substance (SBDS). We addressed the molecular mechanism(s) underlying the therapeutic benefit of SBDS and doxycycline. Therefore, we investigated whether SBDS or doxycycline regulates the expression of signal molecules relevant for inflammatory and angiogenic effects. Cyclooxygenase 1 (COX1) and COX2 activity assays were assessed in primary human monocytes. The release of nitric oxide (NO) and their synthesizing enzyme inducible nitric oxide synthase (iNOS), VEGF and LL37 release were determined in lung epithelial cells A549, mast cells HMC 1.2 or in normal human epidermal keratinocytes (NHEKs), respectively. The IC50 values of SBDS for the inhibition of recombinant human COX-1 and COX-2 were 1.9 and 8.3 µg/ml, respectively. In an inflammatory state (COX-2 expression) 100 µg/ml SBDS reduced PGE2 and TXB2 release in primary human monocytes. 25 µg/ml SBDS inhibited the mRNA and protein expression of iNOS. Moreover, 50 µg/ml SBDS and 30 µg/ml doxycycline inhibited the release of VEGF in an inflammatory state in HMC 1.2 cells. Both drugs did not affect LL37 release. Doxycycline did not affect intracellular NO levels and iNOS expression. SBDS and doxycycline mediate anti-inflammatory and anti-angiogenic effects through similar but also different signaling molecules.

The online version contains supplementary material available at 10.1038/s41598-025-02796-0.