Macroalgae-Inspired Brominated Chalcones as Cosmetic Ingredients with the Potential to Target Skin Inflammaging

Area of Science:

• Natural Product Chemistry
• Dermatology
• Pharmacology

Background:

• Skin aging is primarily driven by external factors like UV radiation, leading to oxidative stress and inflammation.
• Halogenated flavonoids from natural sources exhibit anti-inflammatory properties.
• Macroalgae-derived bromophenol BDDE served as inspiration for exploring related chalcones.

Purpose of the Study:

• To investigate the anti-inflammatory potential of synthetic chalcones (1-7) related to BDDE.
• To identify chalcones with low cytotoxicity and potent anti-inflammatory activity.
• To elucidate the mechanism of action for promising anti-inflammatory chalcones.

Main Methods:

• Cytotoxicity assessment in keratinocyte and macrophage cell lines.
• In vitro anti-inflammatory assays using lipopolysaccharide-stimulated murine macrophages.
• Nitric oxide (NO) scavenging assay (SNAP assay).
• Western blot analysis to determine protein levels of inducible nitric oxide synthase (iNOS).
• Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation assay.

Main Results:

• Chalcones 1 and 7 displayed minimal cytotoxicity.
• Chalcones 1, 2, 4, and 5 demonstrated significant anti-inflammatory effects, with Chalcone 1 showing the lowest IC50 value (0.58 μM).
• Anti-inflammatory activity correlated with symmetrical bromine atoms and 3,4-dimethoxy groups.
• Chalcone 2 rapidly inhibited iNOS protein levels, while Chalcone 1 showed gradual inhibition.
• Chalcone 1 significantly activated the Nrf2 pathway, indicating antioxidant potential.

Conclusions:

• Chalcone 1 exhibits potent anti-inflammatory and antioxidant properties, suggesting its utility in skincare.
• The study identified a structure-activity relationship for anti-inflammatory chalcones.
• Chalcone 1 is a promising candidate for developing cosmeceuticals targeting skin aging and inflammation.