Inhibition of Stromelysin-1 by Caffeic Acid Derivatives from a Propolis Sample from Algeria

Abstract

Stromelysin-1 (matrix metalloproteinase-3: MMP-3) occupies a central position in collagenolytic and elastolytic cascades, leading to cutaneous intrinsic and extrinsic aging. We screened extracts of a propolis sample from Algeria with the aim to isolate compounds able to selectively inhibit this enzyme. A butanolic extract (B₃) of the investigated propolis sample was found to potently inhibit MMP-3 activity (IC₅₀ = 0.15 ± 0.03 µg/mL), with no or only weak activity on other MMPs. This fraction also inhibited plasmin amidolytic activity (IC₅₀ = 0.05 µg/mL) and impeded plasmin-mediated proMMP-3 activation. B₃ was fractionated by HPLC, and one compound, characterized by NMR and mass spectroscopy and not previously identified in propolis, i.e., (+)-chicoric acid, displayed potent in vitro MMP-3 inhibitory activity (IC₅₀ = 6.3 × 10⁻⁷ M). In addition, both caffeic acid and (+)-chicoric acid methyl ester present in fraction B₃ significantly inhibited UVA-mediated MMP-3 upregulation by fibroblasts.

Key words

propolis - matrix metalloproteinase (MMP) - MMP‐3 inhibitors - plasmin - caffeic acid - chicoric acid

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