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In vitro studies of antifibrotic and cytoprotective effects elicited by proto-berberine alkaloids in human dermal fibroblasts

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Abstract

Background

The pathogenic mechanisms of skin fibrosis are still not completely understood, unlike the profibrotic role played by inflammatory cytokines and transforming growth factor-β1 (TGF-β1). Few antifibrotic drugs are available. Nevertheless, folk medicine suggests numerous treatments of fibrotic conditions. Based on information from folk medicine and literature, the hypothesis was made that proto-berberine alkaloids could act as antifibrotic and cytoprotective agents.

Methods

The effects of berberine, dihydroberberine, canadine, stylopine, and coptisine were investigated on an in vitro model of fibrosis purposely set up. The study is based on the use of human dermal fibroblasts (HDF). The ability of the proto-berberine alkaloids investigated to modulate mitochondrial dehydrogenase activity, cell proliferation, collagen production, and inflammatory cytokine (IL-1β and IL-6) production was tested on HDF cells grown under standard growth conditions, in the presence of 100 μM H2O2, simulating oxidative stress conditions, and in the presence of 34 ng/ml TGF-β1, simulating fibrotic conditions. Antiradical activity was assayed as well, as it could contribute to cytoprotection.

Results

Each alkaloid tested showed peculiar effects on HDF. In particular, all of the alkaloids tested, with the exception of coptisine, inhibited TGF-β1-induced collagen production.

Conclusions

Due to its irritant effects and the lack of desired properties, coptisine has low exploitation potentialities. The other proto-berberine alkaloids investigated resulted all endowed with activities for which they can be exploited as antifibrotic and cytoprotective agents. Stylopine globally proved to be the most promising compound, being endowed with revitalizing, anti-inflammatory, antifibrotic and wound-healing promoting activities, and showing no toxic effects.

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Authors and Affiliations

  1. Alidans S.r.l., San Giuliano Terme, Pisa, Italy

    Daniele Pietra & Alice Borghini

  2. Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), Firenze, Italy

    Anna Maria Bianucci

Authors
  1. Daniele Pietra
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  2. Alice Borghini
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  3. Anna Maria Bianucci
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Correspondence to Daniele Pietra.

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Pietra, D., Borghini, A. & Bianucci, A.M. In vitro studies of antifibrotic and cytoprotective effects elicited by proto-berberine alkaloids in human dermal fibroblasts. Pharmacol. Rep 67, 1081–1089 (2015). https://doi.org/10.1016/j.pharep.2015.04.001

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  • DOI: https://doi.org/10.1016/j.pharep.2015.04.001

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