Application of “macromolecular crowding” in vitro to investigate the naphthoquinones shikonin, naphthazarin and related analogues for the treatment of dermal scars

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Application of “macromolecular crowding” in vitro to investigate the naphthoquinones shikonin, naphthazarin and related analogues for the treatment of dermal scars
Title:
Application of “macromolecular crowding” in vitro to investigate the naphthoquinones shikonin, naphthazarin and related analogues for the treatment of dermal scars
Journal Title:
Chemico-Biological Interactions
Publication Date:
10 July 2019
Citation:
Fan, C., Lim, L. K. P., Loh, S. Q., Ying Lim, K. Y., Upton, Z., & Leavesley, D. (2019). Application of “macromolecular crowding” in vitro to investigate the naphthoquinones shikonin, naphthazarin and related analogues for the treatment of dermal scars. Chemico-Biological Interactions, 310, 108747. doi:10.1016/j.cbi.2019.108747
Abstract:
Pathological scarring is an intractable problem for both patients and clinicians. A major obstacle for the development of scar remediation therapies is the paucity of suitable in vivo and in vitro models. The "Scar-in-a-jar" model was previously established by our colleagues based on the principle of "Macromolecular crowding". This has been demonstrated to be an extracellular matrix-rich in vitro model offering a novel tool for studies related to the extracellular matrix. In the study reported herein, we have optimised this approach to model human dermal fibroblasts derived from hypertrophic tissues. This optimised in vitro model has been found to hold similar properties, such as increased collagen I, interleukins and transforming growth factor beta-1 expression, compared to that observed in hypertrophic scar tissue in vivo. In addition, Shikonin has been previously demonstrated to hold potential as a novel hypertrophic scar treatment due to its apoptosis-inducing property on hypertrophic scar fibroblasts. Other Shikonin analogues have also been reported to hold apoptosis-inducing properties in various cancer cell lines, however, the effects of these analogues on hypertrophic scar-related cells are unknown. We therefore evaluated the effects of Shikonin and its analogues on hypertrophic scar-derived human fibroblasts using the optimised "Macromolecular crowding" model. Our data indicates that Shikonin and Naphthazarin are the most effective molecules compared to related naphthoquinones. The data generated from the study offers a novel in vitro collagen-rich model of hypertrophic scar tissue. It also provides further evidences supporting the use of Shikonin and Naphthazarin as potential treatments for hypertrophic scars.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This research / project is supported by the HBMS - IAF-PP
Grant Reference no. : H17/01/a0/009
Description:
ISSN:
0009-2797
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