Investigating the potential of Shikonin as a novel hypertrophic scar treatment.
BACKGROUND
Hypertrophic scarring is a highly prevalent condition clinically and results from a decreased number of apoptotic fibroblasts and over-abundant production of collagen during scar formation following wound healing. Our previous studies indicated that Shikonin, an active component extracted from Radix Arnebiae, induces apoptosis and reduces collagen production in hypertrophic scar-derived fibroblasts. In the study reported here, we further evaluate the potential use of Shikonin as a novel scar remediation therapy by examining the effects of Shikonin on both keratinocytes and fibroblasts using Transwell® co-culture techniques. The underlying mechanisms were also revealed. In addition, effects of Shikonin on the expression of cytokines in Transwell co-culture "conditioned" medium were investigated.


RESULTS
Our results indicate that Shikonin preferentially inhibits cell proliferation and induces apoptosis in fibroblasts without affecting keratinocyte function. In addition, we found that the proliferation-inhibiting and apoptosis-inducing abilities of SHI might be triggered via MAPK and Bcl-2/Caspase 3 signalling pathways. Furthermore, SHI has been found to attenuate the expression of TGF-β1 in Transwell co-cultured "conditioned" medium.


CONCLUSIONS
The data generated from this study provides further evidence that supports the potential use of Shikonin as a novel scar remediation therapy.
Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, 4059, Australia. c3.fan@connect.qut.edu.au.
Chen
C
Fan
Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, 4059, Australia. y2.xie@qut.edu.au.|Tissue Organ Bank & Tissue Engineering Centre, General Hospital of Ningxia Medical University, Yinchuan, China. y2.xie@qut.edu.au.
Yan
Y
Xie
Cancer Research Program, Translational Research Institute, Queensland University of Technology, Brisbane, Australia. y.dong@qut.edu.au.
Ying
Y
Dong
Changhai Hospital of Traditional Chinese Medicine, Second Military Medical University, Shanghai, China. suyh2001@126.com.
Yonghua
Y
Su
Tissue Repair and Regeneration Program, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, 4059, Australia. z.upton@qut.edu.au.
Zee
Z
Upton
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D017439:Cicatrix, Hypertrophic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018920:Coculture Techniques; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D009285:Naphthoquinones / Q000494:pharmacology*
D009285:Naphthoquinones; C016101:shikonin; D003094:Collagen