Limits...
Investigating the potential of Shikonin as a novel hypertrophic scar treatment.

Fan C, Xie Y, Dong Y, Su Y, Upton Z - J. Biomed. Sci. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

Potential signalling pathways triggered when Kc and HSF are treated with SHI. “” = activation or up-regulation; “” = inhibition or down-regulation
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4537585&req=5

Fig8: Potential signalling pathways triggered when Kc and HSF are treated with SHI. “” = activation or up-regulation; “” = inhibition or down-regulation

Mentions: In light of this significant body of evidence, we examined which signal transduction pathways were involved in mediating the effects of SHI. The data reported here indicates that SHI-induced reduction of cell proliferation in Kc and HSF may be triggered via the ERK1/2, JNK1/2 and p38α/β signalling pathways. In addition, our results show that SHI induces apoptosis by differentially regulating the expression of Bcl-2, Bax, Cytochrome c and caspase 3. Moreover, our data demonstrated that p-ERK is an up-stream regulator mediating the expression of Bcl-2 and caspase 3. It has been reported that reduced Bcl-2 and increased Bax expression leads to the release of Cytochrome c from the mitochondria to the cytoplasm [45, 46]. Cytochrome c then combines with Apoptotic protease activating factor 1(Apaf-1), which further activates caspase 3 to trigger cell apoptosis [47]. These putative mechanisms are schematically summarised in Fig. 8.Fig. 8


Investigating the potential of Shikonin as a novel hypertrophic scar treatment.

Fan C, Xie Y, Dong Y, Su Y, Upton Z - J. Biomed. Sci. (2015)

Potential signalling pathways triggered when Kc and HSF are treated with SHI. “” = activation or up-regulation; “” = inhibition or down-regulation
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4537585&req=5

Fig8: Potential signalling pathways triggered when Kc and HSF are treated with SHI. “” = activation or up-regulation; “” = inhibition or down-regulation
Mentions: In light of this significant body of evidence, we examined which signal transduction pathways were involved in mediating the effects of SHI. The data reported here indicates that SHI-induced reduction of cell proliferation in Kc and HSF may be triggered via the ERK1/2, JNK1/2 and p38α/β signalling pathways. In addition, our results show that SHI induces apoptosis by differentially regulating the expression of Bcl-2, Bax, Cytochrome c and caspase 3. Moreover, our data demonstrated that p-ERK is an up-stream regulator mediating the expression of Bcl-2 and caspase 3. It has been reported that reduced Bcl-2 and increased Bax expression leads to the release of Cytochrome c from the mitochondria to the cytoplasm [45, 46]. Cytochrome c then combines with Apoptotic protease activating factor 1(Apaf-1), which further activates caspase 3 to trigger cell apoptosis [47]. These putative mechanisms are schematically summarised in Fig. 8.Fig. 8

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: 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.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus