An Exploratory In Vivo Study on the Effect of Annurca Apple Extract on Hair Growth in Mice
, Seoyoon Ham 1,†, Sang Gyu Lee 1, Inhee Jung 3, Jangmi Suk 3, Jinhee Yoo 4, Su-Young Choi 4 and Ju Hee Lee 1,2,*
Neusa Yuriko Sakai Valente
Round 1
Reviewer 1 Report
General comment:
The authors have proved that AAE can induce hair through orally administration in the hair shaving study. However, the mouse skin is composing many types of cells. Authors should be able to prove that the administration of AAE will change the expression of different hair growth markers in the hair organ such as dermal papilla or the stem cell in the bulge by qRT-PCR or ELISA. A more detail molecular pathway can be proposed such as the upregulation of the wnt pathway or downregulation of BMP pathway. The compounds that have the hair growth effect in AAE should be identified.
Detail comments:
2.2 Effect of AAE on gene expressions of growth factors in the C57BL/6 mice skin tissue
1. The skin consists of many cell types. The upregulation of VEGF and FGF-7 should be proved in the hair organ. The authors should be able to detect the change of different hair growth markers in the hair organ such as dermal papilla or the stem cell in the bulge. The authors can culture primary or immortalized dermal papilla to investigate the effect of AAE on hair growth.
2. A more detail molecular pathway can be proposed such as the upregulation of the wnt pathway or downregulation of BMP pathway.
2.4 Expression levels of epidermal cytokeratins after AAE ingestion in the C57BL/6 mice skin
tissue
1. The authors should provide the CK5 and CK10 immunohistochemical staining of mice skin section of hair.
Identified the active compound in AAE
1. The authors should identify the active compound in AAE.
Author Response
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Author Response File: 
Author Response.docx
Reviewer 2 Report
Very interesting and well done research. I have few obvservations:
-line 204: ...increased the local gene expression of 5alfa-reductase..
I think the correct is :....decreased the..........
-There are some different results with low ad high dose of AAE.
Wich dose the authors think is more effective
Author Response
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Author Response File: Author Response.docx
Round 2
Reviewer 1 Report
The authors have tackled most of the round one comment. Some minor problems have to be addressed.
1. CK5 and CK10 on the epidermis seem to be the major proposed hypothesis that explained for the effect of AAE on promoting hair growth. However, the 5α-reductase mentioned in the discussion (Line 221) is expressed in the dermal papilla cell in the dermis layer. Can the authors provide some solid reference of the function of CK5 and CK10 on the epidermis that can protect the hair follicle from external stress in the perspective of androgenetic alopecia?
2. The relative mRNA expression of β-catenin and Dkk1 with the treatment of AAE is not statistically significant. The authors should not put into the manuscript.
Author Response
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Author Response File: Author Response.docx
