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. 2020 Dec 18;12(12):1234.
doi: 10.3390/pharmaceutics12121234.

A Mixture of Tocopherol Acetate and L-Menthol Synergistically Promotes Hair Growth in C57BL/6 Mice

Seunghyun Ahn  1 , Jung Yeon Lee  1 , Sang Mi Choi  1 , Yujeong Shin  1 , Seyeon Park  1
Affiliations

A Mixture of Tocopherol Acetate and L-Menthol Synergistically Promotes Hair Growth in C57BL/6 Mice

Seunghyun Ahn et al. Pharmaceutics. .

Abstract

Oral finasteride and topical minoxidil are single components approved by the US FDA for treating hair loss. Some other compounds originating from natural products are also traditionally used for promoting hair growth. In this study, observations of treated keratinocyte cells were used to demonstrate that tocopherol acetate, L-menthol, and stevioside exert an effect on cell regeneration. Furthermore, these were topically applied to the shaved skin of C57BL/6 mice to observe their effects on hair growth. A mixture of tocopherol acetate, L-menthol, and stevioside showed the highest potential for promoting hair growth in vivo. In in vivo experiments, the mixture of tocopherol acetate, L-menthol, and stevioside was more effective than tocopherol acetate or L-menthol alone in promoting hair growth. The transcriptome analysis of skin from the dorsal side of a mouse treated with tocopherol acetate or L-menthol versus vehicle revealed key changes in keratin, keratin-associated protein, forkhead box, sonic hedgehog, fibroblast growth factor 10, desmoglein 4, deoxyribonuclease 1-like 2, and cadherin 3, known to play roles in promoting hair growth.

Keywords: functional gene clustering; hair cycle-related gene; skin development; synergistic effect; transcriptome analysis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
I Effects of (A) tocopherol acetate, (B) stevioside, (C) L-menthol, and (D) minoxidil on keratinocyte proliferation. Cells were treated with each compound at indicated concentrations for 24 and 48 h. Results are presented as average and standard deviation. Statistical analyses were performed in comparison with the vehicle-treated control group (* p < 0.05; ** p < 0.01; n = 6). II Effects of (A) tocopherol acetate, (B) stevioside, (C) L-menthol, and (D) minoxidil on human hair follicle dermal papilla (HDP) cell proliferation. Cells were treated with each compound at indicated concentrations for 24 and 48 h. Results are presented as average and standard deviation. Statistical analyses were performed in comparison with the vehicle-treated control group (* p < 0.05; ** p < 0.01; n = 3).
Figure 2
Figure 2
Effects of topical application of tocopherol acetate, stevioside, L-menthol, and their mixture on hair growth induction in C57BL/6 mice. Mice were divided into 6 groups: CTR (control), minoxidil, L-menthol, tocopherol acetate, stevioside, and L-menthol + tocopherol acetate + stevioside. Time scale of hair regrowth in C57BL/6 mice during 8 weeks post-shaving. The skin on the back of each mouse was photographed every week.
Figure 3
Figure 3
Quantitative comparison of hair growth. The hair growth area was scanned and measured with Image J. The value is represented as the percentage of the hair growth area relative to the shaved area. The average value is shown, with error bar indicating standard deviation. The calculations excluded the highest and lowest values in each group. Statistical analyses were performed in comparison with the vehicle-treated control group (* p < 0.05; ** p < 0.01; n = 3).
Figure 4
Figure 4
Heat map of gene expression levels for tocopherol acetate vs. CTR, L-menthol vs. CTR, L-menthol + tocopherol acetate + stevioside vs. CTR, minoxidil vs. CTR, and stevioside vs. CTR. Significant genes were defined as those with a 3-fold change, normalized data of 5.00, and p-value < 0.05. Hierarchical clustering was performed in the functional category of hair growth. CTR = control
Figure 5
Figure 5
Gene category chart of (A) tocopherol acetate vs. CTR, (B) L-menthol vs. CTR, (C), L-menthol + tocopherol acetate + stevioside vs. CTR, (D) minoxidil vs. CTR and (E) stevioside vs. CTR. CTR = control
Figure 6
Figure 6
Functional annotation enrichment for tocopherol acetate (A) and L-menthol (B) treatment groups. DAVID bioinformatics resources 6.8 analysis tool was used.
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