• Biomolecules & Therapeutics
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• 제31권5호
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• pp.550-558
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• 2023

Hair loss is a common condition that can have a negative impact on an individual's quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

• Korean Chemical Engineering Research
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• 제44권1호
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• pp.58-64
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• 2006

본 연구에서는 인체 두피조직에서 미세수술법을 이용하여 모낭을 성공적으로 분리하였으며 다양한 조건으로 액침기관배양을 수행하였다. 우태아 혈청첨가시 모낭의 길이 성장이 저해되는 것으로 확인되어 무혈청 배지 조성을 시도하였다. 무혈청 배지로는 모낭 기관배양에 널리 이용되는 Williams'E medium을 기본으로 하는 Philpott medium과 자체 개발한 고농도 아미노산과 비타민(B군) 조성의 DHGM(Dongguk hair growth medium)을 이용하였다. 그리고 IMDM은 DHGM의 비교 대조군으로 이용하였다. 연구 결과 Philpott medium과 IMDM으로 배양한 모낭은 구조상으로는 길이 성장이 각각 9일과 12일 정도에 멈추며, 낮은 알카라인 포스파테이즈 발현, CK19 발현이 거의 없는 것으로 보아 세포사멸에 의한 퇴화(regression)가 빠르게 일어나는 것으로 판단되었다. 반면, DHGM으로 배양한 모낭은 상대적으로 긴 기간 동안 성장기의 구조를 보이며 25일까지 지속적인 길이 증가 및 3배 높은 알카라인 포스파테이즈 발현, 전반적인 CK19 발현을 나타내었다. 따라서 고농도의 아미노산 및 비타민 배지 조성이 생체 외에서 모낭을 장기간 배양하는데 중요한 역할을 하는 것으로 판단된다. 이러한 배양 방법은 장기간 검사를 필요로 하는 모낭에 대한 기초 생물학적 연구뿐만 아니라 새로운 탈모치료제의 효능 평가 분야에 이용될 수 있을 것이다.

• 동의생리병리학회지
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• 제23권1호
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• pp.84-92
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• 2009

This experiment was investigated the effects of fresh and ginger processed Pinelliae Rhizoma extracts on hair growth activity, and its fractions(chloroform, ethyl acetate and water fractions) obtained from fresh Pinelliae Rhizoma on hair growth activity of the normal and spontaneous alopecia areata model of C57BL/6N mice for 16 days. The results were as follows: In fresh Pinelliae Rhizoma extracts treated group, hair growth effect was observed in whole skin area(100%) all the normal mice in whose hair had been clipped on 16th days. In ginger processed Pinelliae Rhizoma extracts treated group, hair growth effect was observed in whole skin area in 25% of normal mice in whose hair had been clipped on 16th days. But in control group, hair growth effect was observed in a part of whole skin area in 25% of normal mice. In fresh Pinelliae Rhizoma extracts treated group, hair follicles of middle stage of anagen phase was observed and it were grown down to subcutaneous tissue of skin in all the mice on 10th day. But in ginger processed Pinelliae Rhizoma extracts treated group and control group, Most of hair follicles of telogen phase was observed in skin. The treatment of extracts of fresh Pinelliae Rhizoma increased the expression of TGF-$\beta$(146%), IGF(107%), and prolactin(115%) in the skin of normal C57BL/6N mice compared to control group(100%). But expression of placenta lactogen(93%) was decreased in the skin of normal C57BL/6N mice compared to control group(100%). In spontaneous alopecia model, The hair growth activity of fresh Pinelliae Rhizoma extracts treated group(100%) was observed to be strong compared with the control group(20%) on 15th day. Hair growth activity on chloroform fractions of fresh Pinelliae Rhizoma extracts was observed in whole skin area in 75% of normal mice on the 9th day. In water and ethyl acetate fractions, hair growth activity was observed in a part of whole skin in 75% and 25% of normal mice, respectively. but hair growth activity of control group was not observed. After application of fractions of fresh Pinelliae Rhizoma extracts for 10 days, hair follicles of chloroform fraction treated group was observed middle stage of anagen phase and hair follicle were grown down to subcutaneous tissue of skin in all the mice. But hair follicles of initial stage of anagen phase were observed in water and ethyl acetate fractions. Most of hair follicles of telogen phase was observed in skin of control group. These experiments suggest that extracts of fresh Pinelliae Rhizoma may stimulate the topical hair growth activity and its chloroform fractions can be useful for treatment of alopecia areata.

• Natural Product Sciences
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• 제29권1호
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• pp.31-37
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• 2023

In this study, we investigated the efficacy of Celtis choseniana Nakai (C. choseniana) as complementary herbal medicine to ameliorate androgenic alopecia (AGA). The effects of C. choseniana on AGA were evaluated using testosterone propionate-induced AGA mouse model and dihydrotestosterone-treated human hair follicle dermal papilla cells. In vivo, C. choseniana treatment deactivated androgen signaling by reducing the concentration of serum dihydrotestosterone level and expressions of 5α-reductase 2 and androgen receptor. Next, C. choseniana treatment increased the hair regrowth rate. Histological studies demonstrated that C. choseniana induced the anagen phase in testosterone propionate-induced AGA mouse model. Cellular proliferation was promoted by C. choseniana treatment via increasing the expression of proliferation factors, such as proliferating cell nuclear antigen and cyclin D1. Furthermore, C. choseniana treatment increased the expression of proteins related to the Wnt/β-catenin signaling pathway. In addition, dickkopf-1, a Wnt inhibitor, was downregulated with C. choseniana treatment. Likewise, C. choseniana treatment promoted cellular proliferation in vitro. This study demonstrated the inhibitory effect of C. choseniana on androgen-induced AGA. Moreover, C. choseniana induced activation of Wnt/β-catenin signaling, resulting in prolonged anagen and cellular proliferation. Therefore, we suggest that C. choseniana can be used as a therapeutic agent to alleviate AGA.

• 동의생리병리학회지
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• 제25권3호
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• pp.496-502
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• 2011

The present study was undertaken to investigate the effect of bee venom acupuncture therapy on the hair follicle growth by macroscopic, microscopic and immunohistochemical observation of skin 10 and 17 days after treatment. The results were as follows : Macroscopic hair follicle growth of 0.2 ml S.B.V. acupuncture treated group was more prominent than those of 0.1 ml S.B.V. acupuncture treated group and control group. Microscopic observation indicated that the hair follicle growth of control group reached anagen phase IV of hair growing cycle, and that of 0.1 ml and 0.2 ml S.B.V. acupuncture treated groups reached anagen phase VI and catagen, respectively. Immunohistochemical observations of the expression of various cytokines, enzymes and receptors in association with hair follicle cycle after local treatment of S.B.V. acupuncture therapy are as follows: Expression of fibroblast growth factor was more intense in epidermis and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than that of 0.1 ml S.B.V. acupuncture treated group and control group. Expression of epidermal growth factor was more intense in bulge and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than that of 0.1 ml S.B.V. acupuncture treated group and control group. Expression of c-kit receptor was more intense in epidermis, bulge and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than that of control group. Expression of vascular endothelial growth factor was more intense in epidermis, bulge and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than that of control group. Expression of protein kinase C-${\alpha}$ was more intense in epidermis, bulge and outer root sheath in 0.2 ml S.B.V. acupuncture treated group than control group. It is concluded that bee venom acupuncture therapy promoted the expression of various cytokines, enzymes and receptors related to the hair growth cycle for hair growth. This findings indicates that bee venom acupuncture therapy is applicable to the treatment of hair loss.

• Experimental and Molecular Medicine
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• 제50권12호
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• pp.5.1-5.15
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• 2018

Targeting hair follicle regeneration has been investigated for the treatment of hair loss, and fundamental studies investigating stem cells and their niche have been described. However, knowledge of stem cell metabolism and the specific regulation of bioenergetics during the hair regeneration process is currently insufficient. Here, we report the hair regrowth-promoting effect of a newly synthesized novel small molecule, IM176OUT05 (IM), which activates stem cell metabolism. IM facilitated stemness induction and maintenance during an induced pluripotent stem cell generation process. IM treatment mildly inhibited mitochondrial oxidative phosphorylation and concurrently increased glycolysis, which accelerated stemness induction during the early phase of reprogramming. More importantly, the topical application of IM accelerated hair follicle regeneration by stimulating the progression of the hair follicle cycle to the anagen phase and increased the hair follicle number in mice. Furthermore, the stem cell population with a glycolytic metabotype appeared slightly earlier in the IM-treated mice. Stem cell and niche signaling involved in the hair regeneration process was also activated by the IM treatment during the early phase of hair follicle regeneration. Overall, these results show that the novel small molecule IM promotes tissue regeneration, specifically in hair regrowth, by restructuring the metabolic configuration of stem cells.

• 한방안이비인후피부과학회지
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• 제15권1호
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• pp.96-126
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• 2002

In the course of screening natural extracts for hair growth, we found that the extract of dried root of Sophora flavescens has the prominent hair growth promoting effect. After topical application of Sophora flavescens extract to the back of C57BL/6 mice, the earlier conversion of telogen-to-anagen phase was induced. In addition, the Sophora flavescens extract revealed to possess potent inhibitory effect on $5{\alpha}$-reductase Ⅰ and Ⅱ activity. The growth of dermal papilla cells and mouse vibrissae hair follicle cultured in vitro, however, was not affected by Sophora flavescens extract treatment. RT-PCR analysis showed that Sophora flavescens extract induced mRNA levels of growth factors such as insulin-like growth factor-Ⅰ and keratinocyte growth factor in dermal papilla cells, suggesting hair growth promoting effect of Sophora flavescens extract is mediated through inhibition of $5{\alpha}$-reductase type Ⅱ activity and the regulation of growth factors in dermal papilla cells. Furthermore, Sophora flavescens extract also showed anti-bacterial effect on Propionibacterium acnes. These results suggest that Sophora flavescens can be used as a potent treatment agent for helping hair growth stimulation and acne inhibition.

• 문화기술의 융합
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• 제4권3호
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• pp.253-259
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• 2018

떫은감 자원은 전통적으로 다방면의 여러 조직학적 질병을 치료하고 모발 성장을 비롯한 다양한 생물학적 활성에 매우 높은 효과가 있음이 알려져 왔다. 본 연구는 대머리 패턴의 검은 쥐 모델에 유전적으로 입증된 떫은감 추출물에 대한 발모 및 탈모방지 효능을 알아보고자 하였다. 표준화된 제형을 사용하여 대조군, 떫은감 추출물(10 mg/mouse/day)과 양성대조군인 미녹시딜(2 %)을 매일 두번씩 모발이 성장할 때까지 매일 등 피부에 일정량씩 도포 투여하여 조사하였다. C57BL/ 6 Black 쥐에서 모발 성장 세대를 통해 모발 성장의 변화 패턴이 관찰되었다. 모발 존재 면적과 모발의 길이는 처리 대조군 마우스 보다 떫은감 처리 마우스 처리구에서 유의하게 증가 하였다 (P>0.001). 또한 조직학적 평가에서도 대조군과 비교하여 떫은감 추출물의 처리구에서 모낭세포의 숫자가 현저하게 증가하였다. 따라서 본 실험 결과를 통하여 떫은감 추출물을 피부 도포시 누드 마우스의 모발 성장을 촉진하고 모발의 존재 영역을 확장시키고 모발 길이를 증가시켜 장기 모발 성장기의 지표가 될 수 있음을 알 수 있었다.

• 동의생리병리학회지
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• 제18권2호
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• pp.561-570
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• 2004

To screen the effective materials for hair loss treatment, the Gamissanghwa-tang extracts were tested. As a result we found that the Gamissanghwa-tang extracts have the hair growth promoting effect. After topical application of each test materials to the back of CS7BL/6 mice, the earlier conversion of telogen-to-anagen phase was induced. In the experiments of 5α-reductase type II inhibition assay, Radix Paeoniae Alba, Semen Cuscutae showed effective potential to inhibit the activity of 5α-reductase type II. And hair growth index of the Gamissanghwa-tang extracts ranked as 1.2, especially the hair growth index of Fructus Rubi is highest as 1.8. But there were no plant extracts which have effect on the DNA proliferation of hair dermal papilla cell measured by [³H]thymidine incorporation, the expression of growth factors such as IGF-I, KGF, HGF estimated by RT-PCR and protein synthesis of vibrissae hair follicle measured by [/sup 35/S] cysteine incorporation. Cortex Cinnamomi showed anti-bacterial effect on P. ovale, Radix Paeoniae Alba has the highest radical scavening activity and Radix Glycyrrhizae has the highest effects of NO synthesis. These results suggest that Gamissanghwa-tang can be used as a potent treatment agent for helping hair growth stimulation.

• Journal of Microbiology and Biotechnology
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• 제25권3호
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• pp.407-412
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• 2015

We investigated the effect of ultra-high molecular weight poly-γ-glutamic acid (UHMW γ-PGA) on hair loss in vitro and in vivo. 5-Alpha reductase is an enzyme that metabolizes the male hormone testosterone into dihydrotestosterone. By performing an in vitro experiment to analyze the inhibitory effects of UHMW γ-PGA on 5-alpha reductase activity, we determined that UHMW γ-PGA did in fact inhibit 5-alpha reductase activity, indicating the use of UHMW γ-PGA as a potential 5-alpha reductase inhibitor in the treatment of men with androgenetic alopecia. To evaluate the promotion of hair growth in vivo, we topically applied UHMW γ-PGA and minoxidil on the shaved dorsal skin of telogenic C57BL/6 mice for 4 weeks. At 4 weeks, the groups treated with UHMW γ-PGA showed hair growth on more than 50% of the shaved skin, whereas the control group showed less hair growth. To investigate the progression of hair follicles in the hair cycle, hematoxylin and eosin staining was performed. Histological observations revealed that the appearance of hair follicles was earlier in the UHMW γ-PGA-treated group than in the control group. The number of hair follicles on the relative area of shaved skin in the UHMW γ-PGA-treated group was higher than that observed on the shaved skin in the control group. These results indicate that UHMW γ-PGA can promote hair growth by effectively inducing the anagen phase in telogenic C57BL/6 mice.