Kang Myung-Gyun, Park Daeui, Han Hyoung-Yun, Shim Hyeeun, Hong Yoonjung, Moon Jiyeon, Yoon Seokjoo, Kwon Bosun
Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon, Korea.
Research Institute, Wooridul Huebrain Ltd., Seoul, Korea.
Ann Dermatol. 2019 Oct;31(5):530-537. doi: 10.5021/ad.2019.31.5.530. Epub 2019 Aug 30.
Androgenic alopecia (AGA) is the most common type of hair loss. It is likely inherited genetically and is promoted by dihydrotestosterone. 5α-reductase has been proven a good target through finasteride use. However, the pathogenesis of AGA cannot be fully explained based only on dihydrotestosterone levels.
To identify similar hairloss inhibition activity of RE-ORGA with mode of action other than finasteride.
We prepared RE-ORGA from Korean herb mixtures. We performed MTT assays for cytotoxicity, Cell Counting Kit-8 assays for cell proliferation, and western blot to identify expression levels of 5α-reductase and Bax. RNA-sequencing was performed for the expression patterns of genes in dihydrotestosterone-activated pathways. Anti-inflammatory activity was also assessed by the expression levels of tumor necrosis factor-alpha (TNF-α) and interleukin 6.
REORGA could promote the proliferation of human dermal papilla cells and showed low cytotoxicity. It also inhibited the expression of 5α-reductases and Bax in the cells. RNA-sequencing results verified that the mRNA expressions of , Bax, transforming growth factor-beta 1 (TGF-β1), and TGF-β1 induced transcript 1 (TGFβ1I1) were decreased, whereas expression of protein tyrosine kinase 2 beta (PTK2β) was more elevated. REORGA also showed anti-inflammatory activity through decreased mRNA levels of TNF-α.
Transcriptionally, up-regulation of PTK2β and concomitant down-regulation of TGFβ1I1 imply that RE-ORGA can modulate androgen receptor sensitivity, decreasing the expression of 5α-reductase type II and Bax together with TGF-β1 transcripts; RE-ORGA also showed partial anti-inflammatory activity. Overall, RE-ORGA is expected to alleviate hair loss by regulating 5α-reductase activity and the receptor's androgen sensitivity.
雄激素性脱发（AGA）是最常见的脱发类型。它可能由遗传因素导致，并受二氢睾酮影响。通过使用非那雄胺，已证实5α-还原酶是一个有效的靶点。然而，仅基于二氢睾酮水平并不能完全解释AGA的发病机制。
确定RE - ORGA具有不同于非那雄胺作用方式的类似脱发抑制活性。
我们从韩国草药混合物中制备了RE - ORGA。我们进行了MTT细胞毒性试验、细胞计数试剂盒-8细胞增殖试验以及蛋白质免疫印迹法以鉴定5α-还原酶和Bax的表达水平。对二氢睾酮激活途径中的基因表达模式进行了RNA测序。还通过肿瘤坏死因子-α（TNF-α）和白细胞介素6的表达水平评估了抗炎活性。
REORGA可促进人真皮乳头细胞的增殖，且细胞毒性较低。它还抑制细胞中5α-还原酶和Bax的表达。RNA测序结果证实，Bax、转化生长因子-β1（TGF-β1）和TGF-β1诱导转录物1（TGFβ1I1）的mRNA表达降低，而蛋白酪氨酸激酶2β（PTK2β）的表达升高。REORGA还通过降低TNF-α的mRNA水平表现出抗炎活性。
在转录水平上，PTK2β的上调和TGFβ1I1的下调意味着RE - ORGA可以调节雄激素受体敏感性，同时降低II型5α-还原酶、Bax以及TGF-β1转录物的表达；RE - ORGA还表现出部分抗炎活性。总体而言，RE - ORGA有望通过调节5α-还原酶活性和受体的雄激素敏感性来减轻脱发。
