Hye-In Choi1, Dong Young Kim2, Soon-Jin Choi1, Chang-Yup Shin1, Sungjoo Tommy Hwang3, Kyu Han Kim2, Ohsang Kwon4. 1. Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human Environment Interface Biology, Seoul National University College of Medicine, Seoul, Republic of Korea. 2. Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human Environment Interface Biology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea. 3. Dr. Hwang's Hair-Hair Clinic, Seoul, Republic of Korea. 4. Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea; Institute of Human Environment Interface Biology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: oskwon@snu.ac.kr.
Abstract
BACKGROUND: Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, increases the intracellular level of cyclic adenosine monophosphate to cause vasodilation. Topical application of cilostazol is reported to improve local blood flow and enhance wound healing; however, its effect on human hair follicles is unknown. OBJECTIVE: The purpose of this study was to determine the effect of cilostazol on hair growth. METHODS: We investigated the expression of PDE3 in human dermal papilla cells (DPCs), outer root sheath cells (ORSCs), and hair follicles. The effects of cilostazol on DPC and ORSC proliferation were evaluated using BrdU and WST-1 assays. The expression of various growth factors in DPCs was investigated by growth factor antibody array. Additionally, hair shaft elongation was measured using ex vivo hair follicle organ cultures, and anagen induction was evaluated in C57BL/6 mice. Finally, the effects of cilostazol on vessel formation and activation of the mitogen-activated protein kinase pathway were evaluated. RESULTS: We confirmed high mRNA and protein expression of PDE3 in human DPCs. Cilostazol not only enhanced the proliferation of human DPCs but also regulated the secretion of several growth factors responsible for hair growth. Furthermore, it promoted hair shaft elongation ex vivo, with increased proliferation of matrix keratinocytes. Cilostazol also accelerated anagen induction by stimulating vessel formation and upregulating the levels of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase, and P38 after its topical application in C57BL/6 mice. CONCLUSION: Our results show that cilostazol promotes hair growth and may serve as a therapeutic agent for the treatment of alopecia.
BACKGROUND:Cilostazol, a phosphodiesterase 3 (PDE3) inhibitor, increases the intracellular level of cyclic adenosine monophosphate to cause vasodilation. Topical application of cilostazol is reported to improve local blood flow and enhance wound healing; however, its effect on human hair follicles is unknown. OBJECTIVE: The purpose of this study was to determine the effect of cilostazol on hair growth. METHODS: We investigated the expression of PDE3 in human dermal papilla cells (DPCs), outer root sheath cells (ORSCs), and hair follicles. The effects of cilostazol on DPC and ORSC proliferation were evaluated using BrdU and WST-1 assays. The expression of various growth factors in DPCs was investigated by growth factor antibody array. Additionally, hair shaft elongation was measured using ex vivo hair follicle organ cultures, and anagen induction was evaluated in C57BL/6 mice. Finally, the effects of cilostazol on vessel formation and activation of the mitogen-activated protein kinase pathway were evaluated. RESULTS: We confirmed high mRNA and protein expression of PDE3 in human DPCs. Cilostazol not only enhanced the proliferation of human DPCs but also regulated the secretion of several growth factors responsible for hair growth. Furthermore, it promoted hair shaft elongation ex vivo, with increased proliferation of matrix keratinocytes. Cilostazol also accelerated anagen induction by stimulating vessel formation and upregulating the levels of phosphorylated extracellular signal-regulated kinase, c-Jun N-terminal kinase, and P38 after its topical application in C57BL/6 mice. CONCLUSION: Our results show that cilostazol promotes hair growth and may serve as a therapeutic agent for the treatment of alopecia.
Authors: Helmy Moawad; Sally A El Awdan; Nada A Sallam; Wafaa I El-Eraky; Mohammed A Alkhawlani Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2019-08-01 Impact factor: 3.000