Anti-Hair Loss Effects of the DP₂ Antagonist in Human Follicle Dermal Papilla Cells

• Published in: Cosmetics
• Main Authors: Hye Won Lim, Hyunwoo Joo, Chae Young Jeon, Yurim Lee, Mujun Kim, Jung Un Shin, Jinsick Kim, SoonRe Kim, Sanghwa Lee, Dong Chul Lim, Hee Dong Park, Byung Cheol Park, Dong Wook Shin
• Format: Article
• Language: English
• Published: MDPI AG 2024-10-01
• Subjects: DP₂ antagonist; human follicle dermal papilla cells; hair growth; hair loss; dihydrotestosterone
• Online Access: https://www.mdpi.com/2079-9284/11/5/177

Prostaglandin D₂ (PGD₂) levels are high in the balding areas of human scalps, and PGD₂ has been found to inhibit hair growth. It is known that the inhibition of the PGD₂ receptor can promote hair growth by preventing hair follicles from entering the catagen phase. Thus, we identified an antagonist of DP2, the receptor for PGD2, as a potential treatment for hair loss using an AI-based DeepZema^® drug development program. In this study, we identified that the DP₂ antagonist (DP2A) could ameliorate alopecia in human follicle dermal papilla cells (HFDPCs) that were stimulated by dihydrotestosterone (DHT), a known molecule related to hair loss. We observed that the DP2A promoted wound healing efficiency and increased alkaline phosphatase levels in the HFDPCs that were damaged with DHT. In addition, we found that the DP2A diminished the reactive oxygen species (ROS) levels generated in the DHT-damaged HFDPCs. We confirmed that the DP2A effectively recovered the membrane potential of mitochondria in these cells. We also demonstrated that the DP2A enhanced the phosphorylation levels of both Akt and ERK in the HFDPCs that were damaged with DHT. Notably, we revealed that the DP2A slightly enlarged the three-dimensional spheroid size in these cells and confirmed that the DP2A improved hair growth in the organ culture of human hair follicles. Taken together, we suggest that DP2A has therapeutic effects on HFDPCs that are damaged by DHT and holds promise as a potential treatment for treating hair loss.