Biomolecules & Therapeutics

  • 제33권1호
  • /
  • Pages.210-220
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  • 2025
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Tanshinone, a Natural NADPH Oxidase Inhibitor, Mitigates Testosterone-Induced Hair Loss

  • Yeo Kyu Hur (Department of Life Sciences, Ewha Womans University) ;
  • Jin Yeong Chae (Department of Life Sciences, Ewha Womans University) ;
  • Min Hye Choi (Department of Life Sciences, Ewha Womans University) ;
  • Kkotnara Park (Department of Life Sciences, Ewha Womans University) ;
  • Da-Woon Bae (Department of Chemistry and Nanoscience, Ewha Womans University) ;
  • Soo-Bong Park (Department of Chemistry and Nanoscience, Ewha Womans University) ;
  • Sun-Shin Cha (Department of Chemistry and Nanoscience, Ewha Womans University) ;
  • Hye Eun Lee (Celros Biotech) ;
  • In Hye Lee (Department of Life Sciences, Ewha Womans University) ;
  • Yun Soo Bae (Department of Life Sciences, Ewha Womans University)
  • 투고 : 2024.06.09
  • 심사 : 2024.08.13
  • 발행 : 2025.01.01
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초록

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H2O2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

키워드

과제정보

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) [RS-2024-00398295 to Y.S.B, NRF-2022R1A2C3006924 to S.-S.C., and NRF-2021R1A2C109 1259 to I.H.L.] and by the Starting growth Technological R&D Program (20165925) funded by the Ministry of SMEs and Startups (MSS, Korea).

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