Alpha-Mangostin: A Potent Inhibitor of TRPV3 and Pro-Inflammatory Cytokine Secretion in Keratinocytes

Int J Mol Sci. 2023 Aug 18;24(16):12930. doi: 10.3390/ijms241612930.

Abstract

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis.

Keywords: TRPV3; alpha-mangostin; dermatitis; keratinocytes; skin inflammation.

MeSH terms

  • Cytokines
  • Humans
  • Inflammation / drug therapy
  • Keratinocytes*
  • Skin*
  • TRPV Cation Channels / genetics

Substances

  • mangostin
  • Cytokines
  • TRPV3 protein, human
  • TRPV Cation Channels