Kaempferol tetrasaccharides restore skin atrophy via PDK1 inhibition in human skin cells and tissues: Bench and clinical studies

Juewon Kim, Hyung Su Kim, Dong Hwa Choi, Jiwon Choi, Sung Yeon Cho, Seung Hun Kim, Heung Soo Baek, Kee Dong Yoon, Sang Wook Son, Eui Dong Son, Yong Deog Hong, Jaeyoung Ko, Si Young Cho, Won Seok Park

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)

Abstract

Skin aging is a major risk factor for the dermal diseases, and interventions to attenuate cellular senescence are expected to reduce the risk for age-related diseases involving skin atrophy. However, blocking cell death or extending proliferation causally results in side effects and an increased cancer risk. For identification of a safer approach, we focused on PDK1 inhibition, which could revert cellular senescence and reduce senescence factors in skin in vitro, in a human skin equivalent model and in an exploratory, placebo-controlled, interventional trial. Natural phytochemical kaempferol tetrasaccharides resulted in a significant reduction in cellular senescence, and an increase in collagen fiber was observed in the skin cell and human skin equivalent. Clinical enhancement in skin appearance was noted in multiple participants, and an immunohistochemical study revealed improvement in the histological appearance of skin tissue and extracellular matrix. This change was associated with relative improvement in histological markers of senescence and clinical appearance of the aged skin and an increase in collagen fiber, an essential factor for preventing skin atrophy and consistency of the basement membrane. These results indicate that PDK1 inhibition is a potentially effective antiaging intervention, suggesting a diagnostic role and preventive actions of PDK1 in senescence-associated skin atrophy.

Original languageEnglish
Article number113864
JournalBiomedicine and Pharmacotherapy
Volume156
DOIs
Publication statusPublished - 2022 Dec
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 The Authors

Keywords

  • AKT/NFĸB signaling
  • Cellular state
  • ECM breakdown
  • Kaempferol tetrasaccharide
  • PDK1
  • Skin atrophy

ASJC Scopus subject areas

  • Pharmacology

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