Isatis tinctoria L. Leaf Extract Inhibits Replicative Senescence in Dermal Fibroblasts by Regulating mTOR-NF-κB-SASP

Jieun Woo1, Seoungwoo Shin1, Hyanggi Ji1

  • 1BioSpectrum Life Science Institute, 767, Sinsu-ro, Yongin-si 16827, Korea.

Nutrients
|May 14, 2022
PubMed

Insights

Isatis tinctoria L. leaf extract (ITE) combats skin aging by inhibiting senescence-associated secretory phenotype (SASP) factors. This senomorphic approach targets the mTOR-NF-κB pathway, reducing inflammation and restoring skin health.

Area of Science:

  • Dermatology and Cellular Biology
  • Aging Research
  • Pharmacology

Background:

  • Cellular senescence, characterized by senescence-associated secretory phenotype (SASP) factors, drives skin aging.
  • Targeting SASP regulation represents a novel therapeutic strategy for aging.
  • Senescent fibroblasts impair skin tissue function.

Purpose of the Study:

  • To investigate the senomorphic effects of Isatis tinctoria L. leaf extract (ITE) on human dermal fibroblasts.
  • To determine if ITE inhibits senescence biomarkers (p53, p21, p16) and SASP secretions.
  • To elucidate the molecular pathways targeted by ITE in cellular senescence.

Main Methods:

  • Assessed ITE's impact on senescence biomarkers (p53, p21, p16) gene expression in replicative senescent human dermal fibroblasts (RS-HDF).
  • Quantified SASP factor secretion inhibition by ITE.
  • Investigated ITE's effects on the mTOR, MAPK, and NF-κB signaling pathways, including protein phosphorylation and nuclear translocation.
  • Explored the role of the autophagy pathway in ITE's anti-senescence activity.

Main Results:

  • ITE effectively inhibited the expression of senescence biomarkers p53, p21, and p16.
  • ITE suppressed the secretion of SASP factors from RS-HDFs.
  • ITE regulated the MAPK/NF-κB pathway by inhibiting mTOR, MAPK, and IκBα phosphorylation, and blocking NF-κB nuclear translocation.
  • The autophagy pathway was implicated in ITE's inhibitory effect on cellular senescence.

Conclusions:

  • ITE demonstrates senomorphic properties by preventing and restoring cellular senescence in human dermal fibroblasts.
  • ITE acts through the regulation of the mTOR-NF-κB pathway to inhibit the activation and secretion of senescence-related factors.
  • ITE holds potential as a therapeutic agent for age-related skin conditions by targeting cellular senescence and inflammation.

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