2. Academic Validation
  3. Handelin protects human skin keratinocytes against ultraviolet B-induced photodamage via autophagy activation by regulating the AMPK-mTOR signaling pathway

Handelin protects human skin keratinocytes against ultraviolet B-induced photodamage via autophagy activation by regulating the AMPK-mTOR signaling pathway

  • Arch Biochem Biophys. 2023 Jul 15:743:109646. doi: 10.1016/j.abb.2023.109646.
Jimin Chu 1,  Yang Xiang 2,  Xianghong Lin 1,  Miao He 3,  Yan Wang 4,  Qiong Ma 4,  Jingxian Duan 4,  Sujiao Sun 5
Affiliations

Affiliations

  • 1 School of Clinical Medicine, Dali University, Dali, 671000, Yunnan, China.
  • 2 Metabolic Control and Aging, Human Aging Research Institute (HARI), Jiangxi Key Laboratory of Human Aging, School of Life Science, Nanchang University, Nanchang, 330031, Jiangxi, China.
  • 3 School of Pharmacy, Dali University, Dali, 671013, Yunnan, China.
  • 4 Medical Cosmetology Teaching and Research Section, School of Clinical Medicine, Dali University, Dali, 671000, Yunnan, China.
  • 5 Medical Cosmetology Teaching and Research Section, School of Clinical Medicine, Dali University, Dali, 671000, Yunnan, China. Electronic address: [email protected].
PMID: 37225010 DOI: 10.1016/j.abb.2023.109646
Abstract

Handelin is a natural ingredient extracted from Chrysanthemum boreale flowers that has been shown to decrease stress-related cell death, prolong lifespan, and promote anti-photoaging. However, whether handelin inhibits ultraviolet (UV) B stress-induced photodamage remains unclear. In the present study, we investigate whether handelin has protective properties on skin keratinocytes under UVB irradiation. Human immortalized keratinocytes (HaCaT keratinocytes) were pretreated with handelin for 12 h before UVB irradiation. The results indicated that handelin protects keratinocytes against UVB-induced photodamage by activating Autophagy. However, the photoprotective effect of handelin was suppressed by an autophagic inhibitor (wortmannin) or the transfection of keratinocytes with a small interfering RNA targeting ATG5. Notably, handelin reduced mammalian target of rapamycin (mTOR) activity in UVB-irradiated cells in a manner similar to that shown by the mTOR Inhibitor rapamycin. Adenosine monophosphate-activated protein kinase (AMPK) activity was also induced by handelin in UVB-damaged keratinocytes. Finally, certain effects of handelin, including Autophagy induction, mTOR activity inhibition, AMPK activation, and reduction of cytotoxicity, were suppressed by an AMPK Inhibitor (compound C). Our data suggest that handelin effectively prevents photodamage by protecting skin keratinocytes against UVB-induced cytotoxicity via the regulation of AMPK/mTOR-mediated Autophagy. These findings provide novel insights that can aid the development of therapeutic agents against UVB-induced keratinocyte photodamage.

Keywords

AMPK; Autophagy; Handelin; Photodamage; UVB; mTOR.

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