The skin photoprotective effect of trilinolein: Induction of cellular autophagy via the AMPK-mTOR signaling pathway.

Trilinolein (TL) is an active substance contained in traditional Chinese herbs; modern studies have shown that trilinolein has anti-inflammatory and antioxidant effects on the body. This study delves into the photoprotective effect of trilinolein on UVB-irradiated Human Skin Fibroblast (HSF) cells and the underlying mechanisms. Our findings reveal that trilinolein had a photoprotective effect on HSF cells: trilinolein enhanced cellular autophagy, restored UVB-inhibited cell proliferative viability, and curbing UVB-induced reactive oxygen species (ROS) and apoptosis. Intriguingly, after inhibition of TL-induced autophagy via wortmannin, diminished trilinolein's photoprotective effects. Meanwhile, trilinolein was shown to modulate the AMPK-mTOR signaling pathway, thus enhance cellular autophagy in HSF cells, and this tendency was suppressed after the administration of compound C (AMPK inhibitor). In a mouse model of skin photodamage, trilinolein significantly mitigated photodamage extent through morphological and histopathological analyses. This study illuminates trilinolein could inhibit the photodamaging effects of UVB irradiation by regulating cellular autophagy through the AMPK-mTOR signaling pathway, suggesting its promising application in combating UV-induced skin disorders.

Kangfuxin liquid reduces the ultraviolet B-induced photodamage of HaCaT cells by regulating autophagy.

Kangfuxin liquid (KFX), an extract of the American cockroach, has been clinically proven to be effective in various skin damage disorders, but there are no reports on its use in photodamage. We explored the effect of KFX on ultraviolet B (UVB)-induced photodamage and whether its mechanism was related to autophagy. We found that KFX treatment reduced UVB-induced reactive oxygen species production and improved the vitality of cells inhibited by UVB irradiation. The expression of LC3 (A/B), which was inhibited after UVB irradiation, could be rescued by KFX treatment. Furthermore, KFX may upregulate the level of cellular autophagy by regulating the AMPK-mTOR signaling pathway. When the autophagy inhibitor wortmannin was used to inhibit autophagy, the protective effect of KFX on cells was diminished or even disappeared. Our study suggests that KFX may resist UVB-mediated oxidative stress damage of HaCaT through the induction of autophagy.

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

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.

Handelin Reduces Ultraviolet A-Induced Photoaging by Inhibiting Reactive Oxygen Species Generation and Enhancing Autophagy.

Photoaging is mainly caused by the exposure of the skin to ultraviolet (UV) radiation. Among them, damage to human dermal fibroblast (HDF) cells caused by ultraviolet A (UVA) is the main cause of skin aging. Researchers have dedicated to identifying natural compounds from plants to fight against UV radiation-induced photoaging. We previously found that extracts from wild chrysanthemum could prevent acute damage and photoaging induced by UV irradiation. As one of the most abundant ingredients in wild chrysanthemum extract, handelin was hypothesized to have the potential to prevent UVA-induced photoaging of skin fibroblast. In the present study, we report the great potential of handelin in combating UVA-induced photoaging of fibroblasts. We firstly demonstrated that handelin was safe for skin fibroblast as high as a concentration of 0.0125 µM, showing no toxicity on the cells and improved cell viability. Furthermore, handelin can reduce UVA-induced cellular senescence, indicated by a reduced proportion of senescence-associated beta-galactose positive cells and the expression of P21. We then verified that handelin pretreatment markedly attenuated the production of reactive oxygen species (ROS) generation after UVA irradiation. Meanwhile, we found that handelin enhances autophagy after UVA irradiation, and autophagy is involved in the quality control of intracellular proteins after UV-induced damage (partially indirectly via ROS). Therefore, these results suggest that handelin has a very high potential as an effective ingredient against UVA-induced skin aging. Moreover, this provides an important basis for further research on the photoprotective mechanism of handelin.

First-Principles Study on Self-Activated Luminescence and 4f → 5d Transitions of Ce3+ in M5(PO4)3X (M = Sr, Ba; X = Cl, Br).

The origin of the self-activated luminescence in the apatite-type M5(PO4)3X (MPOX; M = Sr or Ba; X = Cl or Br) samples and the spectral assignment for cerium-doped Sr5(PO4)3Cl (SPOC) phosphors are determined from first-principles methods combined with hybrid density functional theory (DFT) calculations, using the standard PBE0 hybrid functional, with wave function-based embedded-cluster ab initio calculations (at the CASSCF/CASPT2/RASSI-SO level). Electronic structure calculations are performed in order to accurately derive the band gaps of the hosts, the locations of impurity states in the energy bands that are caused by native defects and doped Ce3+ ions, and the charge-compensation mechanisms of aliovalent doping. The calculations of defect formation energies under O-poor conditions demonstrate that the native defects are easily generated in the undoped MPOX samples prepared under reducing atmospheres, from which thermodynamic and optical transition energy levels, as well as the corresponding energies, are derived in order to interpret the luminescence mechanisms of the undoped MPOX as previously reported. Our calculations reveal that the self-activated luminescence is mainly attributed to the optical transitions of the excitons bound to the oxygen vacancies (VO), along with their transformation of the charge states 0 ↔ 1+. Furthermore, the eight excitation bands observed in the synchrotron radiation excitation spectra of SPOC: Ce3+, Na+ phosphors are successfully assigned according to the ab initio calculated energies and relative oscillator strengths of the 4f1 → 5d1-5 transitions for the Ce3+ ions at both the Sr(1) and Sr(2) sites in the host. It is hoped that the feasible first-principles approaches in this work are applied in order to explore the origins of the luminescence in undoped and lanthanide-doped phosphors, complementing the experiments from the perspective of chemical compositions and the microstructures of materials.