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Inhibitory effects of bioactive compounds on UVB-induced photodamage in human keratinocytes: modulation of MMP1 and Wnt signaling pathways

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Abstract

UVB radiation significantly threatens skin health, contributing to wrinkle formation and an elevated risk of skin cancer. This study aimed to explore bioactive compounds with potential UVB-protective properties. Using in silico analysis, we chose compounds to reduce binding energy with matrix metalloproteinase-1 (MMP1). Piperitoside, procyanidin C1, and mulberrofuran E emerged as promising candidates through this computational screening process. We investigated the UVB-protective efficacy of the selected compounds and underlying mechanisms in human immortalized keratinocytes (HaCaT). We also investigated the molecular pathways implicated in their action, focusing on the transforming growth factor (TGF)-β and wingless-related integration site (Wnt)/β-catenin signaling pathways. In UVB-exposed HaCaT cells (100 mJ/cm2 for 30 min), piperitoside, procyanidin C1, and mulberrofuran E significantly reduced reactive oxygen species (ROS) and lipid peroxides, coupled with an augmentation of collagen expression. These compounds suppressed MMP1, tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) expression, while they concurrently enhanced collagen-1 (COL1A1), β-catenin (CTNNB1), and superoxide dismutase type-1 (SOD1) expression. Furthermore, Wnt/β-catenin inhibitors, when administered subsequently, partially counteracted the reduction in MMP1 expression and alleviated inflammatory and oxidative stress markers induced by the bioactive compounds. In conclusion, piperitoside, procyanidin C1, and mulberrofuran E protected against UVB-induced damage in HaCaT cells by inhibiting MMP1 expression and elevating β-catenin expression. Consequently, these bioactive compounds emerge as promising preventive agents for UVB-induced skin damage, promoting skin health.

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Data availability

The data presented in this study are available upon request from the corresponding author.

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Funding

This research was supported by the National Research Foundation in Korea (RS-2023-00208567).

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Author notes

  1. Meiling Liu and Shaokai Huang have equal contribution.

Authors and Affiliations

  1. Department of Chemical Engineering, Shanxi Institute of Science and Technology, Jincheng, 048011, China

    Meiling Liu

  2. Department of Bioconvergence, Hoseo University, Asan, 31499, Korea

    Shaokai Huang

  3. Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, 165 Sechul-Ri, BaeBang-Yup, Asan-Si, ChungNam-Do, 336-795, South Korea

    Sunmin Park

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Contributions

Conceptualization and methodology, SP and ML; formal analysis, SH and ML; writing—original draft preparation, ML; writing—review and editing, SP; funding acquisition, SP; all the authors have read and agreed to the published version of the manuscript.

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Correspondence to Sunmin Park.

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Supplementary Information

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43630_2023_531_MOESM1_ESM.pdf

Supplementary file1 Table S1. Primer lists of superoxide dismutase-1 (SOD1), iNOS, β-catenin, MMP1, TNF-α, and collagen1 genes. Figure S1. Molecular docking of MMP1 with Physalin O (A) and Mangicrocin (B). Molecular docking of Physalin O or Mangicrocin with MMP1 (1) Cartoon representation of food component (balls and stick model) binding with MMP1, (2) binding of food component at the central cavity of MMP1, and (3) 2D depiction of MMP1 interacting with food component and the nature of forces involved in stabilizing MMP1 – (+)-food component. Figure S2. Reactive oxygen species (ROS), lipid peroxides and mRNA expression of oxidative stress and inflammation-related proteins after pretreatment of SB431542: a selective and potent inhibitor of the TGF-β/Activin/NODAL pathway. A. ROS contents. B. Lipid peroxide contents. C. mRNA expression of Collagen 1. D. mRNA expression of MMP1. E. mRNA expression of TNF-α. F. mRNA expression of SOD1. G. mRNA expression of iNOS. H. mRNA expression of β-catenin (PDF 832 KB)

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Liu, M., Huang, S. & Park, S. Inhibitory effects of bioactive compounds on UVB-induced photodamage in human keratinocytes: modulation of MMP1 and Wnt signaling pathways. Photochem Photobiol Sci 23, 463–478 (2024). https://doi.org/10.1007/s43630-023-00531-0

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