2. Academic Validation
  3. Paeoniflorin protected UVA-exposed skin fibroblasts from caspase-3/GSDME mediated pyroptosis

Paeoniflorin protected UVA-exposed skin fibroblasts from caspase-3/GSDME mediated pyroptosis

  • J Photochem Photobiol B. 2025 Aug:269:113188. doi: 10.1016/j.jphotobiol.2025.113188.
Dongxin Shi 1,  Haitao Chu 2,  Yijun Sun 3,  Hailun He 4,  Wenyue Huang 3,  Hua Pan 5,  Cong Ma 6,  Shulan Yao 7,  Meihui Shi 4,  Hexiao Wang 8,  Yan Wu 9
Affiliations

Affiliations

  • 1 National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China; Department of Dermatology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
  • 2 National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China; Department of Hyperbaric Oxygen, The First Hospital of China Medical University, Shenyang, China.
  • 3 National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China; Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.
  • 4 National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China.
  • 5 Department of Dermatology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
  • 6 National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China; Department of Dermatology, The Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, China.
  • 7 National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China; Department of Dermatology, Affiliated Hospital of Jining Medical University, Jining, China; Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China.
  • 8 National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China. Electronic address: 1106525287@qq.com.
  • 9 National joint Engineering Research Center for Theranostics of Immunological Skin Diseases, The First Hospital of China Medical University and Key Laboratory of Immunodermatology, Ministry of Health and Ministry of Education, Shenyang, China; Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang, China. Electronic address: jlwuyan@126.com.
PMID: 40466282 DOI: 10.1016/j.jphotobiol.2025.113188
Abstract

Background: UVA radiation can impact fibroblasts and leads to alterations in dermal connective tissue. Pyroptosis is a form of regulated cell death characterized by gasdermin-mediated membrane pore formation and release of intracellular contents. Whether UVA exposure can trigger Pyroptosis in fibroblasts is unclear. Paeoniflorin has antioxidant properties, but whether it alleviates Pyroptosis through inhibiting oxidative stress in fibroblasts is not yet determined.

Objectives: To identify the occurrence and the molecular mechanism of cell Pyroptosis in skin fibroblasts, and explore the anti-pyroptotic effect of paeoniflorin in UVA induced photodamage protection.

Methods: Using Human skin fibroblasts (HSFs), wild-type primary human dermal fibroblasts (HDFs) and CASP3 knockdown HDFs, we analyzed the occurrence of Pyroptosis by examining changes in morphology, LDH release and the expression of pyroptotic molecules after UVA radiation. UVA-exposed C57BL/6 mice and human sun-exposed skin samples were used to analyze the expression of Caspase-3/GSDME. The role of oxidative stress was investigated by using NAC. Paeoniflorin treatment was analyzed for its effects on Pyroptosis and the expression of Caspase-3/GSDME.

Results: Both HSFs and HDFs exposed to UVA exhibited dose-dependent Pyroptosis. In HDFs, UVA increased the expression of Caspase-3, GSDME, PARP, caspase-9, Cytochrome C, Bax/Bcl-2, while the expression of NLRP3, Caspase-1, caspase-4, GSDMD was not significantly changed. UVA-exposed C57BL/6 mice and human sun-exposed skin samples showed increased Caspase-3/GSDME. Treatment of NAC or paeoniflorin suppressed UVA-induced Pyroptosis and mitochondrial-mediated Apoptosis.

Conclusions: UVA induced Caspase-3/GSDME mediated Pyroptosis in both HSFs and HDFs, and paeoniflorin protected against UVA induced photodamage by suppressing this pathway.

Keywords

Apoptosis; GSDME; Paeoniflorin; Pyroptosis; Skin aging; Ultraviolet rays.

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