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Publications

Journal Article Epublish

PubMed: 40710517 DOI: 10.3390/md23070292

A Marine-Derived Steroid from Rhodococcus sp., 3,12-Dioxochola-4,6-dien-24-oic Acid, Enhances Skin Re-Epithelialization and Tissue Repair.

Mar Drugs 23(7)

Authors: Mücahit Varlı, Hui Tan, Chaeyoung Lee, Jeongyun Lee, Ji Young Lee, Jeong-Hyeon Kim, Songyi Lee, Hangun Kim, Sang-Jip Nam

Affiliations

  • College of Pharmacy, Sunchon National University, Sunchon 57922, Republic of Korea.
  • Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.
  • Institute of Sustainable Earth and Environmental Dynamics (SEED), Pukyong National University, 365 Sinseon-ro, Nam-gu, Busan 48547, Republic of Korea.
  • Department of Chemistry, Pukyong National University, Busan 48513, Republic of Korea. Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan 48513, Republic of Korea.
  • Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea. Graduate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul 03760, Republic of Korea.

Abstract

The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion and migration. It upregulated key growth factors (EGF, VEGF-A, IGF, TGF-β, and HGF), indicating the activation of regenerative signaling. Additionally, DOCDA increased the expression of genes related to focal adhesion and cytoskeletal regulation (ITGB1, ITGA4, FAK, SRC, RHOA, CDC42, RAC1, and paxillin), supporting enhanced cellular motility and remodeling. Notably, DOCDA promoted stem-like properties in HaCaT cells, as shown by increased spheroid formation and elevated levels of the stemness markers ALDH1 and CD44. Target prediction and molecular docking identified the glucocorticoid receptor (GR) as the primary target of DOCDA, with a docking score of -7.7 kcal/mol. Network and pathway enrichment analysis revealed that GR-linked pathways were significantly associated with wound healing, including steroid hormone signaling, inflammation, immune responses, and cell migration. In vivo, the topical application of DOCDA led to over 70% wound closure in mice by day 5. These findings suggest that DOCDA is a steroid-like compound that accelerates wound healing and may serve as a potential agent in regenerative therapy.

MeSH

Re-Epithelialization, Skin, Cells, Vascular Endothelial Growth Factor A, Microscopy, Electron, Scanning Transmission, Pharmaceutical Preparations, Receptors, Glucocorticoid, Rhodococcus, Tissues, Steroids