Botryocladia leptopoda Extracts Promote Wound Healing Ability via Antioxidant and Anti-Inflammatory Activities and Regulation of MMP/TIMP Expression

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Shin-Ping Lin, Tsung-Kai Yi, Yi-Feng Kao, Ming-Chieh Tu, Chen-Che Hsieh, Yu-Chieh Chou, Jheng-Jhe Lu, Shella Permatasari Santoso, Huey-Jine Chai, Kuan-Chen Cheng

2025 Marine Drugs Vol. 23 Issue 11 Article Cited by 1 Quartile

Abstract

Wound healing is a complex process involving coordinated actions of multiple cell types. Therefore, when developing therapeutics to promote wound healing, it is essential to consider the synergistic contributions of various cells at different stages of the healing process. In this study, we evaluated the potential of different extracts of Botryocladia leptopoda as wound-healing agents by examining their effects on antioxidant activity, cytotoxicity, cell migration, anti-inflammatory properties, and expressions of specific biomarkers associated with wound healing. Results indicated that the ethanol extract (FE) and hexane extract (HE) exhibited the highest DPPH radical scavenging activity, reaching up to 94%. The alkaline extract (AE) showed the strongest antioxidant ability in the FICA assay, with a maximum of 99%. In addition, the FE and AE provided anti-inflammatory actions that inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-6 in lipopolysaccharide (LPS)-treated RAW 264.7 cells. Further analyses suggested that the FE and AE enhanced cell proliferation (210% and 112%) and migration (442.2% and 535.6%) and regulated wound healing-related genes, including matrix metalloproteinase 2, MMP9, and tissue inhibitor of metalloproteinase 2 (TIMP2) to avoid scar formation and accelerate wound healing. Lastly, the identification of potential compounds within the extract using the UHPLC system further supports its prospective medical applications. Taken together, these findings indicated that the FE and AE from B. leptopoda exhibited remarkable in vitro wound-healing properties, highlighting their potential for applications in pharmaceutical industries and health food development. © 2025 by the authors.

Affiliations

School of Food Safety, Taipei Medical University, Taipei, 11031, Taiwan; Ph.D. Program in Drug Discovery and Development Industry, Taipei Medical University, Taipei, 11031, Taiwan; Research Center of Biomedical Device, Taipei Medical University, Taipei, 11031, Taiwan; Seafood Technology Division, Fisheries Research Institute, Ministry of Agriculture, Keelung, 20246, Taiwan; Department of Seafood Science, College of Hydrosphere, National Kaohsiung University of Science and Technology, Kaohsiung, 81157, Taiwan; Institute of Biotechnology, National Taiwan University, Taipei, 10617, Taiwan; Department of Chemical Engineering, Faculty of Engineering, Widya Mandala Surabaya Catholic University, Surabaya, 60114, Indonesia; Chemical Engineering Master Program, Widya Mandala Surabaya Catholic University, Surabaya, 60114, Indonesia; Collaborative Research Center for Zero Waste and Sustainability, Widya Mandala Surabaya Catholic University, Surabaya, 60114, Indonesia; Institute of Food Science and Technology, National Taiwan University, Taipei, 10617, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, 40402, Taichung, Taiwan; Department of Optometry, Asia University, Taichung, 41354, Taiwan; Department of Food Science, Fu Jen Catholic University, New Taipei City, 242062, Taiwan