Ananto Ali Alhasyimi, Alexander Patera Nugraha, Aulia Ayub, Trianna Wahyu Utami, Timothy Sahala Gerardo, Nuril Farid Abshori, Mohammad Adib Khumaidi, Trina Ekawati Tallei, Nurpudji Astuti Taslim, Bonglee Kim, Raymond Rubianto Tjandrawinata, Apollinaire Tsopmo, Fahrul Nurkolis
Orthodontic relapse, the return to a pre-treatment position after orthodontic correction, is driven by the RANKL/TNF-α-mediated ROS/Keap1/Nrf2 signaling axis. This mechanism triggers aseptic inflammation and oxidative stress, influencing bone resorption and formation. Antioxidants can mitigate oxidative stress, potentially improving post-orthodontic outcomes. This study explores the efficacy of antioxidant compounds derived from green seaweed/algae in managing orthodontic relapse. Green seaweed/algae extracts were prepared via sonication, and bioactive compounds were identified using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) analysis. Compounds underwent bioactivity prediction, toxicity assessment, and drug-likeness evaluation, revealing significant therapeutic potential. Network pharmacology and molecular docking identified key proteins associated with orthodontic relapse, including IL-1β, STAT3, ESR1, MAPK1, JAK2, and HMOX1. Molecular docking simulations indicated favorable binding energies for green seaweed compounds, particularly the alkaloids adenosine (ΔG −6.9 to −7.3 kcal/mol) and lycopodine (ΔG −6.3 to −8.5 kcal/mol), against targeted proteins, matching or outperforming standard drugs such as s-ibuprofen (ΔG −6.7 kcal/mol). In vitro assays confirmed the antioxidant activity of these compounds, with EC50 dose of 52.2–54.2 μg/mL for ABTS radical scavenging capacities. Protein expression analysis in tibial-femoral bone marrow cells further demonstrated the potential of green seaweed/algae compounds to suppress osteoclastogenesis by modulating the RANKL/TNF-α-mediated ROS/Keap1/Nrf2 pathway. This research highlights the promise of green seaweed-derived antioxidants in reducing oxidative stress and managing orthodontic relapse, providing a foundation for future therapeutic developments. © 2024 The Author(s)
Department of Orthodontics, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia; Department of Orthodontics, Faculty of Dental Medicine, Universitas Airlangga, East Java, Surabaya, 60132, Indonesia; Department of Dental Biomedical Sciences, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia; Faculty of Medicine, Brawijaya University, Malang, 65145, Indonesia; Medical Study Program, Faculty of Medicine, State Islamic University of Maulana Malik Ibrahim (UIN Maulana Malik Ibrahim), Malang, 65144, Indonesia; Faculty of Medicine and Health, Universitas Muhammadiyah Jakarta, Jakarta, 15419, Indonesia; Department of Biology, Faculty of Mathematics and Natural Sciences, Sam Ratulangi University, Manado, 95115, Indonesia; Division of Clinical Nutrition, Department of Nutrition, Faculty of Medicine, Hasanuddin University, Makassar, 90245, Indonesia; Department of Pathology, College of Korean Medicine, Kyung Hee University, Kyungheedae-Ro 26, Dong-Daemun-Gu, Seoul, 05254, South Korea; Department of Biotechnology, Faculty of Biotechnology, Atma Jaya Catholic University of Indonesia, Jakarta, 12930, Indonesia; Food Science Program, Department of Chemistry, Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, K1S 5B6, ON, Canada; Department of Biological Sciences, Faculty of Sciences and Technology, State Islamic University of Sunan Kalijaga (UIN Sunan Kalijaga), Yogyakarta, 55281, Indonesia
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