2. Academic Validation
  3. Determination of the Lethal Concentrations of Two Phenolic Acid Derivatives Originated From the Edible Red Marine Macroalga (Bangia fuscopurpurea) Using the In Vivo Zebrafish Eleutheroembryo Model and Their In Silico Structure-Toxicity Relationship Study

Determination of the Lethal Concentrations of Two Phenolic Acid Derivatives Originated From the Edible Red Marine Macroalga (Bangia fuscopurpurea) Using the In Vivo Zebrafish Eleutheroembryo Model and Their In Silico Structure-Toxicity Relationship Study

  • Food Sci Nutr. 2026 Jan 21;14(1):e71182. doi: 10.1002/fsn3.71182.
Shi-Ying Huang 1,  Guiling Li 1 2,  Yi-Jia Shih 3,  Chang-Wei Hsieh 4 5 6,  Yun-Sheng Lin 7,  Jingwen Liu 1,  Tao Sun 8 9,  Chien-Wei Feng 10 11
Affiliations

Affiliations

  • 1 College of Ocean Food and Biological Engineering Jimei University Xiamen China.
  • 2 Fujian Marine Functional Food Engineering Technology Research Center Xiamen China.
  • 3 Sustainable Ocean Governance Center National Sun Yat-Sen University Kaohsiung Taiwan.
  • 4 Department of Food Science and Biotechnology National Chung Hsing University Taichung Taiwan.
  • 5 Department of Food Science National Ilan University Yilan Taiwan.
  • 6 Department of Medical Research China Medical University Hospital Taichung Taiwan.
  • 7 Department of Food Science National Pingtung University of Science and Technology Pingtung Taiwan.
  • 8 Center for Precision Medicine Huaqiao University Xiamen China.
  • 9 School of Medicine and School of Biomedical Sciences Huaqiao University Xiamen China.
  • 10 Department of Obstetrics and Gynecology Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung Taiwan.
  • 11 Center for Cancer Research Kaohsiung Medical University Kaohsiung Taiwan.
PMID: 41583019 DOI: 10.1002/fsn3.71182
Abstract

A 2023 study identified two phenolic acid derivatives (HBP2-3) in the extract from the edible macroalga (Bangia fuscopurpurea), and we previously demonstrated the in vitro neuroprotective effects of HBP2-3. However, the appropriate starting experimental concentration range for HBP2-3 in Animals remained unclear, and it was uncertain which compound might carry a lower toxicity risk. This study assessed the in vivo lethal dose of HBP2-3 and analyzed their in silico toxicological profiles to support a structure-toxicity relationship (STR) analysis. We predicted their LD50 using the tools GUSAR and DL-AOT, and determined their lethal concentrations (LC) using the in vivo zebrafish eleutheroembryo model. We predicted their toxicological properties using the tools (ADMETlab 3.0, TISBE, and embryoTox). An in vitro model was further selected to assess their toxicity. In in silico models, HBP2-3 showed potential to treat 12 parkinsonian syndromes, and HBP2 exhibited a higher rat oral LD50 than HBP3. In the in vivo zebrafish eleutheroembryo model, HBP2 (0.1-200 μM) and HBP3 (0.1-10 μM) did not induce mortality, and median LC (LC50) of HBP3 was estimated to be 115.48 μM. Compared with HBP3, HBP2 exhibited the following in silico advantages: (a) lower probabilities of nephrotoxicity and neurotoxicity; and (b) a reduced risk of developmental toxicity. In in vitro human neuronal IMR-32 cells, HBP3 exhibited greater cytotoxicity, potentially associated with the downregulation of Bcl-2 and the activation of Caspase-3. These advantages of HBP2 may be associated with an increased degree of hydroxylation.

Keywords

in silico evaluation; in vivo lethal dose; phenolic acid derivatives; structure–toxicity relationship; zebrafish.

Figures
Products