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<p><i>Egletes viscosa</i> (L.) Less., Asteraceae (with the vernacular name of “macela”), is known for its gastroprotective properties in traditional medicine in Brazil. Herein, we evaluated the toxicity and antiresorptive activity of 12-acetoxyhawtriwaic acid lactone, a diterpene obtained from <i>E. viscosa</i>. 12-Acetoxyhawtriwaic acid lactone has been demonstrated to have biological effects which might be important during periodontitis, a bone disorder. Molecular docking studies analyzed ADME-Tox properties of 12-acetoxyhawtriwaic acid lactone and evaluated its binding performance against targets associated with bone loss. Periodontitis was induced by a ligature around the mandibular first molars. The mice received (gavage) 12-acetoxyhawtriwaic acid lactone (12.5, 25, 50&#xa0;mg/kg) for 14&#xa0;days. Bone loss was assessed through morphometric and histometric analysis. Picrosirius Red staining was performed in mandible sections. We investigated in gingival tissues by RT-qPCR RANK-L/OPG and catalase mRNA expression levels, and by colorimetric assay catalase and superoxide dismutase activities. The in vivo toxicity of 12-acetoxyhawtriwaic acid lactone was evaluated. In silico assays suggested good oral bioavailability and hepatotoxicity, and the interactions of 12-acetoxyhawtriwaic acid lactone with RANKL/OPG and catalase showed firm bonds. In in vivo experiments, 12-acetoxyhawtriwaic acid lactone reduced bone loss. Although 12-acetoxyhawtriwaic acid lactone (25 or 50&#xa0;mg/kg) produced liver and renal toxicity, it (12.5&#xa0;mg/kg) showed no signs of toxicity, increased collagen type I, reduced RANK-L mRNA levels and increased OPG and catalase mRNA levels, and enhanced catalase and superoxide dismutase activities. 12-Acetoxyhawtriwaic acid lactone (12.5&#xa0;mg/kg) was safe and had anti-resorptive effects during periodontitis in mice, showing antioxidant activity with the involvement of the RANK-L/OPG pathway. These findings point to a novel application for <i>E. viscosa</i> and highlights the need for cautious utilization of medicinal plants.</p> Graphical Abstract <p></p>

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Exploring the Toxicity and Antiresorptive Activity of a Diterpene from Egletes viscosa in Mice: In Silico and In Vivo Studies

  • 期刊论文

  • 发表日期：

    2025年2月3日

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  • Iara Laís L. de Sousa,
  • Iracema M. de Melo,
  • Jordânia M. de O. Freire,
  • Andreia S. Lima,
  • Antônia T. A. Pimenta,
  • Mary Anne S. Lima,
  • River Jordan O. Mesquita,
  • Joao Henrique S. Luciano,
  • José Jackson do N. Costa,
  • Paula Goes,
  • Renata F. de C. Leitão,
  • Vanessa C. de S. Ferreira,
  • Karuza Maria A. Pereira,
  • Helyson Lucas B. Braz,
  • Hellíada V. Chaves,
  • Mirna M. Bezerra

摘要

Egletes viscosa (L.) Less., Asteraceae (with the vernacular name of “macela”), is known for its gastroprotective properties in traditional medicine in Brazil. Herein, we evaluated the toxicity and antiresorptive activity of 12-acetoxyhawtriwaic acid lactone, a diterpene obtained from E. viscosa. 12-Acetoxyhawtriwaic acid lactone has been demonstrated to have biological effects which might be important during periodontitis, a bone disorder. Molecular docking studies analyzed ADME-Tox properties of 12-acetoxyhawtriwaic acid lactone and evaluated its binding performance against targets associated with bone loss. Periodontitis was induced by a ligature around the mandibular first molars. The mice received (gavage) 12-acetoxyhawtriwaic acid lactone (12.5, 25, 50 mg/kg) for 14 days. Bone loss was assessed through morphometric and histometric analysis. Picrosirius Red staining was performed in mandible sections. We investigated in gingival tissues by RT-qPCR RANK-L/OPG and catalase mRNA expression levels, and by colorimetric assay catalase and superoxide dismutase activities. The in vivo toxicity of 12-acetoxyhawtriwaic acid lactone was evaluated. In silico assays suggested good oral bioavailability and hepatotoxicity, and the interactions of 12-acetoxyhawtriwaic acid lactone with RANKL/OPG and catalase showed firm bonds. In in vivo experiments, 12-acetoxyhawtriwaic acid lactone reduced bone loss. Although 12-acetoxyhawtriwaic acid lactone (25 or 50 mg/kg) produced liver and renal toxicity, it (12.5 mg/kg) showed no signs of toxicity, increased collagen type I, reduced RANK-L mRNA levels and increased OPG and catalase mRNA levels, and enhanced catalase and superoxide dismutase activities. 12-Acetoxyhawtriwaic acid lactone (12.5 mg/kg) was safe and had anti-resorptive effects during periodontitis in mice, showing antioxidant activity with the involvement of the RANK-L/OPG pathway. These findings point to a novel application for E. viscosa and highlights the need for cautious utilization of medicinal plants.

Graphical Abstract