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<p><i>Pinus pinaster</i> Aiton, commonly known as <i>maritime pine</i>, is extensively utilized in traditional Mediterranean medicine for a variety of ailments, particularly renal dysfunctions. Its bark is notably high in polyphenols, which may possess therapeutic properties. This study aimed to assess the protective effects of a hydroalcoholic bark extract from <i>P. pinaster</i> (PPBE) against nephrocalcinosis induced by ethylene glycol (EG) in rats, supplemented by in silico toxicity and ADMET profiling. Nephrocalcinosis was induced by providing rats with EG in their drinking water for 30 days, during which they were administered daily doses of either PPBE or cystone. We analyzed urinary parameters (volume, pH, electrolytes), conducted serum biochemical assessments, and measured creatinine clearance. Renal histopathology was performed to evaluate tissue changes. In silico studies were carried out on the main phytoconstituents to predict their toxicity and pharmacokinetics. The EG-treated rats exhibited significant urinary and biochemical alterations, including decreased urine output, pH, and electrolyte excretion, coupled with elevated serum creatinine and urea levels. Notably, treatment with PPBE (200&#xa0;mg/kg) significantly boosted urine volume from 6 ± 1&#xa0;ml to 12 ± 1&#xa0;ml (<i>p</i> &lt; 0.001), enhanced creatinine clearance (0.44 ± 0.09&#xa0;ml/min), reduced urinary calcium and phosphate levels, and increased magnesium levels when compared to the EG group. Histopathological evaluations confirmed renal protection in the treated groups. In silico analyses revealed favorable ADMET properties and low toxicity predictions for key constituents, particularly catechin and proanthocyanidin. Overall, PPBE demonstrates protective effects against nephrocalcinosis by restoring urinary and biochemical equilibrium, inhibiting crystal formation, and safeguarding renal tissue. The integration of in vivo and in silico findings highlights its therapeutic potential and pinpoints promising bioactive candidates for future research.</p> Graphical abstract <p></p>

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Moroccan Pinus pinaster bark as a dual in vivo and in silico nephroprotective agent against nephrocalcinosis: toxicity and ADMET insights

  • 期刊论文

  • 发表日期：

    2026年1月16日

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  • Widad Tbatou,
  • Asmae Elghouizi,
  • Ghizlane Nouioura,
  • Meryem Bakour,
  • Marouane Aouji,
  • Naima Mammate,
  • Badiaa Lyoussi,
  • Zineb Benziane Ouaritini

摘要

Pinus pinaster Aiton, commonly known as maritime pine, is extensively utilized in traditional Mediterranean medicine for a variety of ailments, particularly renal dysfunctions. Its bark is notably high in polyphenols, which may possess therapeutic properties. This study aimed to assess the protective effects of a hydroalcoholic bark extract from P. pinaster (PPBE) against nephrocalcinosis induced by ethylene glycol (EG) in rats, supplemented by in silico toxicity and ADMET profiling. Nephrocalcinosis was induced by providing rats with EG in their drinking water for 30 days, during which they were administered daily doses of either PPBE or cystone. We analyzed urinary parameters (volume, pH, electrolytes), conducted serum biochemical assessments, and measured creatinine clearance. Renal histopathology was performed to evaluate tissue changes. In silico studies were carried out on the main phytoconstituents to predict their toxicity and pharmacokinetics. The EG-treated rats exhibited significant urinary and biochemical alterations, including decreased urine output, pH, and electrolyte excretion, coupled with elevated serum creatinine and urea levels. Notably, treatment with PPBE (200 mg/kg) significantly boosted urine volume from 6 ± 1 ml to 12 ± 1 ml (p < 0.001), enhanced creatinine clearance (0.44 ± 0.09 ml/min), reduced urinary calcium and phosphate levels, and increased magnesium levels when compared to the EG group. Histopathological evaluations confirmed renal protection in the treated groups. In silico analyses revealed favorable ADMET properties and low toxicity predictions for key constituents, particularly catechin and proanthocyanidin. Overall, PPBE demonstrates protective effects against nephrocalcinosis by restoring urinary and biochemical equilibrium, inhibiting crystal formation, and safeguarding renal tissue. The integration of in vivo and in silico findings highlights its therapeutic potential and pinpoints promising bioactive candidates for future research.

Graphical abstract