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<p>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease involving dysregulated matrix metalloproteinase-9 (MMP9) activity, leading to excessive extracellular matrix deposition and lung tissue deterioration. This study investigated bioactive compounds from <i>Mentha piperita</i> L. as potential MMP9 inhibitors for IPF therapy. Gas chromatography-mass spectrometry (GC–MS) analysis identified nine phytochemicals in the methanolic extract of peppermint leaves. Drug-likeness screening using Lipinski’s Rule of Five identified two lead compounds: (-)-carvone and cis-dihydrocarvone. ADMET analysis revealed favorable pharmacokinetic properties, including appropriate solubility (−3.089 and −3.12, respectively) and blood–brain barrier permeability values (0.345 and 0.357). TOPKAT toxicity prediction classified both compounds as non-carcinogenic with negligible skin sensitization potential. Molecular docking against MMP9 (PDB ID: 1GKD) yielded MolDock scores of −84.22 for (-)-carvone and  −87.47 for cis-dihydrocarvone, indicating strong binding affinity. Molecular dynamics simulations over 100&#xa0;ns demonstrated stable protein–ligand complexes with consistent RMSD values (~ 0.8&#xa0;Å for ligand), sustained hydrogen bonding interactions, and minimal conformational changes. Key residues LEU188, VAL398, HIS401, and TYR423 were identified as critical for binding stability. These computational findings establish (-)-carvone and cis-dihydrocarvone as promising MMP9 inhibitor candidates for IPF treatment, warranting in vitro and in vivo experimental validation.</p>

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Molecular dynamics simulation and structural characterization of (-)-carvone and cis-dihydrocarvone from Mentha piperita L. as potential MMP9 inhibitors for idiopathic pulmonary fibrosis therapy

  • 期刊论文

  • 发表日期：

    2025年12月8日

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  • G. Koteswara Reddy,
  • Yuvaraj Dinakarkumar,
  • Korukonda Satwik,
  • Allam Sai Sree Thanay,
  • Bobba Devi Sri Siddhartha,
  • Nandigum Sai Anvesh,
  • Selvaraj Arokiyaraj,
  • Panneerselvam Theivendren

摘要

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease involving dysregulated matrix metalloproteinase-9 (MMP9) activity, leading to excessive extracellular matrix deposition and lung tissue deterioration. This study investigated bioactive compounds from Mentha piperita L. as potential MMP9 inhibitors for IPF therapy. Gas chromatography-mass spectrometry (GC–MS) analysis identified nine phytochemicals in the methanolic extract of peppermint leaves. Drug-likeness screening using Lipinski’s Rule of Five identified two lead compounds: (-)-carvone and cis-dihydrocarvone. ADMET analysis revealed favorable pharmacokinetic properties, including appropriate solubility (−3.089 and −3.12, respectively) and blood–brain barrier permeability values (0.345 and 0.357). TOPKAT toxicity prediction classified both compounds as non-carcinogenic with negligible skin sensitization potential. Molecular docking against MMP9 (PDB ID: 1GKD) yielded MolDock scores of −84.22 for (-)-carvone and  −87.47 for cis-dihydrocarvone, indicating strong binding affinity. Molecular dynamics simulations over 100 ns demonstrated stable protein–ligand complexes with consistent RMSD values (~ 0.8 Å for ligand), sustained hydrogen bonding interactions, and minimal conformational changes. Key residues LEU188, VAL398, HIS401, and TYR423 were identified as critical for binding stability. These computational findings establish (-)-carvone and cis-dihydrocarvone as promising MMP9 inhibitor candidates for IPF treatment, warranting in vitro and in vivo experimental validation.