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<p>Microbial biofilm, quorum sensing (QS)-mediated virulence and oxidative stress-induced inflammation are interrelated pathological processes that play a crucial role in persistent infections and chronic illnesses. Due to the multifactorially of such processes, isolated target-based approaches to therapy usually do not provide long-term effectiveness. A combined network pharmacology and multi-level computational approach was used in order to clarify the molecular mechanisms underlying the antibiofilm, anti-quorum sensing (anti-QS), and antioxidant activities of thirty-three bioactive compounds found in the essential oils (EOs) of <i>Citrus medica</i> cv. Liscia and cv. Rugosa. Human potential protein targets were predicted and intersected with disease-associated genes, and 317 common targets were obtained, which were further viewed in terms of protein-protein interaction network and hub gene. The analysis of the functional enrichment demonstrated that the targets play a large role in oxidative stress response, homeostasis of inflammatory response, signal transduction, apoptosis, and membrane-related processes. Molecular docking analysis reveals strong and consistent binding affinities of aromadendrene, germacrene D, caryophyllene oxide, and carvacrol to major hub proteins such as HSP90AA1, AKT1, TNF, IL6, IL1B, and STAT3. Principal component and secondary structure analysis, and molecular dynamics simulations were used to further assess the HSP90AA1–aromadendrene complex, which was found to be among the most stable complexes. Analysis based on density functional theory was used to support good electronic properties and chemical stability of the lead compound and ADMET profiling revealed acceptable pharmacokinetics and drug-like properties. All these findings indicate a multi-target, multi-pathway therapeutic paradigm and constitute a powerful computational framework of <i>Citrus</i>-based agents against biofilm-associated infections and oxidative stress-related disorders.</p>

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Therapeutic potential of Citrus medica L. (cv. ‘Liscia’ and cv. ‘Rugosa’) phytocompounds targeting biofilm formation, quorum sensing, and antioxidant defense mechanisms

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年7月7日

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  • Emira Noumi,
  • Khulood Fahad Alabbosh,
  • Qusai Alsenani,
  • Najah Alshammari,
  • Mamdouh Alshammari,
  • Mohd Adnan,
  • Ozgur Ceylan,
  • Adel Kadri,
  • Mejdi Snoussi,
  • Vincenzo De Feo

摘要

Microbial biofilm, quorum sensing (QS)-mediated virulence and oxidative stress-induced inflammation are interrelated pathological processes that play a crucial role in persistent infections and chronic illnesses. Due to the multifactorially of such processes, isolated target-based approaches to therapy usually do not provide long-term effectiveness. A combined network pharmacology and multi-level computational approach was used in order to clarify the molecular mechanisms underlying the antibiofilm, anti-quorum sensing (anti-QS), and antioxidant activities of thirty-three bioactive compounds found in the essential oils (EOs) of Citrus medica cv. Liscia and cv. Rugosa. Human potential protein targets were predicted and intersected with disease-associated genes, and 317 common targets were obtained, which were further viewed in terms of protein-protein interaction network and hub gene. The analysis of the functional enrichment demonstrated that the targets play a large role in oxidative stress response, homeostasis of inflammatory response, signal transduction, apoptosis, and membrane-related processes. Molecular docking analysis reveals strong and consistent binding affinities of aromadendrene, germacrene D, caryophyllene oxide, and carvacrol to major hub proteins such as HSP90AA1, AKT1, TNF, IL6, IL1B, and STAT3. Principal component and secondary structure analysis, and molecular dynamics simulations were used to further assess the HSP90AA1–aromadendrene complex, which was found to be among the most stable complexes. Analysis based on density functional theory was used to support good electronic properties and chemical stability of the lead compound and ADMET profiling revealed acceptable pharmacokinetics and drug-like properties. All these findings indicate a multi-target, multi-pathway therapeutic paradigm and constitute a powerful computational framework of Citrus-based agents against biofilm-associated infections and oxidative stress-related disorders.