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<p>Although several plant-derived products have exhibited considerable anti-inflammatory effects in preliminary experiments, more research is needed to understand their molecular mechanism of action. Thereby, the goal of the current study was to investigate the chemical composition of <i>Putranjiva roxburghii</i> leaf methanolic extract to elucidate its beneficial effects on inflammation, and predict the implicated mechanism of action. The inhibitory effects of <i>P. roxburghii</i> different fractions against nitric oxide (NO) levels were determined using the Griess assay. Later, the most powerful fraction was evaluated for its suppressive activity toward iNOS by western blotting. Gas chromatography-mass spectrometry (GC–MS) was employed to identify the chemical profiling of the most potent anti-inflammatory fraction. Lastly, a combined docking and molecular dynamics (MD) study was performed to verify the mechanism of anti-inflammation. Our findings showed that the <i>P. roxburghii</i> hexane fraction at the highest concentration (100&#xa0;µg/ml) inhibits NO, and iNOS with percentages of 70 ± 4.4, and 95.5 ± 0.8, respectively. The results of GC–MS proved the presence of twenty-two compounds in the hexane fraction; diisooctyl phthalate, butyl octyl phthalate, <i>n</i>-heneicosane, <i>n</i>-octadecane, and hentriacontane were the main components (13.36%, 9.49%, 7.78%, 5.79%, and 5.02%, respectively). Molecular docking analysis demonstrated that hentriacontane had the highest binding affinity for Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex (−11.52&#xa0;kcal/mol), and the inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ) (−11. 21&#xa0;kcal/mol). The selected compound was simulated against the TLR4/MD-2 receptor and IKKβ for 20&#xa0;ns and 18&#xa0;ns at 310&#xa0;K using molecular dynamics. The outcomes confirmed that the inflammation inhibition mechanism of hentriacontane was predicted to be mediated by blocking the TLR4/MD-2 complex and IKKβ, thereby disrupting their inflammatory function. Totally, <i>P. Roxburghii</i> is a natural source of promising potential chemical compounds with anti-inflammatory properties. It could be used in investigations to develop anti-inflammatory drugs, and as alternative safer, and cheaper therapeutic agents.</p>

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Laboratory Investigation of Chemical Constituents and Anti-inflammatory Activity of Putranjiva roxburghii Hexane Fraction Based on Combined Docking and Molecular Dynamics Simulation Study

  • 期刊论文

  • 发表日期：

    2025年3月27日

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  • Ahmed R. Hamed,
  • Ahmed A. El-Rashedy,
  • Heba K. Nabih,
  • Mona M. Abdelmohsen,
  • Heba D. Hassanein,
  • Khaled A. Abdelshafeek,
  • Wael M. Elsayed

摘要

Although several plant-derived products have exhibited considerable anti-inflammatory effects in preliminary experiments, more research is needed to understand their molecular mechanism of action. Thereby, the goal of the current study was to investigate the chemical composition of Putranjiva roxburghii leaf methanolic extract to elucidate its beneficial effects on inflammation, and predict the implicated mechanism of action. The inhibitory effects of P. roxburghii different fractions against nitric oxide (NO) levels were determined using the Griess assay. Later, the most powerful fraction was evaluated for its suppressive activity toward iNOS by western blotting. Gas chromatography-mass spectrometry (GC–MS) was employed to identify the chemical profiling of the most potent anti-inflammatory fraction. Lastly, a combined docking and molecular dynamics (MD) study was performed to verify the mechanism of anti-inflammation. Our findings showed that the P. roxburghii hexane fraction at the highest concentration (100 µg/ml) inhibits NO, and iNOS with percentages of 70 ± 4.4, and 95.5 ± 0.8, respectively. The results of GC–MS proved the presence of twenty-two compounds in the hexane fraction; diisooctyl phthalate, butyl octyl phthalate, n-heneicosane, n-octadecane, and hentriacontane were the main components (13.36%, 9.49%, 7.78%, 5.79%, and 5.02%, respectively). Molecular docking analysis demonstrated that hentriacontane had the highest binding affinity for Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex (−11.52 kcal/mol), and the inhibitor of nuclear factor kappa-B (NF-κB) kinase subunit beta (IKKβ) (−11. 21 kcal/mol). The selected compound was simulated against the TLR4/MD-2 receptor and IKKβ for 20 ns and 18 ns at 310 K using molecular dynamics. The outcomes confirmed that the inflammation inhibition mechanism of hentriacontane was predicted to be mediated by blocking the TLR4/MD-2 complex and IKKβ, thereby disrupting their inflammatory function. Totally, P. Roxburghii is a natural source of promising potential chemical compounds with anti-inflammatory properties. It could be used in investigations to develop anti-inflammatory drugs, and as alternative safer, and cheaper therapeutic agents.