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<p>The aim of this work was to determine the vasodilator mechanism of action of the hexane extract of <i>Malvaviscus arboreus</i> Dill. ex Cav., Malvaceae, using an isolated organ model, quantitative structure–activity relationship (QSAR) analysis, and molecular docking tools. The vasodilator effect on rat aortic of hexane extract of <i>M. arboreus</i> (E<sub>max</sub> 53.4 ± 3.82%, EC<sub>50</sub> 57.82&#xa0;μg/ml) was significantly decreased (<i>p</i> ≤ 0.05) in the presence of <span>l</span>-NAME (10&#xa0;µM) and methylene blue (10&#xa0;µM), but not by atropine or indomethacin. A QSAR model employing four descriptors was developed: partition coefficient according to Crippen’s classification; molar refractivity according to Crippen’s classification; sum of atomic polarizabilities; and violations of Lipinski’s rules. The QSAR statistical parameters (R<sup>2</sup>, R<sup>2</sup>adj, MAE, RSS, and Fisher’s test) for the training and test groups are consistent with the internal validation coefficient (Qloo2 = 0.75), suggesting that the study can predict vasodilator activity. The QSAR model results indicate that the fatty acids of hexane extract of <i>M. arboreus</i> are 5<i>Z</i>,8<i>Z</i>,11<i>Z</i>,14<i>Z</i>)-octadecatetraenoic acid, (9<i>Z</i>,12<i>Z</i>,15<i>E</i>)-octadecatrienoic acid, (12<i>R</i>)-HETrE, and (7<i>Z,</i>11<i>Z</i>,14<i>E</i>)-eicosatrienoic acid play a significant role in vasodilator activity. The molecular docking study calculated a negative ∆Gb value and acceptable <i>Ki</i> affinities versus the control (the H4B cofactor) between the fatty acids of <i>M. arboreus</i> and endothelial nitric oxide synthase (eNOS). This study revealed that the hexane extract of <i>M. arboreus</i> exerts its vasorelaxant effect primarily through the nitric oxide and the cyclic guanosine monophosphate (NO-cGMP) pathway. According to the QSAR study and docking analysis, the fatty acids are the specialized metabolites of <i>M. arboreus</i> with high vasodilator predictive capacity and eNOS activation.</p> Graphical Abstract <p></p>

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Vasodilator Effect Through the Signaling Pathway NO-cGMP of Specialized Metabolites into Malvaviscus arboreus: Ex Vivo, QSAR, and Molecular Docking

  • 期刊论文

  • 发表日期：

    2025年8月28日

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  • Estephania López-Oliva,
  • Arabelly Jiménez-Rodríguez,
  • Tamara Juárez-Velázquez,
  • Cuauhtémoc Alvarado-Sánchez,
  • Rolffy Ortiz-Andrade,
  • Omar Aristeo Peña-Morán,
  • Litzia Ceron-Romero,
  • Oswaldo Hernández-Abreu

摘要

The aim of this work was to determine the vasodilator mechanism of action of the hexane extract of Malvaviscus arboreus Dill. ex Cav., Malvaceae, using an isolated organ model, quantitative structure–activity relationship (QSAR) analysis, and molecular docking tools. The vasodilator effect on rat aortic of hexane extract of M. arboreus (Emax 53.4 ± 3.82%, EC50 57.82 μg/ml) was significantly decreased (p ≤ 0.05) in the presence of l-NAME (10 µM) and methylene blue (10 µM), but not by atropine or indomethacin. A QSAR model employing four descriptors was developed: partition coefficient according to Crippen’s classification; molar refractivity according to Crippen’s classification; sum of atomic polarizabilities; and violations of Lipinski’s rules. The QSAR statistical parameters (R2, R2adj, MAE, RSS, and Fisher’s test) for the training and test groups are consistent with the internal validation coefficient (Qloo2 = 0.75), suggesting that the study can predict vasodilator activity. The QSAR model results indicate that the fatty acids of hexane extract of M. arboreus are 5Z,8Z,11Z,14Z)-octadecatetraenoic acid, (9Z,12Z,15E)-octadecatrienoic acid, (12R)-HETrE, and (7Z,11Z,14E)-eicosatrienoic acid play a significant role in vasodilator activity. The molecular docking study calculated a negative ∆Gb value and acceptable Ki affinities versus the control (the H4B cofactor) between the fatty acids of M. arboreus and endothelial nitric oxide synthase (eNOS). This study revealed that the hexane extract of M. arboreus exerts its vasorelaxant effect primarily through the nitric oxide and the cyclic guanosine monophosphate (NO-cGMP) pathway. According to the QSAR study and docking analysis, the fatty acids are the specialized metabolites of M. arboreus with high vasodilator predictive capacity and eNOS activation.

Graphical Abstract