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<p>Elevated systolic and diastolic blood pressure affect significant risk factor for wide range of disease such as cardiovascular, renal and cerebrovascular related diseases. The present study aims to explore the potential of <i>Peronema canescens Jack</i> bioactive compounds as alternative antihypertensive agents and elaborates their underlying molecular mechanisms. A total of 30 secondary metabolites were screened using selection criteria such as molecular weight &lt; 500, HBA &lt; 10, HBD &lt; 5, and drug likeness score &gt; 0.18. Furthermore, several integrated tools were employed to construct the protein–protein interaction network and identify core hypertension-related proteins targeted by <i>P. canescens</i>. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also performed to investigate their biological functions. To verify the binding affinity of selected compounds with the core proteins, molecular docking and molecular dynamics simulations were conducted. Finally, we assessed their pharmacokinetic and toxicity profiles. The result, 13 compounds met the screening criteria. These compounds were founds to targeted 492 hypertension-related proteins, which were involved in more than 1,000 biological processes (cyclooxygenase and G-protein-coupled adenosine receptor signalling pathways being the most enriched). KEGG pathway analysis identified 227 pathways, with several closely related to hypertension, including the renin–angiotensin system and aldosterone-regulated sodium reabsorption. A total of 34 overlapping proteins were identified as important targets, suggesting crucial roles in hypertension. The Protein Protein Interaction network revealed three core targets: SRC, EGFR, and STAT3. Molecular docking showed that three compounds—coprostanone, PRG, and betulinic acid exhibited the highest binding affinities with the three proteins, at −10.3&#xa0;kcal/mol, −10.3&#xa0;kcal/mol, and −7.0&#xa0;kcal/mol, respectively. Molecular dynamic simulation verify that the binding were in stable condition and generates good RMSF fluctuations. In another point of view, the pharmacokinetics dan toxicity prediction pose that most compounds showed good absorption, distribution, metabolism, excretion dan safety (ADMET) profiles as drug candidates. In summary, we conclude that <i>P. canescens</i> Jack. shows strong potential and could suggest as an antihypertensive candidate. The identified mechanisms and ADMET profiles provide foundation for future in vitro and in vivo validation.</p>

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Unravelling potential of Peronema canescens Jack on hypertension : an integrative study of network Pharmacology, molecular docking and dynamics

  • 期刊论文

  • 发表日期：

    2026年1月14日

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  • Ysrafil Ysrafil,
  • Francisca Diana Alexandra,
  • Elsa Trinovita,
  • Fatmaria Fatmaria,
  • Agnes Frethernety,
  • Dio Syahputra,
  • Remi Ayu Pratika,
  • Badra Sanditya Rattyananda,
  • Ratna Surya Alwi,
  • Zulfiayu Sapiun,
  • Sari Eka Pratiwi,
  • Harlyanti Muthma’innah Mashar,
  • Firzan Nainu

摘要

Elevated systolic and diastolic blood pressure affect significant risk factor for wide range of disease such as cardiovascular, renal and cerebrovascular related diseases. The present study aims to explore the potential of Peronema canescens Jack bioactive compounds as alternative antihypertensive agents and elaborates their underlying molecular mechanisms. A total of 30 secondary metabolites were screened using selection criteria such as molecular weight < 500, HBA < 10, HBD < 5, and drug likeness score > 0.18. Furthermore, several integrated tools were employed to construct the protein–protein interaction network and identify core hypertension-related proteins targeted by P. canescens. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also performed to investigate their biological functions. To verify the binding affinity of selected compounds with the core proteins, molecular docking and molecular dynamics simulations were conducted. Finally, we assessed their pharmacokinetic and toxicity profiles. The result, 13 compounds met the screening criteria. These compounds were founds to targeted 492 hypertension-related proteins, which were involved in more than 1,000 biological processes (cyclooxygenase and G-protein-coupled adenosine receptor signalling pathways being the most enriched). KEGG pathway analysis identified 227 pathways, with several closely related to hypertension, including the renin–angiotensin system and aldosterone-regulated sodium reabsorption. A total of 34 overlapping proteins were identified as important targets, suggesting crucial roles in hypertension. The Protein Protein Interaction network revealed three core targets: SRC, EGFR, and STAT3. Molecular docking showed that three compounds—coprostanone, PRG, and betulinic acid exhibited the highest binding affinities with the three proteins, at −10.3 kcal/mol, −10.3 kcal/mol, and −7.0 kcal/mol, respectively. Molecular dynamic simulation verify that the binding were in stable condition and generates good RMSF fluctuations. In another point of view, the pharmacokinetics dan toxicity prediction pose that most compounds showed good absorption, distribution, metabolism, excretion dan safety (ADMET) profiles as drug candidates. In summary, we conclude that P. canescens Jack. shows strong potential and could suggest as an antihypertensive candidate. The identified mechanisms and ADMET profiles provide foundation for future in vitro and in vivo validation.