Abstract:
Introduction: Pulmonary hypertension (PH) is a progressive, life-threatening disease
characterized by vascular remodeling, constriction, and thrombosis, primarily driven
by excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs).
Hypoxia is a key trigger in PH pathogenesis. The Wnt/β-catenin signaling pathway,
critical for cell fate, migration, and organogenesis, plays a pivotal role in PH, with β-
catenin mediating transcriptional activation of target genes upon Wnt ligand
stimulation.
Targeting Wnt/β-catenin signaling represents a promising therapeutic strategy for PH.
This study examines its role in hypoxia-exposed PASMCs and evaluates the
therapeutic potential of gallic acid and β-sitosterol through in-silico and in-vitro
approaches.
Objective: To study the role of isolated biomolecules from Mucuna pruriens gallic
acid and β-sitosterol on Wnt/ β-catenin mRNA expression in the human pulmonary
artery smooth muscle cells exposed to hypoxia.
Method: The current study used a computational method based on the ligand-protein
interaction technique to determine the therapeutic potential of gallic acid and β-
sitosterol with the Wnt/ β catenin pathway. The same compounds are used to
investigate. The Invitro study explored the role of gallic acid and β-sitosterol in
hypoxia-exposed PASMC lines.
Result and Discussion: The current study identified different pharmacological
properties of gallic acid and β-sitosterol bioactive molecules to analyze the in silicoADME/T properties. All were within Lipinski’s rule acceptable range, and molecular
docking analysis showed that β-sitosterol has more interaction sites with Wnt5a.
The Invitro study revealed that when HPASMC is exposed to hypoxia, there is
downregulation of the Wnt5a gene and upregulation of the β-catenin gene. β-sitosterol
and gallic acid can be attributed to inhibiting the β-catenin pathway via the
downregulation of β-catenin gene expression.
Conclusion: The present study focused on in-silico phytochemical analysis and in
vitro investigations to evaluate the potential therapeutic role of isolated biomolecules
from Mucuna pruriens seed extract β-sitosterol and gallic acid in hypoxia-exposed
pulmonary artery smooth muscle cells (HPASMCs). These findings suggest that
Mucuna pruriens, or its bioactive molecule gallic acid and β-sitosterol, may exert
protective effects against hypoxia-induced vascular remodeling by targeting the
Wnt/β-catenin signaling pathway.
