Novel Drug Molecules for Atherosclerosis from Ginkgo biloba, an Endangered Himalayan Herb, Via Pharmacoinformatics
Shiwani Chahal1, Abhijit Debnath2, Pooja Ridhal1
1Department of Biotechnology, Chaudhary Devi Lal University, Sirsa-125055 (Haryana), India.
Insights
Ginkgo biloba compounds show potential for treating atherosclerosis by targeting multiple pathways. Isoginkgetin demonstrates significant therapeutic promise for mitigating cardiovascular disease progression.
Area of Science:
- Pharmacology
- Computational Chemistry
- Network Pharmacology
Background:
- Atherosclerosis, a chronic inflammatory disease, is a leading cause of global mortality, driven by lipid metabolism and vascular dysfunction.
- Cardiovascular diseases (CVDs) necessitate novel therapeutic strategies targeting key molecular pathways.
Purpose of the Study:
- To investigate the anti-atherosclerosis potential of bioactive compounds from Ginkgo biloba L.
- To evaluate compounds targeting Dipeptidyl Peptidase IV (DPP-IV), Endothelin B Receptor (ETB), and Peroxisome Proliferator-Activated Receptor alpha (PPAR-α).
Main Methods:
- In silico screening using Swiss ADME and Protox-II for safety and applicability.
- Molecular docking with AutoDock Vina and analysis using Discovery Studio Biovia.
- Molecular dynamics (MD) simulations and network pharmacology analysis (PPI, GO, KEGG enrichment).
Main Results:
- Eight Ginkgo biloba compounds were shortlisted; Isoginkgetin and Kaempferol showed significant binding affinities.
- Isoginkgetin demonstrated strong binding to DPP-IV and ETB receptors, outperforming Evogliptin and Bosentan.
- MD simulations confirmed the stability of the Isoginkgetin-ETB complex; network pharmacology identified Isoginkgetin's modulation of key CVD-related proteins.
Conclusions:
- Isoginkgetin exhibits multi-target therapeutic potential for atherosclerosis.
- This study highlights Isoginkgetin as a promising candidate for mitigating atherosclerosis initiation and progression.
Introduction:
Atherosclerosis, a chronic inflammatory disease driven by lipid metabolism dysregulation and vascular dysfunction, is a major contributor to cardiovascular diseases (CVDs), which is the leading cause of global mortality. The present study was undertaken to explore the anti-atherosclerosis potential (targeting DPP-IV, ETB, and PPAR-α) of bioactive compounds from Ginkgo biloba L.; the corresponding commercially available drugs, viz. Evogliptin, Bosentan, and Bezafibrate were taken as controls.
Methods:
Swiss ADME and Protox-II were utilized to evaluate the safety and applicability of G. biloba compounds. MGL Tools and AutoDock Vina were used for molecular docking, followed by analysis with Discovery Studio Biovia. MD simulation was performed for chosen complexes, and the resulting compound was examined for PPI, GO, and KEGG network enrichment using the Shiny GO server.
Results:
Eight compounds were shortlisted by using SwissADME and Protox-II servers, followed by molecular docking studies with AutoDock Vina. Six compounds exhibited stronger binding affinities against DPP-IV compared to Evogliptin (-7.1 kcal/mol), five outperforming Bosentan (- 7.5 kcal/mol) against ETB, and six better than Bezafibrate (-7.5 kcal/mol) against PPAR-α. Postdocking analysis identified Isoginkgetin for both DPP-IV and ETB receptors, while Kaempferol for PPAR-α. MD simulation studies of Isoginkgetin-DPP-IV, Isoginkgetin-ETB, and Kaempferol- PPAR-α resulted in the ETB-Isoginkgetin complex with the most favourable binding stability, rapid equilibration, and consistent hydrogen bonding. Network pharmacology analysis further highlighted Isoginkgetin's ability to modulate key proteins (CYP19A1, ESR2, GSK3B, XDH, PTGS2) associated with crucial CVD-related pathways.
Conclusion:
The findings highlight the multi-target therapeutic potential of Isoginkgetin in mitigating the initiation and progression of atherosclerosis.
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