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Plant Science Today (PST)

Research Articles

Vol. 13 No. 3 (2026)

Computational insights into the hypocholesterolemic activity of Humboldtia vahliana Wight phytoconstituents

DOI
https://doi.org/10.14719/pst.11224
Submitted
10 August 2025
Published
29-04-2026 — Updated on 02-07-2026
Versions

Abstract

PCSK9 (Proprotein convertase subtilisin/Kexin type 9) is a promising therapeutic target for the development of novel cholesterol-lowering drugs. In this study, we investigated the potential of Humboldtia vahliana Wight as a natural PCSK9 inhibitor through a combination of gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS) analysis and molecular docking techniques. Methanolic bark extract of H. vahliana were subjected to GC-MS/MS, which identified several bioactive constituents, including Phenyl methyl ester (16.19 %),                               13-docosenamide (11.64 %), hexadecanoic acid (9.20 %) and D-glycero-D-ido-heptose (7.13 %). The PCSK9 inhibitory potential of these compounds was evaluated through molecular docking studies. Results revealed that the major active compounds exhibited strong binding affinities toward PCSK9, forming up to 5–6 hydrogen bonds with the target protein. This binding suggests a potential inhibitory mechanism that could down regulate PCSK9 activity. According to the docking results, d-Glycero-d-ido-heptose (-5.1 Kcal/mol) and phenyl methyl ester/acetic acid (-6.0 Kcal/mol) are promising natural inhibitors of PCSK9 that may reduce cholesterol via modifying LDL receptor recycling. Phenyl methyl ester is a possible lead chemical for PCSK9 inhibition, according to cross docking study, which shows that it has a greater binding energy of 1.1 Kcal/mol than the small-molecule PCSK9 inhibitor (-4.9 Kcal/mol), suggesting a better fit in the receptor cavity. Overall, the findings support the therapeutic promise of H. vahliana as a natural source of PCSK9 inhibitors, potentially contributing to the reduction of lipid levels in the bloodstream and the development of novel hypocholesterolemic agents. The presence of several moderate-binding compounds together points to a polypharmacological effect of the extract from H. vahliana.

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