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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
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Naturally Occurring PCSK9 Inhibitors.

Maria Pia Adorni1, Francesca Zimetti2, Maria Giovanna Lupo3

  • 1Department of Medicine and Surgery-Unit of Neurosciences, University of Parma, 43125 Parma, Italy.

Nutrients
|May 21, 2020
PubMed
Summary

Discovering natural compounds that inhibit Proprotein convertase subtilisin/kexin type 9 (PCSK9) may lead to new oral medications. These could help more patients achieve lower LDL cholesterol levels and reduce cardiovascular events.

Keywords:
HNF1αPCSK9SREBPberberinecholesterolnutraceuticals

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Area of Science:

  • Biochemistry
  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Inhibiting Proprotein convertase subtilisin/kexin type 9 (PCSK9) is proven to reduce cardiovascular events by lowering LDL cholesterol.
  • Current PCSK9 inhibitors are not oral or affordable, limiting their widespread clinical benefit.
  • Development of oral, small-molecule PCSK9 inhibitors is a key therapeutic goal.

Purpose of the Study:

  • To review natural compounds and extracts with demonstrated PCSK9 inhibitory effects.
  • To explore the potential of these natural inhibitors as a basis for novel oral therapeutics.
  • To summarize available pharmacodynamic and pharmacokinetic data for identified compounds.

Main Methods:

  • Literature review of studies investigating natural PCSK9 inhibitors.
  • Analysis of experimental and clinical data on PCSK9 inhibition by natural products.
  • Compilation of pharmacodynamic and pharmacokinetic profiles where available.

Main Results:

  • Several natural compounds and extracts exhibit PCSK9 inhibitory activity.
  • These natural agents offer a potential starting point for developing new oral PCSK9-lowering drugs.
  • The review details the efficacy and characteristics of various natural PCSK9 inhibitors.

Conclusions:

  • Natural compounds represent a promising avenue for developing affordable, oral PCSK9 inhibitors.
  • Such therapies could enhance statin efficacy and improve patient achievement of LDL cholesterol targets.
  • Further research into these natural products may yield significant advancements in cardiovascular disease management.