In-Silico Screening of HMG-CoA Reductase Inhibition Potential from Anredera cordifolia (Ten.) Steenis and Elephantopus scaber Linn.

Abstract

Background. Hypercholesterolemia is one of the most important risk factors in causing coronary heart disease. Hypercholesterolemia occurs because cholesterol synthesis in the body increases. The key enzyme of the cholesterol synthesis is hydroxymethylglutaryl-CoA (HMG-CoA) reductase. Drugs that inhibit HMG-CoA reductase activity such as statins are effective in inhibiting cholesterol synthesis. The problem arises because these drugs have many side effects. The use of natural ingredients as traditional medicine has been practiced by communities for generations. This has led to massive exploration and scientific studies on the biological activities of these medicinal plants.

Objective. Using an in-silico method, this study aimed to explore the pharmacokinetic and toxicity predictions, as well as the HMG-CoA reductase inhibitor activity of “Binahong” (Anredera cordifolia [Ten.] Steenis.) and elephant’s foot (Elephantopus scaber Linn.).

Methods. To collect samples, the Kanaya Knapsack database, USDA Dr Duke Phytochemical, PubChem, and Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) were used. To predict the activity of the active compounds, Pass Online software was used. To complete the drug-likeness analysis, the Lipinski rule of five and the Swiss Absorption, Distribution, Metabolism and Excretion (ADME) were employed. Protox II was used to predict the toxicity of the active compounds. Next, with PyRx v.0.9.8 software, molecular docking is utilized to do molecular screening. BioVia Discovery Studio 2019 was employed for data visualization.

Results. A number of the bioactive compounds of Anredera cordifolia and Elephantopus scaber had pa values >0.3 which indicate predicted activity as antihypercholesterolemic. The results of the pharmacokinetic analysis showed similar properties to drugs, allowing them to be absorbed well in the intestines and have no penetration into the blood-brain barrier. Toxicity prediction of the bioactive compounds was in the non-toxic category, although caution is required. The molecular docking results showed that three active compounds from Anredera cordifolia namely Ursolic acid, Calenduloside E, and Larreagenin A had a more negative binding energy compared to atorvastatin. Likewise, the active compounds from the Elephantopus scaber that had more negative binding energy than atorvastatin are Epifriedelanol, Stigmasterol glucoside, and Lupeol. However, the bioactive compounds of Larreagenin A and Lupeol do not have amino acid residues similar to the control on the active site of binding to the HMG-CoA reductase.

Conclusion. Both Anredera cordifolia and Elephantopus scaber plants showed potential as antihypercholesterolemic drugs through inhibition of HMG-CoA reductase activity, showed drug-likeness, and were able to be absorbed well in the intestines and had no penetration into the blood-brain barrier. Further studies are needed both in vitro and in vivo to examine the therapeutic effects of these two plants.