Stevia-Derived Diterpenoids as Potential Dopamine D2 Receptor Antagonists for Insomnia and Schizophrenia Therapy: An In Silico Study
DOI:
https://doi.org/10.31351/vol35iss2pp105-124Keywords:
water-stevia-extracts, diterpenoid compounds, D2-dopamin, anti-insomniaAbstract
Insomnia is the second most common mental disorder and causes several health risks. Stevia water extract is a popular natural sweetener and promotes health benefits including antioxidant, anti-inflammatory, antimicrobial, antidiabetic, anticancer, anti-hypertension. This study investigates the potential of Diterpenoid-Water-Extract Compounds as a target for insomnia therapy through the use of dopamine receptors (D2/D4) in silico. This research method includes: Stevia water extract compounds resulting from LCMS analysis as ligands and proteins of D4 dopamine receptor (id: 5wiv) and D2 dopamine receptor (id: 6cm4) were taken from the database, then native ligands and bioactive compounds were docked again and their interactions were analyzed. The best binding affinity results are based on the stability of the interaction using molecular dynamics simulations. The docking results showed that several water stevia extract compounds bound to the same dopamine D2 and D4 receptor sites as the original ligand. Binding affinity shows relatively similar scores for both water and original stevia extract compounds against the D2-Dopamine dopamine receptor. This results, molecular docking analysis of water stevia extract compounds shows that the active site interactions and binding affinity are the best for selective D2-Dopamine receptors, including Steviolmonoside, Steviolbioside, Sterebin-G, -E, -B, -M, -A, and -K , Steviol, and Isosteviol. These diterpenoid compounds also have stable interactions with D2-dopamine in dynamic molecular simulations. The conclusion of this research is the diterpenoids compounds in water stevia extracts, such as Steviolbioside, Steviolmonoside, Rebaudioside G, Sterebin G, Sterebin M, Steviol, and Isosteviol have the ability to target insomnia therapy through D2-Dopamine receptor inhibition/antagonist
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