Shinta Kusumawati, Agustina T. Endharti, Farhad Balafif, Shahdevi N. Kurniawan, Rabjhany Anaqah, Husnul Khotimah
Parkinson's disease is a neurodegenerative disease characterized by degeneration of dopaminergic neurons. There is no drug can inhibit its progression. The dopamine receptor D2 (DRD2) subtype is pivotal in Parkinson's disease for decreasing locomotor activity. Thymoquinone is an active component of N. sativa that prevents dopamine degradation. Madecassoside is a major chemical component of C.asiatica that contributes to anti-apoptosis in Parkinson's disease. There is currently no research on the two chemicals working together as an anti-Parkinsonian. This study investigated the potential of thymoquinone and madecassoside in regulating the dopamine DRD2 through an in silico approach. The PubChem database was used to retrieve SMILES for each bioactive chemical. The 3D structure of the target protein was obtained from the RSCB PDB database, while that of the PDB ligand control rotigotine (CID: 59227) and the wet-lab control pramipexole (CID: 119570) were obtained from the PubChem database. Molecular dynamics simulations were conducted with Biosciences. The results showed the compounds had a high binding affinity potential, particularly when compared to the wet-lab control, pramipexole. The overlay visualization findings were consistent with the results of H-bond, SASA, and RMSD, indicating that the control drug ligand rotigotine and thymoquinone could better preserve the conformational stability of the DRD2 protein than other ligands. Thymoquinone, a bioactive chemical, acted as the most similar activator to rotigotine. The madecassoside formed the greatest protein-ligand hydrogen bonds. Thymoquinone showed promise as a DRD2 modulator with neuroprotective potential, while madecassoside requires optimization. Findings support natural compounds for Parkinson’s disease via DRD2 modulation. © 2025 the authors. This work is licensed under the Creative Commons Attribution 4.0 International License.
Departmen of Medicine, Doctoral Program in Medical Science, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Department of Neurology, Faculty of Medicine, Universitas Islam Malang, Malang, 65144, Indonesia; Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Department of Neurosurgery, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Department of Medicine, Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia; Departement of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Malang, 65145, Indonesia
