Structure-based virtual screening of plant-derived natural compounds as potential PPARα agonists for the treatment of dyslipidemia

Original Research

Abstract

Background: Nowadays, metabolic disorders such as dyslipidemia have become serious health problems in the modern world. PPARs are regulators of numberous metabolic pathways, hence there has been a huge increase in the development and use of the PPARs agonists, especially PPARα agonists as main therapeutic of dyslipidemia.

Objectives: The study aimed to explore potential plant-derived natural compounds as PPARα agonist agent for drug discovery of dyslipidemia. Methods: Structure-based virtual screening through molecular docking was conducted for 142 bioactive compounds from 29 medicinal plants on the main binding site of PPARα (PDB ID: 5HYK). Binding affinities and binding interactions between the ligands and PPARα were investigated.

Results: Screening results showed that 34 compounds had strong binding affinities into the PPARα (binding affinities of less than -8.0 kcal.mol-1), including 20 flavonoid, 4 terpenoid and 10 alkaloid compounds. Flavonoid was found as the best group which fitted well in the binding site of the PPARα. Top compounds were identified, including formononetin from Thermopsis alterniflora (-10.2 kcal.mol-1), diosmetin from Musa spp. (-10.1 kcal.mol-1), luteolin from Elsholtzia ciliate (-9.9 kcal.mol-1); steviol from Stevia rebaudiana (-9.4 kcal.mol-1); and tuberocrooline from Stemona tuberosa (-10.5 kcal.mol-1), respectively. These compounds showed the potential agonistic activities due to forming the hydrogen bonds as well as hydrophobic interactions with four key residues of the receptor such as Ser280, Tyr314, His440 and Tyr464.

Conclusions: These potential natural compounds may provide useful information in the drug design and discovery for anti-dyslipidemia agents.

Graphical abstract

Phytochemical compounds of Morus alba as anti-aging agent towards in silico binding to matrix metalloproteinase proteins

Original Research

Abstract

Skin aging is a natural phenomenon which is related to progressive loss of skin structural integrity and physiological function and affects aesthetics which has been of highly interest. Inhibition of matrix metalloproteinases (MMPs) such as MMP-1, MMP-3, MMP-9 is one of the potential approaches for anti-aging treatment as these targets are involved in molecular pathology to skin aging process from sunlight. The aim of the study was to investigate the binding affinity of 9 phytochemical compounds extracted from Morus alba Moraceae into the MMP enzymes leading to potential anti-aging activity by using in silico approaches including molecular docking and molecular dynamics simulations. All the compounds showed binding abilities into the targets. In particular, mulberrofuran H obtained the best docking results on the three MMPs. Molecular dynamics simulations of the complex of  mulberrofuran H and MMP-9 showed that this complex was stable. Combination of molecular docking and molecular dynamics simulations results, there was an important hydrophobic interaction between mulberrofuran H and His401 at the active site of the MMP-9, which determined the MMP-9 inhibitory potential of mulberrofuran H. The ligand mulberrofuran H was also stabilized into the MMP-9 protein by hydrogen bonds with Pro421 with the high occupancy of 77.67%. These results demonstrated the good binding of mulberrofuran H on the protein MMP-9 which highlighted its anti-aging potency.

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