In vitro targeted screening and molecular docking of stilbene, quinones, and flavonoid on 3T3-L1 pre-adipocytes for anti-adipogenic actions

• Published in: Naunyn-Schmiedeberg's archives of pharmacology Vol. 393; no. 11; pp. 2093 - 2106
• Main Authors: Bedi, Onkar, Aggarwal, Savera, Trehanpati, Nirupma, Ramakrishna, Gayatri, Grewal, Ajmer Singh, Krishan, Pawan
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2020; Springer Nature B.V
• Subjects: 3T3-L1 Cells; Adipocytes; Adipocytes - drug effects; Adipocytes - enzymology; Adipogenesis - drug effects; Alcohol Oxidoreductases - antagonists & inhibitors; Alcohol Oxidoreductases - metabolism; Animals; Anthraquinones - chemistry; Anthraquinones - pharmacokinetics; Anthraquinones - pharmacology; Arbutin - chemistry; Arbutin - pharmacokinetics; Arbutin - pharmacology; Biomedical and Life Sciences; Biomedicine; Cell Proliferation - drug effects; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - pharmacology; Enzymes; Fatty Acid Synthases - antagonists & inhibitors; Fatty Acid Synthases - metabolism; Fatty acids; Fatty Acids - metabolism; Fatty-acid synthase; Flavonoids; Metabolic disorders; Mice; Molecular Docking Simulation; Molecular Structure; Neurosciences; Original Article; Pharmacology/Toxicology; Quercetin; Quercetin - chemistry; Quercetin - pharmacokinetics; Quercetin - pharmacology; Quinones; Stilbenes - chemistry; Stilbenes - pharmacokinetics; Stilbenes - pharmacology; Structure-Activity Relationship; Thioesterase; Pterostilbene (PTS); 3T3-L1 adipocytes; Arbutin (ARB); Purpurin (PUR); Quercetin (QR)
• ISSN: 0028-1298; 1432-1912
• DOI: 10.1007/s00210-020-01919-w

In metabolic disorders like obesity, NAFLD and T2DM, adipocytes are dysfunctional. Hence, pharmacological interventions have importance in preventing differentiation of adipocytes and stimulating lipid uptake. We, therefore, investigated the effects of arbutin (ARB), purpurin (PUR), quercetin (QR), and pterostilbene (PTS) on adipocyte differentiation and lipid uptake using 3T3-L1 adipocytes. Further, in silico docking studies were achieved to investigate interactions of ARB, PUR, QR, and PTS with beta-ketoacyl reductase (KR) and thioesterase (TE) domains of fatty acid synthase (FAS) enzyme. Mature 3T3-L1 adipocytes were used to investigate the anti-adipogenic effect of selected pharmacological agents by Oil Red O staining and in vitro fatty acid uptake analysis. Molecular docking studies were performed to predict the binding interactions of selected compounds with KR and TE domains of FAS enzyme. All these agents significantly decrease the adipocyte differentiation and showed the stimulatory effect on fatty acid uptake in 3T3-L1 adipocytes. However, PTS and PUR proved to be anti-adipogenic, whereas ARB and QR showed significant effect on fatty acid uptake, compared to others. Similarly, all the compounds displayed significant binding interactions with KR and TE domains of FAS enzyme, supporting the results of in vitro studies. Graphical abstract