Computational Study of Asian Propolis Compounds as Potential Anti-Type 2 Diabetes Mellitus Agents by Using Inverse Virtual Screening with the DIA-DB Web Server, Tanimoto Similarity Analysis, and Molecular Dynamic Simulation

Abstract

Propolis contains a wide range of pharmacological activities because of their various bioactive compounds. The beneficial effect of propolis is interesting for treating type-2 diabetes mellitus (T2DM) owing to dysregulation of multiple metabolic processes. In this study, 275 of 658 Asian propolis compounds were evaluated as potential anti-T2DM agents using the DIA-DB web server towards 18 known anti-diabetes protein targets. More than 20% of all compounds could bind to more than five diabetes targets with high binding affinity (<−9.0 kcal/mol). Filtering with physicochemical and pharmacokinetic properties, including ADMET parameters, 12 compounds were identified as potential anti-T2DM with favorable ADMET properties. Six of those compounds, (2R)-7,4′-dihydroxy-5-methoxy-8-methylflavone; (RR)-(+)-3′-senecioylkhellactone; 2′,4′,6′-trihydroxy chalcone; alpinetin; pinobanksin-3-O-butyrate; and pinocembrin-5-methyl ether were first reported as anti-T2DM agents. We identified the significant T2DM targets of Asian propolis, namely retinol-binding protein-4 (RBP4) and aldose reductase (AKR1B1) that have important roles in insulin sensitivity and diabetes complication, respectively. Molecular dynamic simulations showed stable interaction of selected propolis compounds in the active site of RBP4 and AKR1B1. These findings suggest that Asian propolis compound may be effective for treatment of T2DM by targeting RBP4 and AKR1B1.

Revealing Propolis Potential Activity on Inhibiting Estrogen Receptor and Heat Shock Protein 90 Overexpressed in Breast Cancer by Bioinformatics Approaches

“… 29 We found that neobavaisoflavone, methylophiopogonone A, 3’-methoxydaidzin, and genistin as novel candidates for anti-SARS CoV-2 infection through inhibition of S2 and Mpro, 48 whereas (RR)-(+)-30-senecioylkhellactone and pinobanksin-3-O-butyrate as novel aldose reductase inhibitors in the treatment of type-2 diabetes mellitus. 31 Moreover, diosmetin, cosmosiin, genistin, and 3’-methoxy-5’-hydroxyisoflavone-7-O-β-D revealed as novel candidates for inhibition of Streptococcus mutans activity in caries. 29 We also found that isoetin poses strong binding interaction to AChE, Caspase3, MAPK14, NF-kB, and TNF-α that related to neuroinflammation.…”

Bioinformatics searching of diagnostic markers and immune infiltration in polycystic ovary syndrome

“…NSC-94258, as an antineoplastic agent, its protein targets are AKR1B1 , CYP19A1 , HSD17B1 . Aldo-ketoreductase family 1, member B1 (AKR1B1), can prevent complications of diabetes and improve insulin sensitivity by catalyzing the reduction of glucose to sorbitol ( Zhan et al, 2019 ; Syaifie et al, 2022 ). In GCs, androstenedione and testosterone act as substrates and are converted by CYP19A1 to estrogen, the mutation of CYP19A1 may lead to the occurrence and the development of hyperandrogenemia in PCOS ( Kumariya et al, 2021 ).…”

New insights of propolis nanoformulation and its therapeutic potential in human diseases

“…Our previous studies also identified numerous flavonoid and phenolic acid compounds in propolis extract [ 71-73 ]. We have also explored 658 Asian propolis compounds that are majorly in the group of flavonoids, phenolic acid, and terpenoids [ 74 ]. The chemical structures of flavonoids and phenols group are presented in Figure 1 .…”