In silico approach to study the metabolism and biological activities of oligomeric proanthocyanidin complexes

Abstract

OBJECTIVES:Over the past three decades, numerous studies have focused on the biological activities of oligomeric proanthocyanidins (OPCs) in the prevention of many diseases such as neurodegeneration, atherosclerosis, tumorigenesis, and microbial infections. OPC has redox-active metabolites which could modulate the intracellular redox equilibrium to maintain the antioxidant homeostasis. This redox-modulating efficiency of OPC could provide new insights into therapeutic approaches that could reduce the burden of cardiovascular diseases. The main objective of this study was to explore the biological and metabolic activities of OPC using in silico approaches.METHODS:To validate the above objective, chemoinformatic tools were used to predict the metabolism of OPC after ingestion, based on both the ligand and structure of the constituent compounds.RESULTS:OPC showed possible sites for Phase I metabolism by cytochrome P450, and the metabolites obtained thereafter may be responsible for its biological activities. Absorption, distribution, metabolism, elimination, and toxicity properties showed efficient absorption, distribution, and metabolism of OPC, without toxicity.CONCLUSION:Thus, from the results obtained, OPC could be strongly recommended as a cardioprotective drug.

A Practical Strategy for Exploring the Pharmacological Mechanism of Luteolin Against COVID-19/Asthma Comorbidity: Findings of System Pharmacology and Bioinformatics Analysis

“…The criteria of the Lipinski's rule of five are as follows: logP ≤5, MW ≤500 Da, n-ON ≤10, and n-OHNH ≤5 (38). In addition, the topological polar surface area (TPSA) value is a key indicator for evaluating and predicting the oral bioavailability of molecular compounds, and the TPSA value of ≤140 Å represents good oral bioavailability (37,(62)(63)(64). %ABS value calculated according to TPSA value between 67% and 83% means an ideal oral bioavailability (37,(62)(63)(64).…”

“…In addition, the topological polar surface area (TPSA) value is a key indicator for evaluating and predicting the oral bioavailability of molecular compounds, and the TPSA value of ≤140 Å represents good oral bioavailability (37,(62)(63)(64). %ABS value calculated according to TPSA value between 67% and 83% means an ideal oral bioavailability (37,(62)(63)(64). Surprisingly, the results showed that luteolin met the criteria of logP = 1.97 < 5, MW = 286.24 < 500 Da, n-ON = 6 < 10, and n-OHNH = 4 <5, and the value of TPSA at 111.12 Å < 140 and %ABS at 70.66 that ranged from 57.95% to 78.98% were at the range of ideal oral bioavailability as shown in Table 1.…”

“…Eight open-source databases were used to obtain the targets related to luteolin, namely, TCMSP (54), PharmMapper (354), Swiss Target Prediction (100), STITCH (10), CTD (194), DGIdb (32), ECTM (72), and SymMap (64). We established a luteolin-related target set by syndicating a union of the predicted results and 638 targets related to luteolin were gathered after the removal of duplications and transferring gene symbols (Figure 2A).…”

“…It is well accepted that a compound that complies with the Lipinski's rule of five tends to have favorable pharmacokinetic properties and further improves the possibility of evolving into a drug candidate (65,66). TPSA comprises intestinal absorption, bioavailability, permeabilization of Caco-2, and blood-brain barrier penetration, and TPSA value of oral drugs should not exceed 140 Å (37,(62)(63)(64). It is considered that a compound with physicochemical properties of TPSA value of ≤140 Å and n-rotb ≤10 has a bigger potential to show good oral bioavailability (37).…”

“…A molecular compound with a bioactivity value of >0.00 has a great possibility to exert great biological activity, while a bioactivity score between −0.50 and 0.00 is considered to moderately perform biological activity and bioactivity value of ≤0.50 is perceived as poor biological activity (37,39,63,64). The results of bioactivity analysis showed that the pharmacological effects of luteolin theoretically involve several mechanisms, including excellent interactions with kinase inhibitor, nuclear receptor ligand, and enzyme inhibitor and moderate interactions with GPCR ligands, ion channel modulator, and protease inhibitor.…”