Quantitative Determination of Oxalic and Phytic Acids of Lippia Multiflora Moldenke (Verbenaceae) Leaves and In Silico Study of Their Interaction with Haemoglobin S and 2,3-DPG-Mutase

Abstract

The aim of this study is to measure oxalic and phytic acids from the leaves of Lippia multiflora and to evaluate their anti-sickle cell activity in silico. The histological characterization of the leaves of L. multiflora was performed by optical micrography. Theseanti-nutritional factors oxalic acid and phytic acid were determined by the standard method. Discovery Studio, ChemDraw and Autodock Vina software were used in molecular modeling. The pharmacokinetic and toxicological profile was evaluated using the bioinformatics descriptor SWISSADME. Histological analysis shows that fibres, sclerites and suber fragments are characteristic tissues of L. multiflora leaves. These leaves contain oxalic acid (insoluble oxalates: 51.457±27.653 mg/100 g DM; total oxalates: 59.483±0.704 mg/100 g MS; calcium oxalates: 0.216±0.0021 mg/100 g MS) and phytic acid (18.400±5.062 mg/100 g MS). Oxalic acid interacts more effectively with 2,3-diphospgoglycerate mutase (ΔG=-5.30±0.03 kcal/mol) while phytic acid interacts more strongly with deoxyhemoglobin S (ΔG=-9.30±0.01 kcal/mol) in silico. Phytic acid interacts with deoxyhemoglobin S by two hydrogen bonds (Arginine 31 and Lysine 120) while oxalic acid forms five hydrogen bonds with 2,3-DPG mutase (Arginine 10, Asparagine 17; Arginine 62; Histidine 188 and Glycine 189). The pharmacopharmacokinetic profile shows that these compounds do not inhibit cytochrome P450 complex enzymes and are not toxic. Both compounds represent added value for L. multiflora in the symptomatic treatment of sickle cell disease. In addition to attenuating hypersideremia, they can inhibit erythrocyte sickle formation via interaction with both protein receptors.