Macrotyloma Uniflorum Extract Counteracts Oxidative Imbalance Induced in Vitro by Sodium Oxalate in the Rat Kidney: In Silico Prediction of Quercetin and Kaempferol Superiority among Fitocomponents

Abstract

Background: Polycrystalline aggregates formed in the urinary system leads to the production of reactive oxygen species (ROS), the development of oxidative stress, and renal injury. Aim: This study investigated the antioxidant activity of major bioactive components of Macrotyloma uniflorum (MU) such as Quercetin, Kaempferol and Sitosterol and its polyphenolic extract against the pro-oxidant effects triggered by sodium oxalate. Methods: We performed molecular docking and molecular dynamics simulations of major bioactive components with superoxide dismutase, catalase, glutathione reductase and glutathione-S-transferase, key enzymes of human antioxidant system. Thereafter, we performed in silico Absorption Distribution Metabolism Excretion-Toxicity (ADME-Tox) analysis to find drug-like molecules, absorption, distribution, metabolism and toxicity study. Then, by spectrophotometric analysis we determined the antioxidant potential of MU extract and of Quercetin, Kaempferol and Sitosterol against oxidative imbalance due to hyperoxaluria in the renal tissue of female Wistar rats002E. Results: Molecular dynamics simulations showed high binding interactions of Quercetin with superoxide dismutase (SOD) and glutathione-S-transferase (GST) enzymes. In silico ADME/Tox data analysis showed the polyphenolic components may interact with the antioxidants, thus complementing their antioxidant potency. In wet lab studies, the sodium oxalate treatment specifically induced a significant elevation of lipid peroxidation with a concurrent decrease in reduced glutathione content, superoxide dismutase and catalase activities in a dose-dependent manner in kidney tissue homogenates. The MU extract and the bioactive components Quercetin, Kaempferol and Sitosterol were able to counteract sodium oxalate-induced oxidative stress in a dose-dependent manner, with Quercetin resulting the most effective compound. Conclusions: Our in vitro results suggest MU as a possible source of bioactive components to counteract renal injury thus representing an add-on therapy approach in the hyperoxaluria-induced kidney stone formation.