Background and Objectives: PON1 is a multi-functional antioxidant protein that hydrolyzes a variety of endogenous and exogenous substrates in the human system. Growing evidence suggests that the Leu55Met and Gln192Arg substitutions alter PON1 activity and are linked with a variety of oxidative-stress-related diseases. Materials and Methods: We implemented structural modeling and molecular dynamics (MD) simulation along with essential dynamics of PON1 and molecular docking with their endogenous (n = 4) and exogenous (n = 6) substrates to gain insights into conformational changes and binding affinity in order to characterize the specific functional ramifications of PON1 variants. Results: The Leu55Met variation had a higher root mean square deviation (0.249 nm) than the wild type (0.216 nm) and Gln192Arg (0.202 nm), implying increased protein flexibility. Furthermore, the essential dynamics analysis confirms the structural change in PON1 with Leu55Met vs. Gln192Arg and wild type. Additionally, PON1 with Leu55Met causes local conformational alterations at the substrate binding site, leading to changes in binding affinity with their substrates. Conclusions: Our findings highlight the structural consequences of the variants, which would increase understanding of the role of PON1 in the pathogenesis of oxidative-stress-related diseases, as well as the management of endogenous and exogenous chemicals in the treatment of diseases.

This study aimed to investigate the impact of Borreria hispida extract on gene expression in NRK-52E cells under conditions of glucotoxicity. Gene expression analysis was conducted using RT-PCR following the exposure of cultured NRK-52E cells to glucotoxic conditions and varying concentrations of Borreria hispida extract. The results demonstrated a dose-dependent increase in SIRT1 gene expression and a concomitant decrease in HIF-1λ, ET-1, and VEGFR-2 gene expressions upon treatment with Borreria hispida extract. Additionally, molecular docking studies suggested the potential inhibition of Rho-kinase as a mechanistic explanation for these effects. Borreria hispida extract may confer renoprotective benefits against glucotoxicity-induced cellular damage. The potential therapeutic utility of Borreria hispida extracts in managing renal complications associated with conditions such as diabetes. Furthermore, our docking studies shed light on the potential molecular mechanisms underlying the observed effects, suggesting interactions between phytochemicals present in Borreria hispida extract and the JNK-1 protein. These interactions may contribute to the augmentation of SIRT1 activity, further bolstering the extract's therapeutic utility in DKD.

This study aimed to investigate the impact of Orthosiphon stamineus extract on gene expression in NRK-52E cells under conditions of glucotoxicity. Gene expression analysis using RT-PCR was conducted following exposure of cultured NRK-52E cells to glucotoxic conditions and various concentrations of Orthosiphon stamineus extract. The results revealed a dose-dependent decrease in HIF-1α, ET-1 and VEGFR-2 gene expression levels upon treatment with Orthosiphon stamineus extract. The diverse array of phytochemicals found within Orthosiphon demonstrates a significant impact on the biochemical pathways implicated in the pathogenesis of the disease. Additionally, molecular docking studies suggested the potential inhibition of Rho-kinase as a mechanistic explanation for this observed effect. These findings suggest that Orthosiphon stamineus extract may possess renoprotective properties against glucotoxicity-induced cellular damage. This study contributes to understanding potential therapeutic interventions for managing renal complications associated with conditions such as diabetes.