Molecular docking and pharmacokinetic profiling of bioactive compounds from Nigella sativa L. and Trigonella foenum-graecum for targeting TNF-α and IL-۶ in diabetic wounds

Introduction: Diabetic wounds represent a significant challenge in the clinical management of people with diabetes. Current pharmacological approaches for diabetic wound treatment have demonstrated adverse effects, necessitating the investigation of alternative therapeutic agents, including extracts from Nigella sativa L. and Trigonella foenum-graecum. This study aimed to evaluate the therapeutic potential of bioactive compounds from a combination of those two extracts as new inhibitors of tumor necrosis factor-alpha (TNF-α) and interleukin-۶ (IL-۶), targeting their role in treating diabetic wounds. Methods: This research employed in silico techniques, particularly pharmacokinetic analysis and molecular docking. The drug-like properties of bioactive compounds were analyzed using Swiss ADME. The ADMET predictions of bioactive compounds were analyzed using the pkCSM tool. Molecular docking analysis was performed using AutoDock Vina integrated in PyRx ۰.۸, and the binding between the active ingredients and ۲AZ۵ and ۱P۹M receptors was determined using BIOVIA Discovery Studio Visualizer. Results: The results of ADME analysis explained that test compounds did not violate Lipinski’s rule, were easily absorbed, and had good permeability. Furthermore, the results showed that all tested compounds had a safe LD۵۰, but long-term use toxicity should be checked. Molecular docking results showed that N. sativa L. and T. foenum-graecum bioactive compounds inhibited TNF-α and IL-۶. Conclusion: All tested compounds may provide a safer alternative to synthetic treatments, but the most prominent compound for inhibiting TNF-α and IL-۶ is yuccagenin. Further experimental studies are expected to validate its efficacy and safety in treating diabetic wounds.