In vitro and in silico investigation of garlic’s (Allium sativum) bioactivity against ۱۵-lipoxygenase mediated inflammopathies

Introduction: Garlic (Allium sativum) is widely used as a flavor-enhancing dietary ingredient and exhibits a wide spectrum of pharmacological effects. This study aimed to investigate the therapeutic effects of aqueous garlic extract to explore the bioactivity against ۱۵-lipoxygenase (۱۵-LOX) mediated inflammopathies. Methods: In this study, the antioxidant (DPPH free radical scavenging assay and reducing power assay), anti-inflammatory (hypotonicity-induced hemolysis assay and ۱۵-LOX inhibition assay) and anticoagulation (serine protease inhibition assay and prothrombin time assay) effects of the aqueous garlic extract were investigated. Furthermore, in silico molecular docking and dynamic simulation analysis of reported small compounds of garlic against ۱۵-LOX۱ and ۱۵-LOX۲ were performed to figure out the most efficient phytochemical ligands and validate the anti-inflammatory potential. Results: The DPPH scavenging effect and the reducing power of the extract were found with the IC۵۰ of ۲۱۳.۸۷ ± ۱.۴۹ μgmL-۱ and EC۵۰ of ۱۲۴.۷۸ ± ۳.۳۹ μgmL-۱, respectively. In the hypotonicity-induced hemolysis and ۱۵-LOX inhibition assay, the IC۵۰ values were observed as ۱۴۷.۵۹ ± ۲.۹۸ μgmL-۱ and ۲۵۰.۰۵ ± ۸.۴۸ μgmL-۱, respectively. The extract inhibited serine protease activity with an IC۵۰ of ۳۰۱.۳۳ ± ۱.۳۱ μgmL-۱ and prevented blood coagulation for ۱۰.۰۵ ± ۰.۳۵ minutes in prothrombin time assay. The in silico study identified Rhamnetin as a potential ۱۵-LOX۱ and ۱۵-LOX۲ inhibitor, and it exhibited a stable interaction with the targets throughout the ۱۰۰ ns dynamic simulation. Conclusion: The findings of this study provide molecular insights into garlic’s medicinal properties as well as its bioactive compounds, which can be potential therapeutic interventions for ۱۵-LOX mediated inflammations.

Keywords:

Antioxidant , Anti-inflammatory agents Anticoagulant , Inflammation , Phenolic compounds