Docking Studies and Molecular Dynamics Simulation of Compounds Contained in Kaempferia Galanga L. to Lipoxygenase (LOX) for Anti-Inflammatory Drugs

Inflammation is a self-protective response to start the healing process. An anti-inflammatory target worth developing are lipoxygenase inhibitors, which have been studied for several diseases, including severe respiratory disease. This research had the goals of estimating the activity of 21 compounds from K. galanga to inhibit the lipoxygenase (LOX) and estimating the bond stability of the ligand-LOX complex. Based on the compound’s affinity for LOX, the compounds in K. galanga were selected by utilizing the PLANTS docking software, with zileuton as the reference ligand. The GROMACS application was used to simulate the molecular dynamics of the LOX-ligand complex at 310 K. Based on the chemPLP score, most of the 21 K. galanga compounds showed a higher affinity towards 5-LOX compared to zileuton. δ-3-carene had the best affinity for 5-LOX. In the simulation of molecular dynamics until 20 ns, the RMSD of δ-3-carene and 5-LOX was not more than 0.03 nm or 0.3 Å, indicating that the whole system showed decent stability and had ‑1.67392 x 106 kcal/mol as the average potential energy. The results showed that K. galanga contains active components of 5-LOX inhibitors that could be developed.

Inhibition of Lipoxygenases Showed No Benefit for the Musculoskeletal System in Estrogen Deficient Rats

BackgroundIn previous studies, we reported the beneficial impact of two lipoxygenase-inhibitors, Baicalein and Zileuton, on osteoporotic bone in a postmenopausal rat model. Whereas subcutaneous Baicalein predominantly improved cortical bone, Zileuton enhanced vertebral and femoral trabecular bone. In this study, we aimed to reveal whether the oral administration of Baicalein caused similar effects on bone and whether a combined administration of Baicalein and Zileuton could act synergistically to ameliorate the formerly reported effects in the musculoskeletal system.MethodsWe treated ovariectomized (OVX) female Sprague-Dawley rats either with Baicalein (10mg/kg BW), Zileuton (10mg/kg BW) or a combination of both (each 10mg/kg BW) for 13 weeks and compared with untreated OVX and NON-OVX groups (n=12-16 rats per group). Lumbar vertebral bodies and femora were analyzed. Tibiae were osteotomized, plate-stabilized (at week 8 after OVX) and likewise analyzed by biomechanical, histological, micro-computed tomographical and ashing tests. The skeletal muscle structure was analyzed.ResultsOral administration of Baicalein did not confirm the reported favorable cortical effects in neither vertebra nor femur. Zileuton showed a beneficial effect on trabecular vertebra, while the femur was negatively affected. Callus formation was enhanced by all treatments; however, its density and biomechanical properties were unaltered. Lipoxygenase inhibition did not show a beneficial effect on skeletal muscle. The combination therapy did not ameliorate OVX-induced osteoporosis but induced even more bone loss.ConclusionsThe preventive anti-osteoporotic treatments with two lipoxygenase inhibitors applied either alone or in combination showed no benefit for the musculoskeletal system in estrogen deficient rats.

Potential Anticancer Lipoxygenase Inhibitors from the Red Sea-Derived Brown Algae Sargassum cinereum: An In-Silico-Supported In-Vitro Study

LC-MS-assisted metabolomic profiling of the Red Sea-derived brown algae Sargassum cinereum “Sargassaceae” dereplicated eleven compounds 1–11. Further phytochemical investigation afforded two new aryl cresol 12–13, along with eight known compounds 14–21. Both new metabolites, along with 19, showed moderate in vitro antiproliferative activity against HepG2, MCF-7, and Caco-2. Pharmacophore-based virtual screening suggested both 5-LOX and 15-LOX as the most probable target linked to their observed antiproliferative activity. The in vitro enzyme assays revealed 12 and 13 were able to inhibit 5-LOX more preferentially than 15-LOX, while 19 showed a convergent inhibitory activity toward both enzymes. Further in-depth in silico investigation revealed the molecular interactions inside both enzymes’ active sites and explained the varying inhibitory activity for 12 and 13 toward 5-LOX and 15-LOX.