Metabolite Profiling and In Silico Analysis of Moringa oleifera Potential Multi-Target Neuroprotective Compounds for Traumatic Brain Injury

Traumatic brain injury (TBI) affects an estimated ۲۷.۰۸ million people globally. Because of its high morbidity and mortality, it continues to be a significant public health concern. Excessive inflammatory reactions and oxidative stress are hallmarks of the secondary damage phase of TBI. Proinflammatory cytokines like interleukin-۱β and tumor necrosis factor-alpha (TNF-α) contribute to glial activation, neuronal death, and disruption of the blood–brain barrier. The medicinal plant Moringa oleifera, which is rich in secondary metabolites, has been shown to activate the nuclear factor erythroid ۲-related factor ۲/heme oxygenase-۱ (Nrf۲/HO-۱) pathway and suppress nuclear factor Kappa-light-chain-enhancer of activated B cells (NF-κB) signaling. This enhances antioxidant defenses and lowers the production of proinflammatory cytokines. The research presented here used GC-MS profiling, and docking simulations were carried out against inducible nitric oxide synthase (iNOS; PDB ID: ۳HR۴), matrix metalloproteinase-۹ (MMP-۹; PDB ID: ۲OW۱), and TNF-α (PDB ID: ۲AZ۵). GC-MS analysis revealed ۵۳ chromatographic peaks in Moringa oleifera leaf extract, with triazine derivatives accounting for almost ۴۵% of the overall peak area. Using molecular docking, nine chosen compounds demonstrated stable interactions with TNF-α, MMP-۹, and iNOS, with validated docking accuracy (RMSD ≤ ۱.۷۲ Å) and rerank scores of −۶۳.۲۸ to −۸۳.۸۹, −۸۴.۹۰ to −۱۰۰.۷۳, and −۸۵.۹۹ to −۱۰۴.۰۸ kcal/mol, respectively. The above findings suggest that Moringa oleifera compounds have the potential to be candidates for multi-target neuroprotective therapies.

کلیدواژه ها:

Traumatic Brain Injury ، Metabolite profiling ، GC&ndash ، MS ، Molecular docking ، neuroinflammation