Harmine and 7,8-dihydroxyflavone synergistically suitable for amyotrophic lateral sclerosis management: An in silico study

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease characterized by progressive degeneration of both upper and lower motor neurons, resulting in paralysis eventually leads to death from respiratory failure typically within 3 5 years symptom onset. The aim this work was predict the pharmacokinetics identify unique protein targets that are associated with potential anti-ALS phytochemicals FDA-approved drugs, silico approaches.
 Materials methods: Standard computational tools (webserver software) were used, methods used clustering analysis, molecular target predictions, docking simulation.
 Results discussion: results show riluzole, β-asarone, cryptotanshinone, harmine 7,8-dihydroxyflavone have similar properties. Riluzole 95% probability on norepinephrine transporter. Huperzine-A cryptotanshinone 100% acetylcholinesterase. shows 35% several carbonic anhydrases, 40% CYP19A1, inhibitor nuclear factor kappa B kinase beta subunit neurotrophic tyrosine receptor type 2, respectively. Harmine also dual specificity tyrosine-phosphorylation-regulated kinases, threonine-protein kinases (haspin PIM3), adrenergic receptors, cyclin-dependent (CDK5 CDK9), monoamine oxidase A, casein I delta, serotonin (CLK1, CLK2, CLK4), nischarin, Also, gene expression network possible involvement CDK1, CDK2, CDK4, ERK1, ERK2 MAPK14 signaling pathways. This study riluzole closely physicochemical properties as well targets, such transporter (SLC6A2). Harmine, huperzine-A could modulate acetylcholinesterase (AChE), which involved ALS-pathogenesis. impact anhydrases (CA) I, II, VII, IX, XII, XIV, help remediating ALS.
 Conclusion: Overall, found be superior combination can provide more effective treatment for ALS than current regime. Further needed validate predicted therapeutic identified model or clinical trials, using silico, vitro vivo techniques.
 Graphical abstract: