Title : Therapeutic modulators mediated neuroprotective potential in experimental multiple sclerosis: Evidence from CSF, blood markers, brain samples and in-silico investigations
Abstract:
Multiple sclerosis (MS) is a debilitating, inflammatory and demyelinating disease of the central nervous system influenced by environmental and genetic factors. Around 2.8 million people worldwide are affected in MS due to its challenging diagnosis and treatment. Our study investigates the role of the various cellular and molecular targets such as SIRT-1/mitochondrial ETC/Coenzyme-Q10; PI3K/AKT/m-TOR; Nrf2/OH-1; JAK/STAT-3/PPAR-gamma; cJNK/p38MAPK, IGF-1/GLP-1; and ERK1/2 MAPK signaling pathways in the progression of multiple sclerosis. Inflammation and demyelination can be caused by dysregulation of these pathways. Modulating these above mentioned cellular and molecular targets associated signaling pathways may offer therapeutic potential for multiple sclerosis. Therapeutic modulators includes solanesol; chrysophanol; acetyl-11-keto-beta boswellic acid; guggulsterone; apigenin; 4- hyroxyisoleucine; and alpha-mangostin has been investigated for its therapeutic potential in our laboratory. These natural active phytochemicals have been studied for its neuroprotective effect in neurodegenerative diseases and is shown to inhibit inflammatory responses and promote regeneration of damaged myelin sheaths, indicating its potential efficacy in treating multiple sclerosis. These phytochemicals exerts its neuroprotective effect by modulating the expression of cellular and molecular targets. Fingolimod; memantine, baclofen; simvastatin, and donepezil was also administered to compare the efficacy of therapeutic modulators potential in MS. In addition, these active phytoconstituents altered the CBC profile, intensifying the clinical presentation of multiple sclerosis. In addition, we evaluated the diagnostic potential of various biological samples, including CSF, blood plasma, and brain homogenates (striatum, cortex, hippocampus, and midbrain). These samples were used to evaluate the neurochemical changes caused by neurobehavioral alterations during the progression of multiple sclerosis. These results indicate that therapeutic modulators treatment ameliorated multiple sclerosis and that the mechanism underlying these effects may be closely related to the modulation of the cellular and molecular signaling pathway, and may further help in the diagnosis and progression of MS in early stage of life.
Keywords: Multiple Sclerosis; Demyelination; Phytochemicals, Myelin; Oligodendrocytes; Neuroprotection
