Abstract
Multiple sclerosis is a chronic autoimmune disorder that leads to the demyelination of nerve fibers, which is the major cause of non-traumatic disability all around the world. Herbal plants Nepeta hindustana L., Vitex negundo L., and Argemone albiflora L., in addition to anti-inflammatory and anti-oxidative effects, have shown great potential as neuroprotective agents. The study was aimed to develop a neuroprotective model to study the effectiveness of herbal plants (N. hindustana, V. negundo, and A. albiflora) against multiple sclerosis. The in vivo neuroprotective effects of ethanolic extracts isolated from N. hindustana, V. negundo, and A. albiflora were evaluated in lipopolysaccharides (LPS) induced multiple sclerosis Wistar rat model. The rat models were categorized into seven groups including group A as normal, B as LPS induced diseased group, while C, D, E, F, and G were designed as treatment groups. Histopathological evaluation and biochemical markers including stress and inflammatory (MMP-6, MDA, TNF-α, AOPPs, AGEs, NO, IL-17 and IL-2), antioxidant (SOD, GSH, CAT, GPx), DNA damage (Isop-2α, 8OHdG) as well as molecular biomarkers (RAGE, Caspase-8, p38) along with glutamate, homocysteine, acetylcholinesterase, and myelin binding protein (MBP) were investigated. The obtained data were analyzed using SPSS version 21 and GraphPad Prism 8.0. The different extract treated groups (C, D, E, F, G) displayed a substantial neuroprotective effect regarding remyelination of axonal terminals and oligodendrocytes migration, reduced lymphocytic infiltrations, and reduced necrosis of Purkinje cells. The levels of stress, inflammatory, and DNA damage markers were observed high in the diseased group B, which were reduced after treatments with plant extracts. The antioxidant activity was significantly reduced in diseased induced group B, however, their levels were raised after treatment with plant extract. Group F (a mélange of all the extracts) showed the most significant change among all other treatment groups (C, D, E, G). The communal dose of selected plant extracts regulates neurodegeneration at the cellular level resulting in restoration and remyelination of axonal neurons. Moreover, 400 mg/kg dose of three plants in conjugation (Group F) were found to be more effective in restoring the normal activities of all measured parameters than independent doses (Group C, D, E) and is comparable with standard drug nimodipine (Group G) clinically used for the treatment of multiple sclerosis. The present study, for the first time, reported the clinical evidence of N. hindustana, V. negundo, and A. albiflora against multiple sclerosis and concludes that all three plants showed remyelination as well neuroprotective effects which may be used as a potential natural neurotherapeutic agent against multiple sclerosis.
Highlights
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, which is characterized as episodes of inflammation, neurons demyelination, and gliosis, with distinctive neuronal loss
The body mass decreased notably after the LPS induction which improved after the treatment was given
The current study has reported that the levels of various antioxidants including Super Oxide Dismutase (SOD), CAT, GSH have been drastically decreased at disease induction in all groups as evident from previous studies [61,62] and their levels were significantly restored after treatment with the selected plant extracts which is concurrent with the study of Kumar et al [63]
Summary
Multiple sclerosis (MS) is a neurodegenerative autoimmune disease, which is characterized as episodes of inflammation, neurons demyelination, and gliosis, with distinctive neuronal loss. It may be relapse-remitting or sometimes, progressive [1,2]. MS is known as the utmost reason for the neuronal disability that may disturb various systems in the body, resulting in countless neurological symptoms along with several comorbidities. These include visual disturbance, ataxia, sensory loss, double-vision, impaired balance, and muscle-weakness and affect the life expectancy [4]. The Food and Drug Administration (FDA) and European Medicines Agency (EMA) have approved Alemtuzumab, dimethyl fumarate, glatiramer-acetate, pegylated interferon-β, and vitamin-D for treatment of MS [10–14]
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