Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis,...
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Elsevier
2024-01-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024000811 |
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| author | Sarthak Sharma Sidharth Mehan Zuber Khan Ghanshyam Das Gupta Acharan S. Narula |
| author_facet | Sarthak Sharma Sidharth Mehan Zuber Khan Ghanshyam Das Gupta Acharan S. Narula |
| author_sort | Sarthak Sharma |
| collection | DOAJ |
| description | Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, and reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related factor 2), HO-1 (heme oxygenase 1), and TDP-43 (TAR-DNA-binding protein 43) accumulation in the context of ALS, as well as the modulation of these proteins by icariin (15 and 30 mg/kg, orally), a glycoside flavonoid with neuroprotective properties. Neuroprotective icariin activates SIRT-1, Nrf-2, and HO-1, mitigating inflammation and neuronal injury in neurodegenerative disorders. In-vivo and in-silico testing of experimental ALS models confirmed icariin efficacy in modulating these cellular targets. The addition of sirtinol 10 mg/kg, an inhibitor of SIRT-1, helps determine the effectiveness of icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, and LFB (Luxol fast blue) markers in various biological samples, including Cerebrospinal fluid (CSF), blood plasma, and brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, and Cerebellum). These results demonstrate that the administration of icariin ameliorates experimental ALS and that the mechanism underlying these benefits is likely related to regulating the SIRT-1, Nrf-2, and HO-1 signaling pathways. |
| first_indexed | 2024-03-08T09:01:36Z |
| format | Article |
| id | doaj.art-7f4cfd25ea9249118b56ad4173954a50 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-08T09:01:36Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-7f4cfd25ea9249118b56ad4173954a502024-02-01T06:34:31ZengElsevierHeliyon2405-84402024-01-01101e24050Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigationsSarthak Sharma0Sidharth Mehan1Zuber Khan2Ghanshyam Das Gupta3Acharan S. Narula4Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India), Moga, Punjab, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India), Moga, Punjab, India; Corresponding author. Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), NAAC Accredited ''A'' Grade College, GT Road, Ghal-Kalan, Moga – 142 001 Punjab, India.Division of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India), Moga, Punjab, IndiaDepartment of Pharmaceutics, ISF College of Pharmacy (Affiliated to IK Gujral Punjab Technical University, Jalandhar, Punjab, 144603, India), Moga, Punjab, IndiaNarula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USAAmyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease that causes significant neurodegeneration. Methylmercury (MeHg+) is a neurotoxin that induces axonal neurodegeneration and motor nerve degeneration by destroying oligodendrocytes, degenerating white matter, inducing apoptosis, excitotoxicity, and reducing myelin basic protein (MBP). This study examines the inhibition of SIRT-1 (silence information regulator 1), Nrf-2 (nuclear factor E2-related factor 2), HO-1 (heme oxygenase 1), and TDP-43 (TAR-DNA-binding protein 43) accumulation in the context of ALS, as well as the modulation of these proteins by icariin (15 and 30 mg/kg, orally), a glycoside flavonoid with neuroprotective properties. Neuroprotective icariin activates SIRT-1, Nrf-2, and HO-1, mitigating inflammation and neuronal injury in neurodegenerative disorders. In-vivo and in-silico testing of experimental ALS models confirmed icariin efficacy in modulating these cellular targets. The addition of sirtinol 10 mg/kg, an inhibitor of SIRT-1, helps determine the effectiveness of icariin. In this study, we also examined neurobehavioral, neurochemical, histopathological, and LFB (Luxol fast blue) markers in various biological samples, including Cerebrospinal fluid (CSF), blood plasma, and brain homogenates (Cerebral Cortex, Hippocampus, Striatum, mid-brain, and Cerebellum). These results demonstrate that the administration of icariin ameliorates experimental ALS and that the mechanism underlying these benefits is likely related to regulating the SIRT-1, Nrf-2, and HO-1 signaling pathways.http://www.sciencedirect.com/science/article/pii/S2405844024000811ALSMethylmercuryDemyelinationIcariinOligodendrocytesNeuroinflammation |
| spellingShingle | Sarthak Sharma Sidharth Mehan Zuber Khan Ghanshyam Das Gupta Acharan S. Narula Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations Heliyon ALS Methylmercury Demyelination Icariin Oligodendrocytes Neuroinflammation |
| title | Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations |
| title_full | Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations |
| title_fullStr | Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations |
| title_full_unstemmed | Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations |
| title_short | Icariin prevents methylmercury-induced experimental neurotoxicity: Evidence from cerebrospinal fluid, blood plasma, brain samples, and in-silico investigations |
| title_sort | icariin prevents methylmercury induced experimental neurotoxicity evidence from cerebrospinal fluid blood plasma brain samples and in silico investigations |
| topic | ALS Methylmercury Demyelination Icariin Oligodendrocytes Neuroinflammation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024000811 |
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