Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy
Neuropathic pain refers to a lesion or disease of peripheral and/or central somatosensory neurons and is an important body response to actual or potential nerve damage. We investigated the therapeutic potential of two thiadiazine-thione [TDT] derivatives, 2-(5-propyl-6-thioxo-1, 3, 5-thiadiazinan-3-...
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Frontiers Media S.A.
2021-12-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2021.728128/full |
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| author | Sonia Qureshi Gowhar Ali Gowhar Ali Muhammad Idrees Muhammad Idrees Tahir Muhammad Tahir Muhammad Il-Keun Kong Il-Keun Kong Il-Keun Kong Muzaffar Abbas Muhammad Ishaq Ali Shah Sajjad Ahmad Robert D. E. Sewell Sami Ullah |
| author_facet | Sonia Qureshi Gowhar Ali Gowhar Ali Muhammad Idrees Muhammad Idrees Tahir Muhammad Tahir Muhammad Il-Keun Kong Il-Keun Kong Il-Keun Kong Muzaffar Abbas Muhammad Ishaq Ali Shah Sajjad Ahmad Robert D. E. Sewell Sami Ullah |
| author_sort | Sonia Qureshi |
| collection | DOAJ |
| description | Neuropathic pain refers to a lesion or disease of peripheral and/or central somatosensory neurons and is an important body response to actual or potential nerve damage. We investigated the therapeutic potential of two thiadiazine-thione [TDT] derivatives, 2-(5-propyl-6-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT1] and 2-(5-propyl-2-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT2] against CCI (chronic constriction injury)-induced neuroinflammation and neuropathic pain. Mice were used for assessment of acute toxicity of TDT derivatives and no major toxic/bizarre responses were observed. Anti-inflammatory activity was assessed using the carrageenan test, and both TDT1 and TDT2 significantly reduced carrageenan-induced inflammation. We also used rats for the induction of CCI and performed allodynia and hyperalgesia-related behavioral tests followed by biochemical and morphological analysis using RT-qPCR, immunoblotting, immunohistochemistry and immunofluorescence. Our findings revealed that CCI induced clear-cut allodynia and hyperalgesia which was reversed by TDT1 and TDT2. To determine the function of TDT1 and TDT2 in glia-mediated neuroinflammation, Iba1 mRNA and protein levels were measured in spinal cord tissue sections from various experimental groups. Interestingly, TDT1 and TDT2 substantially reduced the mRNA expression and protein level of Iba1, implying that TDT1 and TDT2 may mitigate CCI-induced astrogliosis. In silico molecular docking studies predicted that both compounds had an effective binding affinity for TNF-α and COX-2. The compounds interactions with the proteins were dominated by both hydrogen bonding and van der Waals interactions. Overall, these results suggest that TDT1 and TDT2 exert their neuroprotective and analgesic potentials by ameliorating CCI-induced allodynia, hyperalgesia, neuroinflammation and neuronal degeneration in a dose-dependent manner. |
| first_indexed | 2024-12-24T11:06:21Z |
| format | Article |
| id | doaj.art-debc8eb755234afe82adc1349e940c3d |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-24T11:06:21Z |
| publishDate | 2021-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-debc8eb755234afe82adc1349e940c3d2022-12-21T16:58:37ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992021-12-011410.3389/fnmol.2021.728128728128Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced NeuropathySonia Qureshi0Gowhar Ali1Gowhar Ali2Muhammad Idrees3Muhammad Idrees4Tahir Muhammad5Tahir Muhammad6Il-Keun Kong7Il-Keun Kong8Il-Keun Kong9Muzaffar Abbas10Muhammad Ishaq Ali Shah11Sajjad Ahmad12Robert D. E. Sewell13Sami Ullah14Department of Pharmacy, University of Peshawar, Peshawar, PakistanDepartment of Pharmacy, University of Peshawar, Peshawar, PakistanLaboratory of Neurogenomics and Novel Therapies, The Ken and Ruth Davee Department of Neurology, Department of Neurology and Clinical Neurosciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, South KoreaInstitute of Agriculture and Life Science, Gyeongsang National University, Jinju, South KoreaMolecular Neuropsychiatry and Development (MiND) Lab, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, ON, CanadaInstitute of Medical Science, University of Toronto, Toronto, ON, CanadaDivision of Applied Life Science (BK21 Four), Gyeongsang National University, Jinju, South KoreaInstitute of Agriculture and Life Science, Gyeongsang National University, Jinju, South KoreaThe Kingkong Co., Ltd., Gyeongsang National University, Jinju, South KoreaFaculty of Pharmacy, Capital University of Science & Technology, Islamabad, PakistanDepartment of Chemistry, Abdul Wali Khan University, Mardan, Pakistan0Department of Health and Biological Sciences, Abasyn University, Peshawar, Pakistan1School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, United KingdomDepartment of Pharmacy, University of Peshawar, Peshawar, PakistanNeuropathic pain refers to a lesion or disease of peripheral and/or central somatosensory neurons and is an important body response to actual or potential nerve damage. We investigated the therapeutic potential of two thiadiazine-thione [TDT] derivatives, 2-(5-propyl-6-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT1] and 2-(5-propyl-2-thioxo-1, 3, 5-thiadiazinan-3-yl) acetic acid [TDT2] against CCI (chronic constriction injury)-induced neuroinflammation and neuropathic pain. Mice were used for assessment of acute toxicity of TDT derivatives and no major toxic/bizarre responses were observed. Anti-inflammatory activity was assessed using the carrageenan test, and both TDT1 and TDT2 significantly reduced carrageenan-induced inflammation. We also used rats for the induction of CCI and performed allodynia and hyperalgesia-related behavioral tests followed by biochemical and morphological analysis using RT-qPCR, immunoblotting, immunohistochemistry and immunofluorescence. Our findings revealed that CCI induced clear-cut allodynia and hyperalgesia which was reversed by TDT1 and TDT2. To determine the function of TDT1 and TDT2 in glia-mediated neuroinflammation, Iba1 mRNA and protein levels were measured in spinal cord tissue sections from various experimental groups. Interestingly, TDT1 and TDT2 substantially reduced the mRNA expression and protein level of Iba1, implying that TDT1 and TDT2 may mitigate CCI-induced astrogliosis. In silico molecular docking studies predicted that both compounds had an effective binding affinity for TNF-α and COX-2. The compounds interactions with the proteins were dominated by both hydrogen bonding and van der Waals interactions. Overall, these results suggest that TDT1 and TDT2 exert their neuroprotective and analgesic potentials by ameliorating CCI-induced allodynia, hyperalgesia, neuroinflammation and neuronal degeneration in a dose-dependent manner.https://www.frontiersin.org/articles/10.3389/fnmol.2021.728128/fullthiadiazine-thioneneuropathic painallodynia/hyperalgesiaastrocytetumor necrotic factor-alpha |
| spellingShingle | Sonia Qureshi Gowhar Ali Gowhar Ali Muhammad Idrees Muhammad Idrees Tahir Muhammad Tahir Muhammad Il-Keun Kong Il-Keun Kong Il-Keun Kong Muzaffar Abbas Muhammad Ishaq Ali Shah Sajjad Ahmad Robert D. E. Sewell Sami Ullah Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy Frontiers in Molecular Neuroscience thiadiazine-thione neuropathic pain allodynia/hyperalgesia astrocyte tumor necrotic factor-alpha |
| title | Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy |
| title_full | Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy |
| title_fullStr | Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy |
| title_full_unstemmed | Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy |
| title_short | Selected Thiadiazine-Thione Derivatives Attenuate Neuroinflammation in Chronic Constriction Injury Induced Neuropathy |
| title_sort | selected thiadiazine thione derivatives attenuate neuroinflammation in chronic constriction injury induced neuropathy |
| topic | thiadiazine-thione neuropathic pain allodynia/hyperalgesia astrocyte tumor necrotic factor-alpha |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2021.728128/full |
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