Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease
Huntington’s disease (HD) is distinguished by a triple repeat of CAG in exon 1, an increase in poly Q in the Htt gene, and a loss of GABAergic medium spiny neurons (MSN) in the striatum and white matter of the cortex. Mitochondrial ETC-complex dysfunctions are involved in the pathogenesis of HD, inc...
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2022-11-01
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| author | Thamer H. Albekairi Arzoo Kamra Sudeep Bhardwaj Sidharth Mehan Aditi Giri Manisha Suri Abdulrahman Alshammari Metab Alharbi Abdullah F. Alasmari Acharan S Narula Reni Kalfin |
| author_facet | Thamer H. Albekairi Arzoo Kamra Sudeep Bhardwaj Sidharth Mehan Aditi Giri Manisha Suri Abdulrahman Alshammari Metab Alharbi Abdullah F. Alasmari Acharan S Narula Reni Kalfin |
| author_sort | Thamer H. Albekairi |
| collection | DOAJ |
| description | Huntington’s disease (HD) is distinguished by a triple repeat of CAG in exon 1, an increase in poly Q in the Htt gene, and a loss of GABAergic medium spiny neurons (MSN) in the striatum and white matter of the cortex. Mitochondrial ETC-complex dysfunctions are involved in the pathogenesis of HD, including neuronal energy loss, synaptic neurotrophic decline, neuronal inflammation, apoptosis, and grey and white matter destruction. A previous study has demonstrated that beta Boswellic acid (β-BA), a naturally occurring phytochemical, has several neuroprotective properties that can reduce pathogenic factors associated with various neurological disorders. The current investigation aimed to investigate the neuroprotective potential of β-BA at oral doses of 5, 10, and 15 mg/kg alone, as well as in conjunction with the potent antioxidant vitamin E (8 mg/kg, orally) in 3-NP-induced experimental HD rats. Adult Wistar rats were separated into seven groups, and 3-NP, at a dose of 10 mg/kg, was orally administered to each group of adult Wistar rats beginning on day 1 and continuing through day 14. The neurotoxin 3-NP induces neurodegenerative, g, neurochemical, and pathological alterations in experimental animals. Continuous injection of 3-NP, according to our results, aggravated HD symptoms by suppressing ETC-complex-II, succinate dehydrogenase activity, and neurochemical alterations. β-BA, when taken with vitamin E, improved behavioural dysfunctions such as neuromuscular and motor impairments, as well as memory and cognitive abnormalities. Pharmacological treatments with β-BA improved and restored ETC complexes enzymes I, II, and V levels in brain homogenates. β-BA treatment also restored neurotransmitter levels in the brain while lowering inflammatory cytokines and oxidative stress biomarkers. β-BA’s neuroprotective potential in reducing neuronal death was supported by histopathological findings in the striatum and cortex. As a result, the findings of this research contributed to a better understanding of the potential role of natural phytochemicals β-BA in preventing neurological illnesses such as HD. |
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| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T19:15:10Z |
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| spelling | doaj.art-63b7471cb6064340a082f94b829826562023-11-24T03:52:03ZengMDPI AGBiomedicines2227-90592022-11-011011286610.3390/biomedicines10112866Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s DiseaseThamer H. Albekairi0Arzoo Kamra1Sudeep Bhardwaj2Sidharth Mehan3Aditi Giri4Manisha Suri5Abdulrahman Alshammari6Metab Alharbi7Abdullah F. Alasmari8Acharan S Narula9Reni Kalfin10Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology, Seth G.L. Bihani S.D. College of Technical Education, Institute of Pharmaceutical Sciences and Drug Research, Sri Ganganagar 335001, Rajasthan, IndiaDepartment of Pharmacology, Seth G.L. Bihani S.D. College of Technical Education, Institute of Pharmaceutical Sciences and Drug Research, Sri Ganganagar 335001, Rajasthan, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, IndiaDivision of Neuroscience, Department of Pharmacology, ISF College of Pharmacy (An Autonomous College), Moga 142001, Punjab, IndiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaNarula Research, LLC, 107 Boulder Bluff, Chapel Hill, NC 27516, USAInstitute of Neurobiology, Bulgarian Academy of Sciences, Acad. G. Bonchev St., Block 23, 1113 Sofia, BulgariaHuntington’s disease (HD) is distinguished by a triple repeat of CAG in exon 1, an increase in poly Q in the Htt gene, and a loss of GABAergic medium spiny neurons (MSN) in the striatum and white matter of the cortex. Mitochondrial ETC-complex dysfunctions are involved in the pathogenesis of HD, including neuronal energy loss, synaptic neurotrophic decline, neuronal inflammation, apoptosis, and grey and white matter destruction. A previous study has demonstrated that beta Boswellic acid (β-BA), a naturally occurring phytochemical, has several neuroprotective properties that can reduce pathogenic factors associated with various neurological disorders. The current investigation aimed to investigate the neuroprotective potential of β-BA at oral doses of 5, 10, and 15 mg/kg alone, as well as in conjunction with the potent antioxidant vitamin E (8 mg/kg, orally) in 3-NP-induced experimental HD rats. Adult Wistar rats were separated into seven groups, and 3-NP, at a dose of 10 mg/kg, was orally administered to each group of adult Wistar rats beginning on day 1 and continuing through day 14. The neurotoxin 3-NP induces neurodegenerative, g, neurochemical, and pathological alterations in experimental animals. Continuous injection of 3-NP, according to our results, aggravated HD symptoms by suppressing ETC-complex-II, succinate dehydrogenase activity, and neurochemical alterations. β-BA, when taken with vitamin E, improved behavioural dysfunctions such as neuromuscular and motor impairments, as well as memory and cognitive abnormalities. Pharmacological treatments with β-BA improved and restored ETC complexes enzymes I, II, and V levels in brain homogenates. β-BA treatment also restored neurotransmitter levels in the brain while lowering inflammatory cytokines and oxidative stress biomarkers. β-BA’s neuroprotective potential in reducing neuronal death was supported by histopathological findings in the striatum and cortex. As a result, the findings of this research contributed to a better understanding of the potential role of natural phytochemicals β-BA in preventing neurological illnesses such as HD.https://www.mdpi.com/2227-9059/10/11/2866β-Boswellic acid (β-BA)Huntington’s disease (HD)mitochondrial ETC-complexes3-nitropropionic acid (3-NP)neuroprotection |
| spellingShingle | Thamer H. Albekairi Arzoo Kamra Sudeep Bhardwaj Sidharth Mehan Aditi Giri Manisha Suri Abdulrahman Alshammari Metab Alharbi Abdullah F. Alasmari Acharan S Narula Reni Kalfin Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease Biomedicines β-Boswellic acid (β-BA) Huntington’s disease (HD) mitochondrial ETC-complexes 3-nitropropionic acid (3-NP) neuroprotection |
| title | Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease |
| title_full | Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease |
| title_fullStr | Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease |
| title_full_unstemmed | Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease |
| title_short | Beta-Boswellic Acid Reverses 3-Nitropropionic Acid-Induced Molecular, Mitochondrial, and Histopathological Defects in Experimental Rat Model of Huntington’s Disease |
| title_sort | beta boswellic acid reverses 3 nitropropionic acid induced molecular mitochondrial and histopathological defects in experimental rat model of huntington s disease |
| topic | β-Boswellic acid (β-BA) Huntington’s disease (HD) mitochondrial ETC-complexes 3-nitropropionic acid (3-NP) neuroprotection |
| url | https://www.mdpi.com/2227-9059/10/11/2866 |
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