Department Of Pharmacology

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    Gut microbiota dysbiosis and Huntington's disease: Exploring the gut-brain axis and novel microbiota-based interventions
    (Elsevier Inc., 2023-06-24T00:00:00) Sharma, Garvita; Biswas, Shristi Saroj; Mishra, Jayapriya; Navik, Umashanker; Kandimalla, Ramesh; Reddy, P. Hemachandra; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
    Huntington's disease (HD) is a complex progressive neurodegenerative disorder affected by genetic, environmental, and metabolic factors contributing to its pathogenesis. Gut dysbiosis is termed as the alterations of intestinal microbial profile. Emerging research has highlighted the pivotal role of gut dysbiosis in HD, focusing on the gut-brain axis as a novel research parameter in science. This review article provides a comprehensive overview of gut microbiota dysbiosis and its relationship with HD and its pathogenesis along with the future challenges and opportunities. The focuses on the essential mechanisms which link gut dysbiosis to HD pathophysiology including neuroinflammation, immune system dysregulation, altered metabolites composition, and neurotransmitter imbalances. We also explored the impacts of gut dysbiosis on HD onset, severity, and symptoms such as cognitive decline, motor dysfunction, and psychiatric symptoms. Furthermore, we highlight recent advances in therapeutics including microbiota-based therapeutic approaches, including dietary interventions, prebiotics, probiotics, fecal microbiota transplantation, and combination therapies with conventional HD treatments and their applications in managing HD. The future challenges are also highlighted as the heterogeneity of gut microbiota, interindividual variability, establishing causality between gut dysbiosis and HD, identifying optimal therapeutic targets and strategies, and ensuring the long-term safety and efficacy of microbiota-based interventions. This review provides a better understanding of the potential role of gut microbiota in HD pathogenesis and guides the development of novel therapeutic approaches. � 2023 Elsevier Inc.
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    Bacillus calmette gaurine vaccine ameliorates the neurotoxicity of quinolinic acid in rats via the modulation of antioxidant, inflammatory and apoptotic markers
    (Elsevier B.V., 2023-05-11T00:00:00) Yedke, Narhari Gangaram; Arthur, Richmond; Kumar, Puneet
    A mutation in the Huntingtin gene causes �Huntington's disease, which presents as a motor and behavioral impairment. Due to the limited drug therapy for this disease, scientists are constantly searching for newer and alternative drugs that may either retard or prevent the progress of the disease. This study aims to explore the neuroprotective potential of Bacillus Calmette Gaurine (BCG) vaccine against quinolinic acid-induced (QA) neurotoxicity in rats. QA (200 nmol/2 �l, i.s) was injected bilaterally into the rat striatum, after which a single dose of BCG (2 � 10^7, cfu) was given to the rats. Animals were assessed for behavioral parameters on the 14th and 21st days. On the 22nd day, animals were sacrificed, brains were harvested, and striatum was separated to evaluate biochemical, inflammatory, and apoptotic mediators. Histopathological studies were performed using Hematoxyline and Eosin staining to assess neuronal morphology. BCG treatment reversed motor abnormalities, reduced oxidative stress and neuroinflammatory markers, apoptotic mediators and striatal lesions induced by QA treatment. In conclusion, treat' 'ing rats with BCG vaccine (2 � 10^7, cfu) mitigated the quinolinic acid-induced Huntington's disease-like symptoms. Hence, BCG vaccine (2 �10^7, cfu) could be used as an adjuvant in managing HD. � 2023 Elsevier B.V.
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    Antiplatelet drugs: Potential therapeutic options for the management of neurodegenerative diseases
    (John Wiley and Sons Inc, 2023-05-03T00:00:00) Beura, Samir K.; Dhapola, Rishika; Panigrahi, Abhishek R.; Yadav, Pooja; Kumar, Reetesh; Reddy, Dibbanti H.; Singh, Sunil K.
    The blood platelet plays an important role but often remains under-recognized in several vascular complications and associated diseases. Surprisingly, platelet hyperactivity and hyperaggregability have often been considered the critical risk factors for developing vascular dysfunctions in several neurodegenerative diseases (NDDs) like Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis. In addition, platelet structural and functional impairments promote prothrombotic and proinflammatory environment that can aggravate the progression of several NDDs. These findings provide the rationale for using antiplatelet agents not only to prevent morbidity but also to reduce mortality caused by NDDs. Therefore, we thoroughly review the evidence supporting the potential pleiotropic effects of several novel classes of synthetic antiplatelet drugs, that is, cyclooxygenase inhibitors, adenosine diphosphate receptor antagonists, protease-activated receptor blockers, and glycoprotein IIb/IIIa receptor inhibitors in NDDs. Apart from this, the review also emphasizes the recent developments of selected natural antiplatelet phytochemicals belonging to key classes of plant-based bioactive compounds, including polyphenols, alkaloids, terpenoids, and flavonoids as potential therapeutic candidates in NDDs. We believe that the broad analysis of contemporary strategies and specific approaches for plausible therapeutic treatment for NDDs presented in this review could be helpful for further successful research in this area. � 2023 Wiley Periodicals LLC.
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    Berberine Ameliorate Haloperidol and 3-Nitropropionic Acid-Induced Neurotoxicity in Rats
    (Springer, 2022-07-25T00:00:00) Kadir, Abdul; Singh, Jasdeep; Rahi, Vikrant; Kumar, Puneet
    Berberine due to its antioxidant properties, has been used around the globe significantly to treat several brain disorders. Also, oxidative stress is a pathological hallmark in neurodegenerative diseases like Huntington�s disease (HD) and Tardive dyskinesia (TD). Berberine an alkaloid from plants has been reported to have neuroprotective potential in several animal models of neurodegenerative diseases. Hence, this study aims to evaluate the neuroprotective effect of berberine in the animal model of 3-nitropropionic acid (3-NP) induced HD and haloperidol induced tardive dyskinesia with special emphasis on its antioxidant property. The study protocol was divided into 2 phases, first phase involved the administration of 3-NP and berberine at the dose of (25, 50, and 100�mg/kg) intraperitoneally (i.p) and orally (p.o.) respectively for 21�days, and the following parameters (rotarod, narrow beam walk and photoactometer) as a measure of motor activity and striatal and cortical levels of (LPO, GSH, SOD, catalase, and nitrate) evaluated as a measure of oxidative stress were assessed for HD. Similarly in the second phase, TD was induced by using haloperidol, for 21�days and berberine at the dose of (25, 50, and 100�mg/kg) was administered, and both physical and biochemical parameters were assessed as mentioned for the HD study. The resultant�data indicated that berberine attenuate 3-NP and haloperidol-induced behavioral changes and improved the antioxidant capcity in rodents. Hence berberine might be a novel therapeutic candidate to manage TD & HD. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.