Department Of Pharmacology

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Author: search.filters.author.Kumar, SachinHas files: No

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    An Overview of the Pathophysiological Mechanisms of 3-Nitropropionic Acid (3-NPA) as a Neurotoxin in a Huntington's Disease Model and Its Relevance to Drug Discovery and Development
    (Springer, 2023-02-04T00:00:00) Upadhayay, Shubham; Yedke, Narhari Gangaram; Rahi, Vikrant; Singh, Surbhi; Kumar, Sachin; Arora, Anchal; Chandolia, Priyanka; Kaur, Prabhsharan; Kumar, Mandeep; Koshal, Prashant; Jamwal, Sumit; Kumar, Puneet
    Animal models are used to better understand the various mechanisms involved in the pathogenesis of diseases and explore potential pathways that will aid in discovering therapeutic targets. 3-Nitropropionic Acid (3-NPA) is a neurotoxin used to induce Huntington's disease (HD)-like symptoms in experimental animals. The 3-NPA is a fungus toxin that impairs the complex II (succinate dehydrogenase) activity of the mitochondria and reduces ATP synthesis, leading to excessive production of free radicals resulting in the degeneration of GABAergic medium spiny neurons (MSNs) in the striatum. This is characterized by motor impairments a key clinical manifestation of HD. 3-NPA has the potential to alter several cellular processes, including mitochondrial functions, oxidative stress, apoptosis, and neuroinflammation mimicking HD-like pathogenic conditions in animals. This review strives to provide a new insight towards the 3-NPA induced molecular dysfunctioning in developing an animal model of HD. Moreover, we summarise several preclinical studies that support the use of the 3-NPA-induced models for drug discovery and development in HD. This review is a collection of various articles that were published from 1977 to 2022 on Pubmed (1639), Web of Science (2139), and Scopus (2681), which are related to the 3-NPA induced animal model. Graphical Abstract: [Figure not available: see fulltext.] � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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    Trans-cinnamaldehyde mitigates rotenone-induced neurotoxicity via inhibiting oxidative stress in rats
    (Elsevier B.V., 2022-12-21T00:00:00) Kumar, Sandeep; Kumar, Sachin; Arthur, Richmond; Kumar, Puneet
    Background: The second most prevalent age-related brain condition, Parkinson's disease (PD) is characterised by the loss of neurons in the substantia nigra pars compacta (SNpc). It is associated with symptoms like bradykinesia, stiffness, tremor, and impaired postural responses. Motor dysfunction, and neurochemical imbalance, are involved in the pathophysiology of PD. It has been hypothesised that trans cinnamaldehyde (TCA) a component of Traditional Chinese Medicine (TCM) can ameliorate Parkinson-like symptoms by altering the levels of different biochemical markers and reverse motor impairments. This research sought to determine the neuroprotective effect of TCA against the neurotoxicity caused by rotenone. Basic Procedure: Rotenone (1.5 mg/kg/day; s.c. for 35 days) was given to rats to induce Parkinson-like symptoms. TCA (5, 10, and 20 mg/kg) and concomitant treatment of TCA (5 mg/kg) with L-NAME (10 mg/kg) were given one hour prior to rotenone administration. Every week until the 35th day, behavioral parameters (muscle coordination, spontaneous motor movement and gait abnormalities) were assessed using rotarod, actophotometer, and narrow beam apparatus respectfully. Rats were decapitated on the 35th day, the striatum and cortex were isolated for biochemical tests. Main findings: Rotenone treatment reduced body weight, altered motor coordination and reduced the oxidative defense system. Treatment with TCA significantly improved the alterations in antioxidant levels as well as behavioral parameters. Furthermore, L-NAME (nitric oxide synthase inhibitor) in combination with TCA had a more significant effect as compared to TCA alone, signifying a possible drug interaction. Principal conclusion: TCA could be employed as an adjuvant in PD management. � 2022 The Authors
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    Natural Products as an Alternative Therapy for Brain Tumors: From Bench To Bedside
    (Springer Singapore, 2022-09-28T00:00:00) Kumar, Sachin; Kumar, Mandeep; Bijalwan, Anjali; Sharma, Shubham; Kumar, Puneet
    Incremental elevation in the trends of a brain tumor in recent years accounts for 5% adult population, whereas the number exceeds 70% in the case of children. Evidence reveals an eventual metastasize of 20%-30% of malignant tumors to the brain�s different regions. Compression in the brain tissue and elevated intracranial pressure mediated by benign and malignant tumors contributed to severe consequences like the central nervous system (CNS) damage or even imperil the patient�s life. Despite multiple therapeutic strategies in the market, none of the drugs are fully effective and safe. Strategic advancement indicates chemotherapy as a treatment of choice for critical conditions like brain tumors, but the chemotherapy drugs toxicity is still a major therapeutic hurdle. Plants and their derived natural products are one of the most emerging targets to strike against brain tumors. Analogs of several natural products are already demonstrated as antitumor in nature, and day by day, advancements unfold various other plant and plant derivatives having such antitumor activity. This chapter aims to underline and emphasize the antitumor agents, which can target brain tumors procured from the natural origin such as natural products and their analogs. The available data on different plants and isolated compounds of natural origin used to reduce and arrest brain tumors is also discussed here. � Springer Nature Singapore Pte Ltd. 2022.
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    Role of vitamins and minerals as immunity boosters in COVID-19
    (Springer Science and Business Media Deutschland GmbH, 2021-06-10T00:00:00) Kumar, Puneet; Kumar, Mandeep; Bedi, Onkar; Gupta, Manisha; Kumar, Sachin; Jaiswal, Gagandeep; Rahi, Vikrant; Yedke, Narhari Gangaram; Bijalwan, Anjali; Sharma, Shubham; Jamwal, Sumit
    Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) known as coronavirus disease (COVID-19), emerged in Wuhan, China, in December 2019. On March 11, 2020, it was declared a global pandemic. As the world grapples with COVID-19 and the paucity of clinically meaningful therapies, attention has been shifted to modalities that may aid in immune system strengthening. Taking into consideration that the COVID-19 infection strongly affects the immune system via multiple inflammatory responses, pharmaceutical companies are working to develop targeted drugs and vaccines against SARS-CoV-2 COVID-19. A balanced nutritional diet may play an essential role in maintaining general wellbeing by controlling chronic infectious diseases. A balanced diet including vitamin A, B, C, D, E, and K, and some micronutrients such as zinc, sodium, potassium, calcium, chloride, and phosphorus may be beneficial in various infectious diseases. This study aimed to discuss and present recent data regarding the role of vitamins and minerals in the treatment of COVID-19. A deficiency of these vitamins and minerals in the plasma concentration may lead to a reduction in the good performance of the immune system, which is one of the constituents that lead to a poor immune state. This is a narrative review concerning the features of the COVID-19 and data related to the usage of vitamins and minerals as preventive measures to decrease the morbidity and mortality rate in patients with COVID-19. � 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
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    The beneficial effect of rice bran extract against rotenone-induced experimental parkinson�s disease in rats
    (Bentham Science Publishers, 2021-02-12T00:00:00) Kumar, Sachin; Kumar, Puneet
    Background: Neurodegenerative diseases have become an increasing cause of various disabilities worldwide, followed by aging, including Parkinson�s disease (PD). Parkinson�s disease is a degenerative brain disorder distinguished by growing motor & non-motor failure due to the de-generation of medium-sized spiked neurons in the striatum region. Rotenone is often employed to originate the animal model of PD. It is a powerful blocker of mitochondrial complex-I, mitochon-drial electron transport chain that reliably produces Parkinsonism-like symptoms in rats. Rice bran (RB) is very rich in polyunsaturated fatty acids (PUFA) and nutritionally beneficial compounds, such as ?-oryzanol, tocopherols, and tocotrienols and sterols are believed to have favorable out-comes on oxidative stress & mitochondrial function. Objective: The present study has been designed to explore RB extract�s effect against rotenone-in-duced neurotoxicity in rats. Methods: In the present study, Rotenone (2 mg/kg, s.c) was administered systemically for 28 days. The hexane extract of RB was prepared using Soxhlation. Hexane extract (250 & 500 mg/kg) was administered per oral for 28 days in rotenone-treated groups. Behavioral parameters (grip strength, motor coordination, locomotion, and catalepsy) were conducted on the 7th, 14th, 21st, and 28th day. Animals were sacrificed on the 29th day for biochemical estimation in the striatum and cortex. Results: This study demonstrates significant alteration in behavioral parameters, oxidative burden (increased lipid peroxidation, nitrite concentration, and decreased glutathione, catalase, SOD) in rotenone-treated animals. Administration of hexane extract of RB prevented the behavioral, biochemical alterations induced by rotenone. The current research has been sketched to inspect RB ex-tract�s effect against rotenone-developed neurotoxicity in rats. Conclusion: The findings support that PD is associated with impairments in motor activity. The results also suggest that the nutraceutical rice bran that contains ?-oryzanol, Vitamin-E, ferulic acid etc., may underlie the adjuvant susceptibility towards rotenone-induced PD in experimental rats. � 2021 Bentham Science Publishers.