Department Of Pharmacology
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Item Calcium channelopathies in neurodegenerative disorder: an untold story of RyR and SERCA(Taylor and Francis Ltd., 2023-11-16T00:00:00) Dhureja, Maanvi; Arthur, Richmond; Soni, Divya; Upadhayay, Shubham; Temgire, Pooja; Kumar, PuneetIntroduction: Recent neuroscience breakthroughs have shed light on the sophisticated relationship between calcium channelopathies and movement disorders, exposing a previously undiscovered tale focusing on the Ryanodine Receptor (RyR) and the Sarco/Endoplasmic Reticulum Calcium ATPase (SERCA). Calcium signaling mainly orchestrates neural communication, which regulates synaptic transmission and total network activity. It has been determined that RyR play a significant role in managing neuronal functions, most notably in releasing intracellular calcium from the endoplasmic reticulum. Areas covered: It highlights the involvement of calcium channels such as RyR and SERCA in physiological and pathophysiological conditions. Expert opinion: Links between RyR and SERCA activity dysregulation, aberrant calcium levels, motor and cognitive dysfunction have brought attention to the importance of RyR and SERCA modulation in neurodegenerative disorders. Understanding the obscure function of these proteins will open up new therapeutic possibilities to address the underlying causes of neurodegenerative diseases. The unreported RyR and SERCA narrative broadens the understanding of calcium channelopathies in movement disorders and calls for more research into cutting-edge therapeutic approaches. � 2023 Informa UK Limited, trading as Taylor & Francis Group.Item Impact of noscapine on halting the progression of pentylenetetrazole induced kindling epilepsy in mice(John Wiley and Sons Inc, 2023-09-19T00:00:00) Gupta, Rishav; Soni, Divya; Upadhayay, Shubham; Dhureja, Maanvi; Kumar, PuneetEpilepsy is caused by an excessive recurrent excitatory neuronal firing, characterized by motor, psychomotor, and sensory impairments. Current therapies fail to produce 100% outcomes because of the complexity of the disease, poor diagnosis, and upsurge�to drug-resistant epilepsy. The study repurposed�the drug �noscapine��mainly known for its anti-tussive properties. For the management of epilepsy and its associated secondary complications. To confirm the effect of noscapine, adult mice were injected with pentylenetetrazole (PTZ) (35 mg/kg i.p.) on an alternate day for 29 days to induce epilepsy. Animals were pretreated with noscapine in three doses (5, 10, and 20 mg/kg i.p.) for 33 days. Various behavioural assessments like the open field test, Morris water maze, and tail suspension test were performed to observe animals' locomotor activity, spatial memory, and anxiety-depressive behaviour. On the 34th day, animals were sacrificed, and brains were removed for biochemical estimations. Prolonged PTZ treatment reduced locomotor, learning activity, and increased anxiety-depressive behaviour, which was further confirmed by reduced antioxidant levels such as reduced glutathione (GSH), superoxide dismutase (SOD), and catalase because of increased oxido-nitrosative stress, that is, malondialdehyde (MDA) and nitrite in the brain. In comparison, noscapine pretreatment attenuated PTZ-induced behavioural and biochemical changes in the animals. The results indicate that noscapine ameliorates the oxido-nitrosative stress. However, studies indicate that oxido-nitrosative stress is a significant concern for the GABAergic neurons and promotes the disease progression. Further studies are required to explore the molecular mechanism of noscapine, which might be a practical approach as a newer antiepileptic agent. � 2023 John Wiley & Sons Australia, Ltd.Item Opportunities and challenges in application of artificial intelligence in pharmacology(Springer Science and Business Media Deutschland GmbH, 2023-01-09T00:00:00) Kumar, Mandeep; Nguyen, T. P. Nhung; Kaur, Jasleen; Singh, Thakur Gurjeet; Soni, Divya; Singh, Randhir; Kumar, PuneetArtificial intelligence (AI) is a machine science that can mimic human behaviour like intelligent analysis of data. AI functions with specialized algorithms and integrates with deep and machine learning. Living in the digital world can generate a huge amount of medical data every day. Therefore, we need an automated and reliable evaluation tool that can make decisions more accurately and faster. Machine learning has the potential to learn, understand and analyse the data used in healthcare systems. In the last few years, AI is known to be employed in various fields in pharmaceutical science especially in pharmacological research. It helps in the analysis of preclinical (laboratory animals) and clinical (in human) trial data. AI also plays important role in various processes such as drug discovery/manufacturing, diagnosis of big data for disease identification, personalized treatment, clinical trial research, radiotherapy, surgical robotics, smart electronic health records, and epidemic outbreak prediction. Moreover, AI has been used in the evaluation of biomarkers and diseases. In this review, we explain various models and general processes of machine learning and their role in pharmacological science. Therefore, AI with deep learning and machine learning could be relevant in pharmacological research. � 2023, The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.Item Monkeypox infection: The past, present, and future(Elsevier B.V., 2022-10-29T00:00:00) Upadhayay, Shubham; Arthur, Richmond; Soni, Divya; Yadav, Poonam; Navik, UmaShanker; Singh, Randhir; Gurjeet Singh, Thakur; Kumar, PuneetMonkeypox is a zoonotic illness caused by the monkeypox virus (MPXV) that has a similar etiology to smallpox. The first case of monkeypox was reported in Western and Central Africa in 1971, and in 2003, there was an outbreak of monkeypox viruses outside Africa. According to the World Health Organization (WHO) and Center for Disease Control and Prevention (CDC), monkeypox is transmitted through direct contact with infected animals or persons exposed to infectious sores, scabs, or body fluids. Also, intimate contact between people during sex, kissing, cuddling, or touching parts of the body can result in the spreading of this disease. The use of the smallpox vaccine against monkeypox has several challenges and hence anti-virals such as cidofovir, brincidofovir, and tecovirimat have been used for the symptomatic relief of patients and reversing the lesion formation on the skin. Despite the recent outbreak of monkeypox most especially in hitherto non-endemic countries, there is still a lack of definitive treatment for monkeypox. In the present review, emphasis was focused on etiopathology, transmission, currently available therapeutic agents, and future targets that could be explored to halt the progression of monkeypox. From our review we can postulate that owing to the lack of a definitive cure to this reemerging disorder, there is a need for general awareness about the transmission as well as to develop appropriate diagnostic procedures, immunizations, and antiviral medication. � 2022 Elsevier B.V.Item Neuroprotective potential of Moringa oleifera mediated by NF-kB/Nrf2/HO-1 signaling pathway: A review(John Wiley and Sons Inc, 2022-10-07T00:00:00) Mundkar, Maroti; Bijalwan, Anjali; Soni, Divya; Kumar, PuneetMoringa oleifera is a traditional Indian herb belonging to the Moringaceae family, it is commonly known as the horse-radish tree, drumstick, or sahajna. In developing countries, Moringa is used as feed for both humans and animals due to its well-known antioxidant, anti-inflammatory, and anti-apoptotic properties owing to its several phytoconstituents including ?-carotene, quercetin, kaempferol, ascorbic acid, flavonoids, phenolic acid, rhamnose, glycosylates, glucomoringin, and isothiocyanates. These constituents help to maintain the brain antioxidant enzyme levels, mitochondrial functions, and neurogenesis, showing neuroprotective effects in several neurodegenerative disorders including Parkinson's Disease, Alzheimer's Disease, Huntington's Disease, and Amyotrophic lateral sclerosis. This review discusses various phytoconstituent of moringa and their therapeutic potential in various neurological disorders. Additionally, we also concise the safety and toxicity profile, of different molecular pathways involved in the neuroprotective effect of M. oleifera including M. oleifera nanoparticles for better therapeutic value. Practical applications: Several clinical and preclinical studies on Moringa oleifera have been conducted, and the outcomes indicate moringa could be used in the treatment of brain disorders. As a result, we conclude that moringa and its nanoformulations could be employed to treat neurological problems. In the future, M. oleifera phytoconstituents could be evaluated against specific signaling pathways, which could aid researchers in discovering their mechanism of action. Furthermore, the use of moringa as a nutraceutical owing to its myriad pharmacological potential will go a long way in boosting the economy of countries that grow moringa on a large scale. � 2022 Wiley Periodicals LLC.Item GSK-3?-mediated regulation of Nrf2/HO-1 signaling as a new therapeutic approach in the treatment of movement disorders(Springer Science and Business Media Deutschland GmbH, 2022-07-27T00:00:00) Soni, Divya; Kumar, PuneetMovement disorders are neurological conditions characterized by involuntary motor movements, such as dystonia, ataxia, chorea myoclonus, tremors, Huntington�s disease (HD), and Parkinson�s disease (PD). It is classified into two categories: hypokinetic and hyperkinetic movements. Globally, movement disorders are a major cause of death. The pathophysiological process is initiated by excessive ROS generation, mitochondrial dysfunction, neuroinflammation, and neurotransmitters imbalance that lead to motor dysfunction in PD and HD patients. Several endogenous targets including Nrf2 maintain oxidative balance in the body. Activation of Nrf2 signaling is regulated by the enzyme glycogen synthase kinase (GSK-3?). In the cytoplasm, inhibition of GSK-3? regulates cellular proliferation, homeostasis, and apoptotic process by stimulating the nuclear factor erythroid 2 (Nrf2) pathway which is involved in the elevation of the cellular antioxidant enzymes which controls the ROS generation. The activation of Nrf2 increases the expression of antioxidant response elements (ARE), such as (Hemeoxygenase-1) HO-1, which decreases excessive cellular stress, mitochondrial dysfunction, apoptosis, and neuronal degeneration, which is the major cause of motor dysfunction. The present review explores the GSK-3?-mediated neuroprotection in various movement disorders through the Nrf2/HO-1 antioxidant pathway. This review provides a�link between GSK-3? and the Nrf2/HO-1 signaling pathway in the treatment of PD and HD. In addition to that it highlights various GSK-3? inhibitors and the Nrf2/HO-1 activators, which exert robust neuroprotection against motor disorders. Therefore, the present review will help in the discovery of new therapy for PD and HD patients. � 2022, The Author(s) under exclusive licence to Maj Institute of Pharmacology Polish Academy of Sciences.