School Of Health Sciences
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Item Understanding the Cross-Talk between the Ceramide Biosynthetic Pathway and Mitochondrial Function in Multiple Sclerosis and Demyelinating Disorders(Wiley-Hindawi, 2023-10-12T00:00:00) Amarjeet; Babu, Raja; Mohapatra, Abhipsa; Pancholi, Bhaskaranand; Garabadu, Debapriya; Sharma, Anjali; Sharma, Ashwani; Azad, Md. A. K.Myelin is a spiral compilation of uniformly thick membranes around the axon in an alternating fashion, and it is formed by a complicated process known as myelination. Myelin sheaths are responsible for various physiological functions such as metabolism, rapid nerve conduction, and maintaining ionic and water homeostasis in the brain. Lipid is one of the major components in the myelin, which includes cholesterol, ceramide, and their derivatives, such as galactosylceramide, sulfatide, and gangliosides. Ceramide and its derivatives are synthesised by various ceramide biosynthetic pathways such as de novo, salvage, sphingomyelinase, and recycling of exogenous ceramide. At an appropriate level, ceramide facilitates the development of the nervous system, cell proliferation, autophagy, and apoptosis, which are responsible for normal functioning, but when the level is altered from normal, it results in mitochondrial dysfunction or cell death through autophagy and apoptosis. The ceramide level increases, especially in the mitochondria. Ceramide level increases in response to oxidative stress which is mediated by inflammatory cytokines. Due to mitochondrial dysfunction, an energy-deficient condition is created because of disruption in the electron transport chain, which results in the death of neurons and glial cells, which subsequently cause demyelination and degeneration of axon. Losing myelin while axons remain relatively intact is the characteristic feature of demyelinating diseases. The primary element of demyelinating disorder is damage, malfunction, failure, or death of mitochondria. These disturbances may occur due to direct or indirect interaction of ceramide with mitochondria. There are several risk factors for demyelination, such as viruses, bacteria, fungi, trauma, obesity, vitamin D deficiency, and genetic and environmental factors. Thus, the review is mainly aimed towards the interaction between ceramide and mitochondria during demyelination. � 2023 Amarjeet et al.Item Daidzein Attenuates Ovariectomy-Induced Cognitive Deficits by Improving Cortical Endothelial Function in Rats(Springer Science and Business Media Deutschland GmbH, 2023-07-17T00:00:00) Jaiswal, Salok; Goyal, Ahsas; Garabadu, DebapriyaThere have been reports of decreased vascular activity in memory-sensitive brain areas, which is thought to be a different approach to managing cognitive deficiencies in females with estrogen insufficiency. Daidzein, a plant-derived phytoestrogen, facilitates cerebral blood flow in normal animals and also improves vascular activity in the peripheral tissues of the ovariectomized animal. However, its neuroprotective activity in vascular function has not yet been established in ovariectomized animals. Hence, the present study explored the caveolin-1/eNOS/VEGF-mediated signaling in the anti-amnesic ability of daidzein in ovariectomized rats. On day 5 of the Morris water maze experiment, female rats with bilateral ovariectomy displayed amnesia as measured by an increase in both escape latency and time spent in the targeted quadrant. Further, ovariectomy reduced blood flow and the level of expression of vascular endothelial growth factor in rat cortical tissues. In addition, ovariectomy diminished the acetylcholine level, increased the acetylcholinesterase activity, and increased oxidative stress in rat cortical tissues. Daidzein attenuated ovariectomy-induced alterations in behavioral, vascular, cholinergic, and oxidative stress in the animals. These beneficial effects of daidzein were abolished with N-nitro-l-arginine methylester (L-NAME), which inhibits endothelial nitric oxide synthase, in the ovariectomized rat model. These observations emphasize the fact that daidzein potentially exerts anti-amnesic activity perhaps through the caveolin-1/eNOS/VEGF-mediated signaling pathway in ovariectomy-induced cognitive-deficit rats. Therefore, daidzein holds the potential as a therapeutic option for the treatment of cognitive deficits in postmenopausal women. Graphical Abstract: [Figure not available: see fulltext.]. � 2023, The Author(s) under exclusive licence to Sociedade Brasileira de Farmacognosia.Item Transferrin decorated PLGA encumbered moxifloxacin nanoparticles and in�vitro cellular studies(Taylor and Francis Ltd., 2023-03-05T00:00:00) Reddy, Gayathri Aparnasai; Handa, Mayank; Garabadu, Debapriya; Kumar, Ravindra; Kushawaha, Pramod Kumar; Shukla, RahulPurpose: Complicated intra-abdominal infection (cIAI) management involves administering antibiotics that destroy the cell wall and the genesis of bacterial lipopolysaccharide (LPS). During the infectious state, the expression of transferrin receptors upregulates on the intestinal epithelial cells, which are considered the site of infection. In the present research, transferrin decorated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) encapsulated moxifloxacin (MOX) were developed for possible targeting of the receptors in the colon. Significance: This study will explore more about the incorporation of transferrin as effective coating material in targeted drug delivery. Methods: Nanoparticles were prepared using nano-emulsification and surface modification with transferrin was done by layer-by-layer methodology and evaluated by powder X-ray diffraction (PXRD), differential scanning calorimeter (DSC), FTIR, SEM, antibacterial activity, and cellular uptake studies. Results: The formulated NPs exhibit a size of ?170 nm, PDI�?�0.25, zeta potential�??4.0 mV, drug loading�?�6.8%, and entrapment efficiency of 82%. Transferrin-decorated NPs exhibit tailored release for almost 12 h and in�vitro antibacterial activity for 14 h. The cellular uptake studies were done on a RAW264.7 cell line for better determination of transferrin uptake of fabricated NPs. Conclusion: The above study circumvents around the preparation of transferrin decorated PLGA encumbered MOX NPs intended for cIAI-induced sepsis. PLGA NPs provide tailored release of MOX with primary burst and followed by sustained release. These observations confines with antibacterial activity studies. The prepared transferrin-coated NPs were stable and effectively uptaken by RAW264.7 cells. However, future studies include the preclinical investigation of these NPs in sepsis-induced murine models. � 2023 Informa UK Limited, trading as Taylor & Francis Group.Item Bilayer fixed-dose combination tablet for curcumin microparticles and piroxicam and i n vitro evaluation(Newlands Press Ltd, 2023-02-07T00:00:00) Handa, Mayank; Kumar, Kamlesh; Garabadu, Debapriya; Kushawaha, Pramod Kumar; Shukla, RahulAim: In the present work, fixed-dose combination of bilayer tablets for piroxicam as and curcumin as immediate-release and sustained-release layer (SRL) respectively for management of inflammatory response. Materials & methods: The SRL include Curcumin polycaprolactone microparticles from spray drying. The tablet layers include Pearlitol 200SD, Microcrystalline cellulose PH101, Aerosil 200, talc each layer. Results: SEM studies confirm spherical microparticles. PXRD and DSC studies confirm the amorphous microparticles. In vitro studies exhibit, an immediate release and sustained release for Piroxicam and Curcumin after 2 h. Cellular uptake studies on RAW 264.7 cells confirm the complete internalization of microparticles. Conclusion: Therefore, it was concluded that microparticles can be formulated into a unit dosage form for the management of inflammation. � 2023 Newlands Press.Item Role of caveolin-eNOS platform and mitochondrial ATP-sensitive potassium channel in abrogated cardioprotective effect of ischemic preconditioning in postmenopausal women(Faculdade de Ciencias Farmaceuticas (Biblioteca), 2022-12-16T00:00:00) Goyal, Ahsas; Agrawal, Neetu; Jain, Ankit; Gupta, Jeetendra Kumar; Garabadu, DebapriyaCaveolin, the protein of the caveolar membrane, interacts and binds with endothelial nitric oxide synthase (eNOS), forming a caveolin-eNOS complex leading to suppression of the eNOS activity. Caveolin, therefore, maintains eNOS in the inactivated state leading to reduced nitric oxide (NO) production. Ischemic preconditioning disrupts the caveolin-eNOS complex leading to activation of the eNOS and thus results in cardioprotection. During ischemic preconditioning, NO produces cardioprotection by the opening of the KATP channel, and the caveolin forms a suitable signalling platform facilitating the interaction of NO with the KATP channel. Estrogen deficiency has been reported to upregulate caveolin-1 expression. The article aims to review the various mechanisms that placed the women at the risk of coronary artery diseases after postmenopausal estrogen deficiency and their role in the cardioprotective effect of ischemic preconditioning. � 2022, Faculdade de Ciencias Farmaceuticas (Biblioteca). All rights reserved.Item A Comprehensive Review on Preclinical Evidence-based Neuroprotective Potential of Bacopa monnieri against Parkinson's Disease(Bentham Science Publishers, 2022-03-17T00:00:00) Goyal, Ahsas; Gopika, Sainu; Kumar, Abhishek; Garabadu, DebapriyaParkinson's disease is a chronic and gradually progressive neurodegenerative disorder trig-gered due to the loss of dopamine-releasing neurons in the region of substantia nigra pars compacta characterized by the motor symptoms, such as tremor, bradykinesia, akinesia, and postural instability. Proteinopathies, mitochondrial dysfunction induced dopaminergic neuronal deterioration, and gene mutations are the hallmarks of Parkinson's disease. The bioactive components of Brahmi, such as Bacoside A, Bacoside B, and Bacosaponins, belong to various chemical families. Brahmi's neuropro-tective role includes reducing neuronal oxidative stress, dopaminergic neuronal degeneration, mito-chondrial dysfunction, inflammation, inhibition of ?-synuclein aggregation, and improvement of cognitive and learning behaviour. Researchers found that Bacopa monnieri significantly increased brain levels of glutathione, vitamin C, vitamin E, and vitamin A in rats exposed to cigarette smoke. Brahmi has a potent antioxidant property and neuroprotective effects against PD that help reduce oxidative stress and neuroinflammation and enhance dopamine levels. The review collates all the preclinical studies that prove the beneficial neuroprotective effect of Brahmi for treating PD. � 2022 Bentham Science Publishers.Item Mitochondria-targeted drug delivery systems for the effective treatment of neurodegenerative disorders(Elsevier, 2022-03-18T00:00:00) Khare, Vaishali; Gupta, Surbhi; Bisht, Preeti; Garabadu, DebapriyaMitochondria are known to be the powerhouse of the cell. Its dysfunction leads to several alterations in cellular physiology. Mitochondrial dysfunction is a well-documented process in the pathophysiology of neurodegeneration and neurodegenerative disorders. The interplay between mitochondrial dysfunction and oxidative stress is well suggested in the pathophysiology of neurodegenerative disorders. The activation of autophagy is also well established along with the mitochondrial impairment in neurodegenerative disorders. The relationship between mitochondrial dysfunction and excitotoxicity is also well established in the pathophysiology of neurodegenerative disorders. Enhanced apoptosis and necrosis is well established along with mitochondrial dysfunction in the pathophysiology of neurodegenerative disorders. Several synthetic and herbal drugs have been established in the management of mitochondrial dysfunction-induced neurodegenerative disorders. Little information is available about the formulations of the established mitochondria-targeted drugs in the management of neurodegenerative disorders. Therefore, critical attention is required in the development of mitochondria-targeted drug delivery systems for therapeutic and diagnostic applications in neurodegenerative disorders. � 2022 Elsevier Inc. All rights reserved.Item Quercetin Exhibits ?7nAChR/Nrf2/HO-1-Mediated Neuroprotection Against STZ-Induced Mitochondrial Toxicity and Cognitive Impairments in Experimental Rodents(Springer, 2021-09-23T00:00:00) Singh, Niraj Kumar; Garabadu, DebapriyaThe objective of the present study was to investigate the ?7nAChR-mediated Nrf2-dependant protective activity against streptozotocin (STZ)-induced brain mitochondrial toxicity in Alzheimer�s disease (AD)-like rats. STZ (3�mg/kg) was injected through an intracerebroventricular route to induce AD-like dementia. Repeated Quercetin (50�mg/kg, i.p.) administration attenuated cognitive impairments in the STZ-challenged animals during Morris water-maze and Y-maze tests. Quercetin significantly mitigated the STZ-induced increase in cholinergic dysfunction, such as the increase in acetylcholinesterase activity, decrease in acetylcholine level, and activity of choline acetyltransferase, and increase in amyloid-beta aggregation and mitochondrial toxicity in respect of mitochondrial bioenergetics, integrity, and oxidative stress in memory-challenged rat hippocampus, prefrontal cortex and, amygdala. Further, Quercetin significantly attenuated STZ-induced reduction in the ?7nAChRs and HO-1 expression levels in the selected rat brain regions. On the contrary, trigonelline (10�mg/kg, i.p.) and methyllycaconitine (2�mg/kg; i.p.) abolished the neuroprotective effects of Quercetin against STZ-induced behavioral, molecular, and biochemical alterations in the AD-like animals. Hence, Quercetin exhibits ?7nAChR/Nrf2/HO-1-mediated neuroprotection against STZ-challenged AD-like animals. Thus, Quercetin could be considered as a potential therapeutic option in the management of AD. Graphical Abstract: [Figure not available: see fulltext.] � 2021, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.Item Various Cellular and Molecular Axis Involved in the Pathogenesis of Asthma(Springer Nature, 2021-07-02T00:00:00) Bhatti, Gurjit Kaur; Khurana, Amit; Garabadu, Debapriya; Gupta, Prashant; Jawalekar, Snehal Sainath; Bhatti, Jasvinder Singh; Navik, UmashankerAsthma is a chronic inflammatory disease described by impaired lung function, airway hyperresponsiveness, episodic wheezing, and dyspnea. Asthma prevalence has risen drastically, and it is estimated that more than 339 million individuals worldwide had asthma with marked heterogeneity in pathophysiology and etiology. Several factors involved in the progression and development of asthma include allergens, pollutants, obesity, viruses, antigens, and many more, eliciting strong inflammatory and immune responses, causing airflow obstruction, and tightening of respiratory smooth muscle causing the characteristic asthma symptoms. Multiple complex molecular pathways are involved in asthma pathophysiologies such as immunoglobulin E, cytokines, nitric oxide, dendritic cells, leukotrienes, oxidative stress, and inflammatory infiltrate of mast cells, neutrophils, eosinophils, lymphocytes, innate immunity, and many more. The current chapter focuses on illustrating the various molecular pathways that contribute to asthma development and its progression. � The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021.Item Antinociceptive activity of standardized extract of Bacopa monnieri in different pain models of zebrafish(Elsevier Ireland Ltd, 2021-08-19T00:00:00) Sharma, Mahima; Gupta, Pankaj Kumar; Gupta, Pankaj; Garabadu, DebapriyaEthnopharmacological relevance: Bacopa monnieri L. (Scrophulariaceae) is commonly known as Brahmi and traditionally used as a neuroprotective herbal medicine. Recently, Bacopa monnieri exhibited significant therapeutic activity against animal model of neuropathic pain. However, the therapeutic potential of methanolic extract of Bacopa monnieri in experimental animal model is yet to establish. Aim of the study: The present study was designed to evaluate the anti-nociceptive potential of standardized methanolic extract of Bacopa monnieri in experimental adult zebrafish (Danio rerio) model of pain. Materials and methods: The methanolic extract of Bacopa monnieri (BME) was standardized to bacoside-A using chromatographic method. Subsequently, BME (0.75, 1.25 and 5.0 mg/ml) was evaluated for anti-nociceptive activity using adult zebrafish model. Results: Standardized BME showed antioxidant effect through radical quenching activity in in vitro study. BME at 1.25 mg/ml significantly decreased the nociceptive effect induced by different noxious agents like acetic acid where as BME at 2.5 mg/ml exhibited significant antinociceptive activity against glutamate, formalin, capsaicin, cinnamaldehyde when compared to control and sham group animals. Conclusion: BME exerted antinociceptive activity in adult zebrafish. It could be presumed that BME may involve glutamatergic receptor, ASIC and TRP channel activity in its anti-nociceptive effect. BME could be considered as a potential therapeutic option in the management of pain. � 2021 Elsevier B.V.