Pharmacology - Research Publications

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1,3-Oxazine as a Promising Scaffold for the Development of Biologically Active Lead Molecules
(John Wiley and Sons Inc, 2023-10-16T00:00:00) Gupta, Nidhi; Saini, Vipin; Basavarajaiah, S.M.; Dar, Mohammad Ovais; Das, Rina; Dahiya, Randhir Singh
Heterocyclic compounds form an important part of wide range of biologically active molecules. The heteroatom provides them specificity for various receptors. 1,3-oxazine has been considered as a privileged scaffold in many medicinal chemistry applications. Compounds having 1,3-oxazine moiety exhibit broad range of biological applications such as anticancer, antimicrobial, anti-inflammatory, antiplatelet, antitubercular and alpha-glucosidase inhibition activities. In this review, we consolidate the recent developments in the synthesis and biological activities of 1,3-oxazine containing compounds. Also, the structure activity relationship (SAR) studies of different derivatives exhibiting several biological activities are summarized. Database such as Science direct, Pubmed and Google scholar were searched using keywords �1,3-Oxazine�, �synthesis�, �derivatives�, and �biological activities�. The review would provide a lead for the development of competent candidates with 1,3-oxazine moiety having broad range of applications in the treatment of several human disorders. � 2023 Wiley-VCH GmbH.
Acute toxicity assessment of methanolic extract of Zingiber roseum (Roscoe.) rhizome in swiss albino mice
(Elsevier B.V., 2023-03-25T00:00:00) Amanat, Muhammed; Shahid Ud Daula, A.F.M.; Singh, Randhir
Introduction: The rhizomes of Zingiber roseum plant have been used in traditional medicine to treat several ailments. Regardless of worth, no research has accounted its toxicity potential. So, the study was designed to determine safety and toxicity potential of Zingiber roseum rhizomes (ZRR) in acute oral toxicity model in swiss albino mice. Methods: Acute oral toxicity was assessed as per the guidelines of �The Brazilian Agency of National Health Surveillance'. In an acute toxicity investigation, 300 mg/kg, 600 mg/kg, and 1200 mg/kg of ZRR extract was orally administered to mice. Thereafter, the animals were monitored for 14 days. To analyze any potential toxicity, general behavior of animals, clinical symptoms of poisoning, body weight, biochemical and hematological marker, and liver histology was carried out. Results: Oral dosing of 300, 600, and 1200 mg/kg of crude extract did not produce mortality or any adverse effect in the laboratory animals. The control and treatment groups of mice exhibited similar behavioral characteristics, neurological signs and total body weight during the treatment period of 14 days. The markers of liver damage i.e., ALT and AST, total serum protein, and albumin did not show any significant change between extract-treated and control mice. The extracts also significantly suppressed ALP activity as compared to control. Kidney function was assessed in mice by measuring creatinine and urea level and no change was observed in level of creatinine and urea in experimental animals. Moreover, no alterations were observed in hematological markers and lipid profile (triglyceride and total cholesterol level). In addition, the liver showed normal architecture and no significant adverse consequences on histopathology analysis. Discussion & conclusion: These outcomes propose that LD50 of rhizomes of Z. roseum is higher than 1200 mg/kg b.w. and might be possibly safe for consumption. � 2023 The Author(s)
Advances in therapeutic applications of silver nanoparticles
(Elsevier Ireland Ltd, 2023-06-01T00:00:00) Kaushal, Ashutosh; Khurana, Isha; Yadav, Poonam; Allawadhi, Prince; Banothu, Anil Kumar; Neeradi, Dinesh; Thalugula, Sunitha; Barani, Percy Jasmine; Naik, Ramavath Redya; Navik, Umashanker; Bharani, Kala Kumar; Khurana, Amit
Nanotechnology is one of the most appealing area for developing new applications in biotechnology and medicine. For decades, nanoparticles have been extensively studied for a variety of biomedical applications. Silver has evolved into a potent antibacterial agent that can be used in a variety of nanostructured materials of various shapes and sizes. Silver nanoparticles (AgNP) based antimicrobial compounds are employed in a wide range of applications, including medicinal uses, surface treatment and coatings, the chemical and food industries, and agricultural productivity. When designing formulations for specific applications, the size, shape, and surface area of AgNPs are all crucial structural aspects to consider. Different methods for producing AgNPs with varying sizes and forms that are less harmful have been devised. The anticancer, anti-inflammatory, antibacterial, antiviral, and anti-angiogenic properties of AgNPs have been addressed in this review, as well as their generation and processes. Herein, we have reviewed the advances in therapeutic applications of AgNPs, as well as their limitations and barriers for future applications. � 2023 Elsevier B.V.
Advancing Cancer Immunotherapy: The Potential of mRNA Vaccines As a Promising Therapeutic Approach
(John Wiley and Sons Inc, 2023-10-04T00:00:00) Goyal, Falak; Chattopadhyay, Anandini; Navik, Umashanker; Jain, Aklank; Reddy, P. Hemachandra; Bhatti, Gurjit Kaur; Bhatti, Jasvinder Singh
mRNA vaccines have long been recognized for their ability to induce robust immune responses. The discovery that mRNA vaccines may also contribute to antitumor immunity has made them a promising therapeutic approach against cancer. Recent advances in understanding of immune system are precious in developing therapeutic strategies that target pathways involved in tumor survival and progression, leading to the most reliable therapeutic strategies in cancer treatment history. Among all traditional cancer treatments, cancer immunotherapies are less toxic and more effective, even in advanced or recurrent stages of cancer. Recent advancements in genomics and machine learning algorithms give new insight into vaccine development. mRNA vaccines are designed to interfere with stimulator of interferon genes (STING) and tumor-infiltrating lymphocytes pathways, activating more CD8+ T-cells involved in destroying tumor cells and inhibiting tumor growth. A stronger immune response can be achieved by incorporating immunological adjuvants alongside mRNA. Nonformulated or vehicle-based mRNA vaccines, when combined with adjuvants, efficiently express tumor antigens through antigen-presenting cells and stimulate both innate and adaptive immune responses. Codelivery with additional immunotherapeutic agents, such as checkpoint inhibitors, further enhances the efficacy of mRNA vaccines. This article focuses on the current clinical approaches and challenges to consider when developing mRNA-based vaccine technology for cancer treatment. � 2023 Wiley-VCH GmbH.
Animal models of attention-deficit hyperactivity disorder (ADHD)
(John Wiley and Sons Inc, 2021-01-15T00:00:00) Rahi, Vikrant; Kumar, Puneet
Attention-deficit hyperactivity disorder (ADHD) is a heterogeneous neuropsychiatric disorder characterized by three primary symptoms hyperactivity, attention deficit, and impulsiveness, observed in both children and adults. In childhood, this disorder is more common in boys than in girls, and at least 75% will continue to suffer from the disorder until adulthood. Individuals with ADHD generally have poor academic, occupational, and social functioning resulting from developmentally inappropriate levels of hyperactivity and impulsivity, as well as impaired ability to maintain attention on motivationally relevant tasks. Very few drugs available in clinical practice altogether abolish the symptoms of ADHD, therefore, to find new drugs and target it is essential to understand the neuropathological, neurochemical, and genetic alterations that lead to the progression of ADHD. With this contrast, an animal study is the best approach because animal models provide relatively fast invasive manipulation, rigorous hypothesis testing, as well as it provides a better angle to understand the pathological mechanisms involved in disease progression. Moreover, animal models, especially for ADHD, serve with good predictive validity would allow the assessment and development of new therapeutic interventions, with this aim, the present review collect the various animal models on a single platform so that the research can select an appropriate model to pursue his study. � 2021 International Society for Developmental Neuroscience
Animal models of Huntington�s disease and their applicability to novel drug discovery and development
(Taylor and Francis Ltd., 2023-04-12T00:00:00) Upadhayay, Shubham; Jamwal, Sumit; Kumar, Puneet
Introduction: Huntington�s disease (HD) is a progressive neurodegenerative disorder caused by an expansion in the CAG trinucleotide repeat in huntingtin (Htt) gene. The discovery of the HD-causing gene prompted the creation of new HD animal models, proving that mutations in the HD gene are linked to either loss of function of the wild-type (un-mutated) gene or toxic gain in the function of a mutated gene. Areas Covered: Animal models of HD have led to an increased understanding of its pathogenesis and resulted in the discovery of new therapeutic targets/drugs. The focus of this review is on the selection and validation of animal models for HD drug discovery. Furthermore, several drugs tested using various models in the preclinical phase have been compiled to demonstrate the applicability of these HD animal models. Expert opinion: The applicability of animal models for HD drug discovery has been well demonstrated. Nevertheless, despite the enormous progression made to date, the development of drug therapy to completely alleviate disease progression has not been achieved. Most of the pre-clinically tested drugs have shown promising results in alleviating HD-associated neurodegeneration and motor and non-motor symptoms, but only a few of them thrived to produce satisfactory results in the clinical phase. This failure has raised concerns about the selection of HD animal models and species, and new strategies for selection are mandated. � 2023 Informa UK Limited, trading as Taylor & Francis Group.
Antifungal synergistic effects and anti-biofilm formation activities of some bioactive 2,3-dihydro-1,5-benzoxazepine derivatives
(Springer Science and Business Media Deutschland GmbH, 2022-12-26T00:00:00) Odame, Felix; Neglo, David; Sedohia, Daniel; Arthur, Richmond
Benzoxazepines constitute a significant class of organic compounds extensively described in the literature. Several derivatives with pharmacological properties have been produced due to the semi-rigid azepine scaffold, which allows for the addition of other heteroatoms. This study investigated the possible antifungal effect and antioxidant activity of 2,3-dihydro-1,5-benzoxazepines. The antifungal effect was investigated using the broth dilution assay, while the antioxidant property was determined using the ABTS and DPPH scavenging tests. The results indicated that the 2,3-dihydro-1,5-benzoxazepine derivatives had antifungal properties and could be working via its fungicidal and biofilm inhibitory properties. It was also realized that it had synergistic effects when administered concomitantly with standard antifungal drugs. The antioxidant effects were high with 2,2-dimethyl-4-[(E)-2-(4-methylphenyl)ethenyl]-2,3-dihydro-1,5-benzoxazepine (1) compared to the other derivatives. It could be concluded that 2,3-dihydro-1,5-benzoxazepines could possess fungicidal and possible antioxidant properties. And hence could serve as new drug leads in discovering novel drugs that could help manage fluconazole-resistant vulvovaginal candidiasis. � 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Antimicrobial and anti-viral effects of selenium nanoparticles and selenoprotein based strategies: COVID-19 and beyond
(Editions de Sante, 2023-06-08T00:00:00) Khurana, Amit; Allawadhi, Prince; Singh, Vishakha; Khurana, Isha; Yadav, Poonam; Sathua, Kshirod Bihari; Allwadhi, Sachin; Banothu, Anil Kumar; Navik, Umashanker; Bharani, Kala Kumar
Deficiency of selenium (Se) has been described in a significant number of COVID-19 patients having a higher incidence of mortality, which makes it a pertinent issue to be addressed clinically for effective management of the COVID-19 pandemic. Se nanoparticles (SeNPs) provide a unique option for managing the havoc caused by the COVID-19 pandemic. SeNPs possess promising anti-inflammatory and anti-fibrotic effects by virtue of their nuclear factor kappa-light-chain-stimulator of activated B cells (NF?B), mitogen-activated protein kinase (MAPKs), and transforming growth factor-beta (TGF-?) modulatory activity. In addition, SeNPs possess remarkable immunomodulatory effects, making them a suitable option for supplementation with a much lower risk of toxicity compared to their elemental counterpart. Further, SeNPs have been shown to curtail viral and microbial infections, thus, making it a novel means to halt viral growth. In addition, it can be administered in the form of aerosol spray, direct injection, or infused thin-film transdermal patches to reduce the spread of this highly contagious viral infection. Moreover, a considerable decrease in the expression of selenoprotein along with enhanced expression of IL-6 in COVID-19 suggests a potential association among selenoprotein expression and COVID-19. In this review, we highlight the unique antimicrobial and antiviral properties of SeNPs and the immunomodulatory potential of selenoproteins. We provide the rationale behind their potentially interesting properties and further exploration in the context of microbial and viral infections. Further, the importance of selenoproteins and their role in maintaining a successful immune response along with their association to Se status is summarized. � 2023 Elsevier B.V.
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, Debapriya
Ethnopharmacological 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.
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.
Apoptosis and Pharmacological Therapies for Targeting Thereof for Cancer Therapeutics
(MDPI, 2022-04-08T00:00:00) Singh, Vishakha; Khurana, Amit; Navik, Umashanker; Allawadhi, Prince; Bharani, Kala Kumar; Weiskirchen, Ralf
Apoptosis is an evolutionarily conserved sequential process of cell death to maintain a homeostatic balance between cell formation and cell death. It is a vital process for normal eukaryotic development as it contributes to the renewal of cells and tissues. Further, it plays a crucial role in the elimination of unnecessary cells through phagocytosis and prevents undesirable immune responses. Apoptosis is regulated by a complex signaling mechanism, which is driven by interactions among several protein families such as caspases, inhibitors of apoptosis proteins, B-cell lymphoma 2 (BCL-2) family proteins, and several other proteases such as perforins and granzyme. The signaling pathway consists of both pro-apoptotic and pro-survival members, which stabilize the selection of cellular survival or death. However, any aberration in this pathway can lead to abnormal cell proliferation, ultimately leading to the development of cancer, autoimmune disorders, etc. This review aims to elaborate on apoptotic signaling pathways and mechanisms, interacting members involved in signaling, and how apoptosis is associated with carcinogenesis, along with insights into targeting apoptosis for disease resolution. � 2022 by the authors.
Apoptosis in Alzheimer�s disease: insight into the signaling pathways and therapeutic avenues
(Springer, 2023-04-26T00:00:00) Kumari, Sneha; Dhapola, Rishika; Reddy, Dibbanti HariKrishna
Alzheimer�s disease (AD) is characterized by the accumulation of hyperphosphorylated tau and amyloid-? (A?) protein resulting in synaptic loss and apoptosis. A? and tau deposition trigger apoptotic pathways that result in neuronal death. Apoptosis is considered to be responsible for manifestations associated with AD under pathological conditions. It regulates via extrinsic and intrinsic pathways. It activates various proteins including Bcl-2 family proteins like Bax, Bad, Bid, Bcl-XS, Bcl-XL and caspases comprising of initiator, effector and inflammatory caspases carried out through a cascade of events that finally lead to cell disintegration. The apoptotic elements interact with trophic factors, signaling molecules including Ras-ERK, JNK, GSK-3?, BDNF/TrkB/CREB and PI3K/AKT/mTOR. Ras-ERK signaling is involved in the progression of cell cycle and apoptosis. JNK pathway is also upregulated in AD which results in decreased expression of anti-apoptotic proteins. JAK-STAT triggers caspase-3 mediated apoptosis leading to neurodegeneration. The imbalance between autophagy and apoptosis is regulated by PI3K/Akt/mTOR pathway. GSK-3? is involved in the stimulation of pro-apoptotic factors resulting in dysregulation of apoptosis. Drugs like filgrastim, epigallocatechin gallate, curcumin, nicergoline and minocycline are under development which target these pathways and modulate the disease condition. This study sheds light on apoptotic pathways that are cardinal for neuronal survival and perform crucial role in the occurrence of AD along with the trends in therapeutics targeting apoptosis induced AD. To develop prospective treatments for AD, it is desirable to elucidate potential targets including restoration apoptotic balance, regulation of caspases, Bcl-2 and other crucial proteins involved in apoptosis mediated AD. � 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Apoptotic Cell Death in Cardiomyocytes Induced by Hypoxia from Cobalt Chloride Is Hastened by SGLT-1 Inhibition
(Mary Ann Liebert Inc., 2023-09-19T00:00:00) Kanwal, Abhinav; Liu, Lu; Bansal, Puneet Kumar; Kumar, Hemant; Singh, Shailendra Pratap
Introduction: Myocardial ischemia is responsible for the deaths of millions of people every year. Cardiac hypoxia reduces the efficiency with which the heart muscle pumps blood. When one or more of the coronary arteries abruptly and severely narrows or closes off, this is known as an acute coronary syndrome (ACS). Ischemia of the heart muscle can also cause potentially fatal arrhythmias. More information about this topic is required. Methods: The effects of SGLT-1 inhibition were studied using a different disease model, the cobalt chloride (CoCl2) hypoxia paradigm. The MTT assay was used to examine the effects of CoCl2 with and without Phlorizin (PZ) on glucose uptake, caspase activity, and metabolic/cytotoxic activities in SGLT-1 overexpressed H9C2 cells. Both SGLT-1 siRNA silencing and PZ treatment of SGLT-1 overexpressed neonatal rat cardiomyocytes were studied. Results and Discussion: Using flow cytometry, we were able to distinguish between metabolically active (PI-stained) and inactive (annexin-stained) live cells, as well as apoptotic (annexin-stained) and necrotic (PI-stained) cells. Caspase 3, 9, bcl-2, HIF-1a, and SGLT-1 expression, as well as oxidative stress, were examined using Western blotting. H9C2 cells showed increased caspase 3 and 9 activity in the CoCl2 group compared to the control, and these increases were further amplified by PZ cotreatment. PZ did not counteract CoCl2's effects of decreased glucose absorption and MTT activity. Conclusion: PZ increased cardiomyocyte apoptosis and decreased metabolic quiescent cells. PZ had no effect on the oxidative stress and necrosis that CoCl2 caused. CoCl2-induced SGLT-1 reduction leads to rapid apoptotic cell death. � Copyright 2023, Mary Ann Liebert, Inc., publishers 2023.
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.
Bacillus Calmette-Gu�rin Vaccine Attenuates Haloperidol-Induced TD-like Behavioral and Neurochemical Alteration in Experimental Rats
(2023-11-20T00:00:00) Yedke, Narhari Gangaram; Upadhayay, Shubham; Singh, Randhir; Jamwal, Sumit; Ahmad, Sheikh F.; Kumar, Puneet
Tardive dyskinesia (TD) is a hyperkinetic movement disorder that displays unusual involuntary movement along with orofacial dysfunction. It is predominantly associated with the long-term use of antipsychotic medications, particularly typical or first-generation antipsychotic drugs such as haloperidol. Oxidative stress, mitochondrial dysfunction, neuroinflammation, and apoptosis are major pathophysiological mechanisms of TD. The BCG vaccine has been reported to suppress inflammation, oxidative stress, and apoptosis and exert neuroprotection via several mechanisms. Our study aimed to confirm the neuroprotective effect of the BCG vaccine against haloperidol-induced TD-like symptoms in rats. The rats were given haloperidol (1 mg/kg, i.p.) for 21 days after 1 h single administration of the BCG vaccine (2 � 107 cfu). Various behavioral parameters for orofacial dyskinesia and locomotor activity were assessed on the 14th and 21st days after haloperidol injection. On the 22nd day, all rats were euthanized, and the striatum was isolated to estimate the biochemical, apoptotic, inflammatory, and neurotransmitter levels. The administration of the BCG vaccine reversed orofacial dyskinesia and improved motor function in regard to haloperidol-induced TD-like symptoms in rats. The BCG vaccine also enhanced the levels of antioxidant enzymes (SOD, GSH) and reduced prooxidants (MDA, nitrite) and pro-apoptotic markers (Cas-3, Cas-6, Cas-9) in rat brains. Besides this, BCG treatment also restored the neurotransmitter (DA, NE, 5-HT) levels and decreased the levels of HVA in the striatum. The study findings suggest that the BCG vaccine has antioxidant, antiapoptotic, and neuromodulatory properties that could be relevant in the management of TD.
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.
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.
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, Rahul
Aim: 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.
Biomedical applications of polysaccharide nanoparticles for chronic inflammatory disorders: Focus on rheumatoid arthritis, diabetes and organ fibrosis
(Elsevier Ltd, 2021-11-22T00:00:00) Allawadhi, Prince; Singh, Vishakha; Govindaraj, Kannan; Khurana, Isha; Sarode, Lopmudra P.; Navik, Umashanker; Banothu, Anil Kumar; Weiskirchen, Ralf; Bharani, Kala Kumar; Khurana, Amit
Polysaccharides are biopolymers distinguished by their complex secondary structures executing various roles in microorganisms, plants, and animals. They are made up of long monomers of similar type or as a combination of other monomeric chains. Polysaccharides are considered superior as compared to other polymers due to their diversity in charge and size, biodegradability, abundance, bio-compatibility, and less toxicity. These natural polymers are widely used in designing of nanoparticles (NPs) which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. The side chain reactive groups of polysaccharides are advantageous for functionalization with nanoparticle-based conjugates or therapeutic agents such as small molecules, proteins, peptides and nucleic acids. Polysaccharide NPs show excellent pharmacokinetic and drug delivery properties, facilitate improved oral absorption, control the release of drugs, increases in vivo retention capability, targeted delivery, and exert synergistic effects. This review updates the usage of polysaccharides based NPs particularly cellulose, chitosan, hyaluronic acid, alginate, dextran, starch, cyclodextrins, pullulan, and their combinations with promising applications in diabetes, organ fibrosis and arthritis. � 2021 Elsevier Ltd
Blockade of protease-activated receptor 2 (PAR-2) attenuates vascular dyshomeostasis and liver dysfunction induced by dengue virus infection
(Churchill Livingstone, 2022-06-27T00:00:00) Sood, Ankita; Gautam, Isha; Singh, Gaaminepreet; Joshi, Jagdish Chandra; Dahiya, Randhir Singh; Arora, Sandeep
The World Health Organization (WHO) recognizes dengue infection as a major public health concern in tropical and subtropical countries. Dengue infection is recognized as the second most deadly vector-borne disease in the world, based upon its incidence and mortality rate. Vascular dyshomeostasis and liver dysfunction are the major pathological manifestations in dengue patients. Vascular events in dengue patients include dropping of pulse rate, increased capillary leakage, hypotension, life-threatening hemorrhage due to release of inflammatory cytokines, growth factors, matrix metalloproteinase (MMP). The evident increase in cytokines, chemokines, and growth factors could further induce the release of pro- inflammatory cytokines and reactive oxygen species (ROS) by activating macrophages, monocytes, and T cells resulting in endothelial dysfunction and enhanced permeability in vessels. Moreover, the anti-dengue viral protein antibodies could target clotting cascades and endothelial cells, contributing to the vascular complications. Evidence has also indicated that infiltration of NK T cells and cytotoxic CD8+ cells during the early and late phases of dengue infection results in intra-hepatic damage. Several pieces of evidence have revealed that PAR-2 activation could regulate inflammatory cytokine release, immune cell activation, and endothelial cell damage. Thus, PAR-2 activation can be associated with vascular dyshomeostasis and hepatic dysfunction during critical phases of dengue infection. In this study, we correlate the pathological manifestations of dengue infection with PAR-2 activation and generate the proof-of-concept that targeting this receptor could abrogate these changes. � 2022 Elsevier Ltd