School Of Health Sciences
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Item 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, RichmondBenzoxazepines 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.Item Ferulic acid ameliorates neurodegeneration via the Nrf2/ARE signalling pathway: A Review(Elsevier B.V., 2022-10-30T00:00:00) Singh, Surbhi; Arthur, Richmond; Upadhayay, Shubham; Kumar, PuneetBackground: Ferulic acid is a polyphenolic phytoconstituent synthesized from the metabolism of amino acids phenylalanine and tyrosine found in fruits and vegetables. Neurodegenerative disorders have been a thorn in the flesh of neuroscientists owing in part to the increase in the aged population. Several drugs used in the management of these disorders are either ineffective or come with unbearable side effects. We present a review of ferulic acid focusing on leveraging its antioxidant property in an attempt to explain its role in neurodegenerative disorders. Basic procedure: data were obtained by perusing scientific databases including Web of Science and PubMed. It was realised that 18,000 articles were associated with ferulic acid from 1960-to 2022. We narrowed it down using the keywords neuroprotection, and antioxidant of which we had 239 articles. Main findings: results indicated that ferulic acid has wide neuropharmacological applications due to its antioxidant, anti-inflammatory, neuroprotective and antiapoptotic effects among others. The neuroprotective effect of ferulic acid has been studied in many diseases like Alzheimer's, Epilepsy, and Parkinson's disease. Principal conclusion: the neuroprotective potential of FA may be due to its ability to absorb active forms of oxygen and nitrogen and use redox-bearing compounds to regulate genetic expression including, encoding for antioxidant enzymes, the anti-apoptotic protein family Bcl-2, and pro-survival neurotrophic factors like BDNF. Its higher bioavailability and lipophilic nature make it a better drug candidate than other polyphenols for neurological disorders. � 2022 The Author(s)Item Berberine Ameliorate Haloperidol and 3-Nitropropionic Acid-Induced Neurotoxicity in Rats(Springer, 2022-07-25T00:00:00) Kadir, Abdul; Singh, Jasdeep; Rahi, Vikrant; Kumar, PuneetBerberine 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.Item Can bilirubin nanomedicine become a hope for the management of COVID-19?(Churchill Livingstone, 2021-02-15T00:00:00) Khurana, Isha; Allawadhi, Prince; Khurana, Amit; Srivastava, Amit Kumar; Navik, Umashanker; Banothu, Anil Kumar; Bharani, Kala KumarBilirubin has been proven to possess significant anti-inflammatory, antioxidant and antiviral activities. Recently, it has been postulated as a metabolic hormone. Further, moderately higher levels of bilirubin are positively associated with reduced risk of cardiovascular diseases, diabetes, metabolic syndrome and obesity. However, due to poor solubility the therapeutic delivery of bilirubin remains a challenge. Nanotechnology offers unique advantages which may be exploited for improved delivery of bilirubin to the target organ with reduced risk of systemic toxicity. Herein, we postulate the use of intravenous administration or inhalational delivery of bilirubin nanomedicine (BNM) to combat systemic dysfunctions associated with COVID-19, owing to the remarkable preclinical efficacy and optimistic results of various clinical studies of bilirubin in non-communicable disorders. BNM may be used to harness the proven preclinical pharmacological efficacy of bilirubin against COVID-19 related systemic complications. � 2021 Elsevier LtdItem Assessment and identification of bioactive metabolites from terrestrial Lyngbya spp. responsible for antioxidant, antifungal, and anticancer activities(Institute for Ionics, 2023-09-09T00:00:00) Verma, Shaloo; Suman, Prabhat; Mandal, Somnath; Kumar, Roshan; Sahana, Nandita; Siddiqui, Nahid; Chakdar, HillolLyngbya from fresh and marine water produces an array of pharmaceutically bioactive therapeutic compounds. However, Lyngbya from agricultural soil is still poorly investigated. Hence, in this study, the bioactive potential of different Lyngbya spp. extract was explored. Intracellular petroleum ether extract of L. hieronymusii K81 showed the highest phenolic content (626.22 � 0.65 ?g GAEs g?1 FW), while intracellular ethyl acetate extract of L. aestuarii K97 (74.02 � 0.002 mg QEs g?1 FW) showed highest flavonoid content. Highest free radical scavenging activity in terms of ABTS�+ was recorded in intracellular methanolic extract of Lyngbya sp. K5 (97.85 � 0.068%), followed by L. wollei K80 (97.22 � 0.059%) while highest DPPH� radical scavenging activity observed by intracellular acetone extract of Lyngbya sp. K5 (54.59 � 0.165%). All the extracts also showed variable degrees of antifungal activities against Fusarium udum, F. oxysporum ciceris, Colletotrichum capsici, and Rhizoctonia solani. Further, extract of L. wollei K80 and L. aestuarii K97 showed potential anticancer activities against MCF7 (breast cancer) cell lines. GC-MS analyses of intracellular methanolic extract of L. wollei K80 showed the dominance of PUFAs with 9,12,15-octadecatrienoic acid, methyl ester, (Z,Z,Z) as the most abundant bioactive compound. On the other hand, the extracellular ethyl acetate extract of L. aestuarii K97 was rich in alkanes and alkenes with 1-hexyl-2-nitrocyclohexane as the most predominant compound. Extracts of Lyngbya spp. rich in novel secondary metabolites such as PUFAs, alkanes, and alkenes can be further explored as an alternative and low-cost antioxidant and potential apoptogens for cancer therapy. � 2023, The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.Item TcI isolates of Trypanosoma cruzi exploit the antioxidant network for enhanced intracellular survival in macrophages and virulence in mice(American Society for Microbiology, 2016) Zago, M.P.; Hosakote, Y.M.; Koo, S.-J.; Dhiman, M.; Pi?eyro, M.D.; Parodi-Talice, A.; Basombrio, M.A.; Robello, C.; Gargc, N.J.Trypanosoma cruzi species is categorized into six discrete typing units (TcI to TcVI) of which TcI is most abundantly noted in the sylvatic transmission cycle and considered the major cause of human disease. In our study, the TcI strains Colombiana (COL), SylvioX10/4 (SYL), and a cultured clone (TCC) exhibited different biological behavior in a murine model, ranging from high parasitemia and symptomatic cardiomyopathy (SYL), mild parasitemia and high tissue tropism (COL), to no pathogenicity (TCC). Proteomic profiling of the insect (epimastigote) and infective (trypomastigote) forms by two-dimensional gel electrophoresis/ matrix-assisted laser desorption ionization-time of flight mass spectrometry, followed by functional annotation of the differential proteome data sets (?2-fold change, P<0.05), showed that several proteins involved in (i) cytoskeletal assembly and remodeling, essential for flagellar wave frequency and amplitude and forward motility of the parasite, and (ii) the parasite-specific antioxidant network were enhanced in COL and SYL (versus TCC) trypomastigotes. Western blotting confirmed the enhanced protein levels of cytosolic and mitochondrial tryparedoxin peroxidases and their substrate (tryparedoxin) and iron superoxide dismutase in COL and SYL (versus TCC) trypomastigotes. Further, COL and SYL (but not TCC) were resistant to exogenous treatment with stable oxidants (H2O2 and peroxynitrite [ONOO-]) and dampened the intracellular superoxide and nitric oxide response in macrophages, and thus these isolates escaped from macrophages. Our findings suggest that protein expression conducive to increase in motility and control of macrophage-derived free radicals provides survival and persistence benefits to TcI isolates of T. cruzi. ? 2016, American Society for Microbiology.Item Innate Immune Responses and Antioxidant/Oxidant Imbalance Are Major Determinants of Human Chagas Disease(Public Library of Science, 2013) Dhiman, Monisha; Coronado, Yun A.; Vallejo, Cecillia K.; Peterson, John R.; Ejilemele, Adetoun; Nunez, Sonia; Zago, Maria Paola; Spratt, Hiedi; Garg, Nisha JainBackground:We investigated the pathological and diagnostic role of selected markers of inflammation, oxidant/antioxidant status, and cellular injury in human Chagas disease.Methods:Seropositive/chagasic subjects characterized as clinically-symptomatic or clinically-asymptomatic (n = 116), seronegative/cardiac subjects (n = 102), and seronegative/healthy subjects (n = 45) were analyzed for peripheral blood biomarkers.Results:Seropositive/chagasic subjects exhibited an increase in sera or plasma levels of myeloperoxidase (MPO, 2.8-fold), advanced oxidation protein products (AOPP, 56%), nitrite (5.7-fold), lipid peroxides (LPO, 12-17-fold) and malondialdehyde (MDA, 4-6-fold); and a decline in superoxide dismutase (SOD, 52%) and glutathione (GSH, 75%) contents. Correlation analysis identified a significant (p<0.001) linear relationship between inflammatory markers (AOPP/nitrite: r = 0.877), inflammation and antioxidant/oxidant status (AOPP/glutathione peroxidase (GPX): r = 0.902, AOPP/GSH: r = 0.806, Nitrite/GPX: 0.773, Nitrite/LPO: 0.805, MDA/MPO: 0.718), and antioxidant/oxidant levels (GPX/MDA: r = 0.768) in chagasic subjects. Of these, MPO, LPO and nitrite biomarkers were highly specific and sensitive for distinguishing seropositive/chagasic subjects from seronegative/healthy controls (p<0.001, training and fitting AUC/ROC >0.95). The MPO (r = 0.664) and LPO (r = 0.841) levels were also correlated with clinical disease state in chagasic subjects (p<0.001). Seronegative/cardiac subjects exhibited up to 77% decline in SOD, 3-5-fold increase in LPO and glutamate pyruvate transaminase (GPT) levels, and statistically insignificant change in MPO, AOPP, MDA, GPX, GSH, and creatine kinase (CK) levels.Conclusions:The interlinked effects of innate immune responses and antioxidant/oxidant imbalance are major determinants of human Chagas disease. The MPO, LPO and nitrite are excellent biomarkers for diagnosing seropositive/chagasic subjects, and MPO and LPO levels have potential utility in identifying clinical severity of Chagas disease. ? 2013 Dhiman et al.