Biodiversity as a source of new pharmacophores: A new theory of memory III

2005 ◽  
Vol 77 (1) ◽  
pp. 75-81 ◽  
Author(s):  
◽  
M. Iqbal Choudhary
Keyword(s):  
Natural Products ◽  
Anticancer Agents ◽  
Neurological Disorders ◽  
In Vitro Bioassay ◽  
Natural Sources ◽  
Chemical Basis ◽  
Antioxidant Agents ◽  
A Cell ◽  
The Brain

Several classes of natural products with significant inhibitory activity against target enzymes involved in several diseases have been identified. Spectrophotometer and high-throughput assays were used to assess the inhibition of prolyl endopeptidase (PEP), which led us to some novel inhibitors having potential as anticancer agents. Inhibition of cholinesterase enzymes has led to the discovery of new inhibitors with potential for use in Alzheimer’s disease and other neurological disorders. We have also discovered several potent antioxidant agents from natural sources by using a battery of antioxidant assays. Anti-inflammatory activity of a number of natural products was assayed through a cell-based in vitro bioassay. This article also contains a section on a slightly different topic of chemical basis of memory as presented during the lecture. The theory of the chemical basis of memory based on hydrogen bonding in the brain is further elaborated.

scholarly journals Ingredients for Functional Drinks in Neurodegenerative Diseases: A Review

2009 ◽  
Vol 4 (5) ◽  
pp. 1934578X0900400
Author(s):  
Pilar Zafrilla ◽  
Juana M Morulas ◽  
José M. Rubio-Perez ◽  
Emma Cantos Villar
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Clinical Evidence ◽  
The Body ◽  
Neuroprotective Effects ◽  
Antioxidant Agents ◽  
Rate Of Progression ◽  
The Brain

Several studies have indicated that oxidative stress is a major risk factor for the initiation and progression of neurological disorders like Parkinson's disease (PD) and Alzheimer's (AD). Therefore, reducing oxidative stress appears to be a rational choice for the prevention and reduction in the rate of progression of these neurological disorders. The brain utilizes about 25% of respired oxygen even though it represents only 5% of the body weight. Free radicals are generated during the normal intake of oxygen, during infection, and during normal oxidative metabolism of certain substrates. Although experimental data are consistent in demonstrating the neuroprotective effects of antioxidants in vitro and in animal models, the clinical evidence that antioxidant agents may prevent or slow the course of these diseases is still relatively unsatisfactory, and insufficient to strongly modify clinical practice. In this paper, natural possible substances that could be added to a beverage to prevent or decrease the developing of neurodegenerative diseases are reviewed.

scholarly journals Anti-aggregation Effects of Phenolic Compounds on α-synuclein

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2444
Author(s):  
Kenjiro Ono ◽  
Mayumi Tsuji ◽  
Tritia R. Yamasaki ◽  
Giulio M. Pasinetti
Keyword(s):  
Phenolic Compounds ◽  
Gut Microbiota ◽  
Lewy Bodies ◽  
Hydroxybenzoic Acid ◽  
Dietary Polyphenols ◽  
Pathologic Features ◽  
Hydroxyphenylacetic Acid ◽  
A Cell ◽  
The Brain

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson’s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the efficacy of dietary polyphenol metabolism. Our recent studies on the brain-penetrating polyphenolic acids 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-hydroxyphenylacetic acid (3-HPPA), which are derived from gut microbiota-based metabolism of dietary polyphenols, demonstrated an in vitro ability to inhibit αS oligomerization and mediate aggregated αS-induced neurotoxicity. Additionally, 3-HPPA, 3,4-diHBA, 3-HBA, and 4-hydroxybenzoic acid significantly attenuated intracellular αS seeding aggregation in a cell-based system. This review focuses on recent research developments regarding neuroprotective properties, especially anti-αS aggregation effects, of phenolic compounds and their metabolites by the gut microbiome, including our findings in the pathogenesis of α-synucleinopathies.

Plant derived secondary metabolites in cancer therapy: actions, applications, and future prospective of dietaryflavonol (quercetin)

2019 ◽  
Vol 1 (6) ◽  
pp. 135-143
Author(s):  
Krishnagowdu Saravanan ◽  
Jayachandran Halka ◽  
Kumaresan Kowsalya ◽  
Muthukrishnan Arun
Keyword(s):  
Cancer Therapy ◽  
Secondary Metabolites ◽  
Anticancer Agents ◽  
Higher Plants ◽  
Lung Tumor ◽  
Chemical Constituents ◽  
Food Additives ◽  
Antioxidant Agents

Higher plants are prominent sources for several bioactive chemical constituents (secondary metabolites) who include photochemical, flavoring agents, fragrant molecules, and food additives. According to WHO estimates, it has been reported that more than 80% of population in developing countries prefer these natural bioactive active compounds for their primary health requirement. At present, conventional chemotherapy is constrained due to the nonselective toxicity to human organs and their usage is limited now a days. In a recent survey, more than 60% of cancer patients have been preferring adjuvant phototherapy along with chemotherapy. Thus, photochemical are being widely used as anticancer agents to target specific pathological pathways underlying cancer with low toxic profiles and side effects. These photochemical are cost-effective and easily accessible to the public to treat cancer diseases. These bioactive photochemical are meticulously belongs to secondary metabolites such as alkaloids, flavonoids, polyphenols.Among them, the flavonoids are polyphenolic substances, which are found in all parts of the plant such as flowers, fruits, leaves, roots, seeds, and bark. They possess high medicinal properties like being anti-cancer, anti-hypertensive, anti-inflammatory, anti-obesity, anti-malarial, antioxidant agents. Quercetin is major flavones associated with a profound antioxidant and medicinal property to prevent the oxidation of lipids in vitro and in vivo, and also exhibits direct proapoptotic effects on tumor cells. This compound has proven efficacy in targeting several cancer cells of breast, colon, prostate, ovarian, and lung tumor in vitro. The present review focuses on the effect of quercetin in cancer therapy.

scholarly journals Anticancer Agents from Diverse Natural Sources

2014 ◽  
Vol 9 (11) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Jabeena Khazir ◽  
Darren L. Riley ◽  
Lynne A. Pilcher ◽  
Pieter De-Maayer ◽  
Bilal Ahmad Mir
Keyword(s):  
Clinical Trials ◽  
Natural Products ◽  
Anticancer Agents ◽  
Marine Organisms ◽  
New Drugs ◽  
Human Diseases ◽  
Cancer Drugs ◽  
Natural Sources ◽  
Anti Cancer ◽  
Ancient Times

This review attempts to portray the discovery and development of anticancer agents/drugs from diverse natural sources. Natural molecules from these natural sources including plants, microbes and marine organisms have been the basis of treatment of human diseases since the ancient times. Compounds derived from nature have been important sources of new drugs and also serve as templates for synthetic modification. Many successful anti-cancer drugs currently in use are naturally derived or their analogues and many more are under clinical trials. This review aims to highlight the invaluable role that natural products have played, and continue to play, in the discovery of anticancer agents.

scholarly journals A cell-autonomous requirement for neutral sphingomyelinase 2 in bone mineralization

2011 ◽  
Vol 194 (2) ◽  
pp. 277-289 ◽  
Author(s):  
Zohreh Khavandgar ◽  
Christophe Poirier ◽  
Christopher J. Clarke ◽  
Jingjing Li ◽  
Nicholas Wang ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Skeletal Development ◽  
Specific Expression ◽  
Neutral Sphingomyelinase ◽  
Phosphodiesterase 3 ◽  
A Cell ◽  
Endocrine Factors ◽  
The Brain ◽  
Bone Abnormalities

A deletion mutation called fro (fragilitas ossium) in the murine Smpd3 (sphingomyelin phosphodiesterase 3) gene leads to a severe skeletal dysplasia. Smpd3 encodes a neutral sphingomyelinase (nSMase2), which cleaves sphingomyelin to generate bioactive lipid metabolites. We examined endochondral ossification in embryonic day 15.5 fro/fro mouse embryos and observed impaired apoptosis of hypertrophic chondrocytes and severely undermineralized cortical bones in the developing skeleton. In a recent study, it was suggested that nSMase2 activity in the brain regulates skeletal development through endocrine factors. However, we detected Smpd3 expression in both embryonic and postnatal skeletal tissues in wild-type mice. To investigate whether nSMase2 plays a cell-autonomous role in these tissues, we examined the in vitro mineralization properties of fro/fro osteoblast cultures. fro/fro cultures mineralized less than the control osteoblast cultures. We next generated fro/fro;Col1a1-Smpd3 mice, in which osteoblast-specific expression of Smpd3 corrected the bone abnormalities observed in fro/fro embryos without affecting the cartilage phenotype. Our data suggest tissue-specific roles for nSMase2 in skeletal tissues.

scholarly journals Adhesion, Invasion, and Translocation Characteristics of Listeria monocytogenes Serotypes in Caco-2 Cell and Mouse Models

2003 ◽  
Vol 69 (6) ◽  
pp. 3640-3645 ◽  
Author(s):  
Ziad W. Jaradat ◽  
Arun K. Bhunia
Keyword(s):  
Listeria Monocytogenes ◽  
Mouse Model ◽  
Cell Line ◽  
Mouse Bioassay ◽  
Adhesion Properties ◽  
Culture Model ◽  
A Cell ◽  
In Vitro Adhesion ◽  
The Brain

ABSTRACT Adhesion is a crucial first step in Listeria monocytogenes pathogenesis. In this study, we examined how the adhesion properties of serotypes correlate with their invasion efficiencies in a cell culture model (Caco-2) and in a mouse model. Adhesion characteristics of all 13 serotypes of L. monocytogenes (25 strains) were analyzed, which yielded three distinct groups (P < 0.05) with high-, medium-, and low-level-adhesion profiles. The efficiency of these strains in invading the Caco-2 cell line was analyzed, which produced two groups; however, the overall correlation (R 2) was only 0.1236. In the mouse bioassay, all selected strains, irrespective of their adhesion profiles, translocated to the liver and the spleen with almost equal frequencies that did not show any clear relationship with adhesion profiles. However, the serotypes with increased adhesion showed a slightly increased translocation to the brain (R 2 = 0.3371). Collectively, these results indicate that an in vitro adhesion profile might not be an accurate assessment of a strain's ability to invade a cultured cell line or organs or tissues in a mouse model.

Biodiversity: A wonderful source of exciting new pharmacophores. Further to a new theory of memory

2002 ◽  
Vol 74 (4) ◽  
pp. 511-517 ◽  
Author(s):  
◽  
M. Iqbal Choudhary
Keyword(s):  
Natural Products ◽  
Hydrogen Bonding ◽  
Chemical Compounds ◽  
Marine Organisms ◽  
Chemical Diversity ◽  
Chemical Basis ◽  
Biological Resources ◽  
Bioactive Natural Products ◽  
New Class ◽  
The Brain

The diverse biological resources in nature are vast factories of chemical diversity. With the recent advances in the biological and chemical sciences it is now easier than ever to explore the potential uses of immense biological resources in a sustainable manner. Our investigations focused on the bioprospecting of both terrestrial and marine organisms have led to the discovery of a number of interesting chemical compounds. The discovery of a new class of cholinesterase, α-glucosidase and phosphodiesterase I inhibitors, several new antioxidants, and other classes of bioactive natural products is presented. The theory of the chemical basis of memory through hydrogen bonding in the brain is further elaborated.

scholarly journals IL-22 hinders antiviral T cell responses and exacerbates neurological disorders in ZIKV-infected immunocompetent neonatal mice

2020 ◽  
Author(s):  
Yuejin Liang ◽  
Panpan Yi ◽  
Wenjuan Ru ◽  
Zuliang Jie ◽  
Hui Wang ◽  
...  
Keyword(s):  
Weight Loss ◽  
T Cell ◽  
Neurological Disorders ◽  
T Cell Responses ◽  
Host Immunity ◽  
Zikv Infection ◽  
Cell Responses ◽  
The Brain

Abstract Background The Zika virus (ZIKV) outbreak that occurred in multiple countries was linked to increased risk of neurological disorders and congenital defects. However, host immunity and immune-mediated pathogenesis in ZIKV infection are not well understood. Interleukin-22 (IL-22) is a crucial cytokine for regulating host immunity in infectious diseases. Whether IL-22 plays a role in ZIKV infection is unknown. Methods The cellular source of IL-22 was identified in IFNAR−/− mice and WT neonatal mice during ZIKV infection. To determine the role of IL-22, we challenged 1-day-old wild-type (WT) and IL-22−/− mice with ZIKV and monitored clinical manifestations. Glial cell activation in the brain was assessed by confocal imaging. ZIKV-specific CD8+ T cell responses in both the spleen and brain were analyzed by flow cytometry. In addition, we infected mouse primary astrocytes in vitro, and characterized the reactive astrocyte phenotype. Human glial cell line was also infected with ZIKV in the presence of IL-22, followed by the evaluation of cell proliferation, cytokine expression and viral loads. Results We found that γδ T cells were the main source of IL-22 during ZIKV infection in both the spleen and brain. WT mice began to develop weight loss, staggered steps, bilateral hind limb paralysis, weakness at 10 days post-infection (dpi), and ultimately succumbed to infection at 16–19 dpi. Surprisingly, IL-22 deficiency lessened weight loss, moderated the systemic inflammatory response, and greatly reduced the incidence of neurological disorders and mortality. ZIKV infection facilitated a neurotoxic polarization of A1-prone astrocytes in vitro. Additional analysis demonstrated that the absence of IL-22 resulted in reduced activation of microglia and astrocytes in the cortex. Although IL-22 displayed a marginal effect on glial cells in vitro, IL-22−/− mice mounted more vigorous ZIKV-specific CD8+ T cell responses, which led to a more effective control of ZIKV in the brain. Conclusions Our data revealed a pathogenic role of IL-22 in ZIKV encephalitis.

scholarly journals Topologically controlled circuits of human iPSC-derived neurons for electrophysiology recordings

2021 ◽  
Author(s):  
Sophie Girardin ◽  
Blandine Clément ◽  
Stephan J. Ihle ◽  
Sean Weaver ◽  
Jana B. Petr ◽  
...  
Keyword(s):  
Information Processing ◽  
Neurological Disorders ◽  
Induced Pluripotent Stem Cell ◽  
Animal Origin ◽  
Great Promise ◽  
Human Neurons ◽  
Induced Pluripotent ◽  
Human Ipsc ◽  
The Brain

Bottom-up neuroscience, which consists of building and studying controlled networks of neurons in vitro, is a promising method to investigate information processing at the neuronal level. However, in vitro studies tend to use cells of animal origin rather than human neurons, leading to conclusions that might not be generalizable to humans and limiting the possibilities for relevant studies on neurological disorders. Here we present a method to build arrays of topologically controlled circuits of human induced pluripotent stem cell (iPSC)-derived neurons. The circuits consist of 4 to 50 neurons with mostly unidirectional connections, confined by microfabricated polydimethylsiloxane (PDMS) membranes. Such circuits were characterized using optical imaging and microelectrode arrays (MEAs). Electrophysiology recordings were performed on circuits of human iPSC-derived neurons for at least 4.5 months. We believe that the capacity to build small and controlled circuits of human iPSC-derived neurons holds great promise to better understand the fundamental principles of information processing and storing in the brain.

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