scholarly journals Curcumin, Gut Microbiota, and Neuroprotection

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2426 ◽  
Author(s):  
Di Meo ◽  
Margarucci ◽  
Galderisi ◽  
Crispi ◽  
Peluso
Keyword(s):  
Neurological Diseases ◽  
Aqueous Solubility ◽  
Brain Health ◽  
Active Metabolites ◽  
Pharmacological Activities ◽  
Naturally Occurring ◽  
The Central Nervous System ◽  
High Concentrations

Curcumin, a nontoxic, naturally occurring polyphenol, has been recently proposed for the management of neurodegenerative and neurological diseases. However, a discrepancy exists between the well-documented pharmacological activities that curcumin seems to possess in vivo and its poor aqueous solubility, bioavailability, and pharmacokinetic profiles that should limit any therapeutic effect. Thus, it is possible that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of curcumin are present after oral administration. Indeed, a new working hypothesis that could explain the neuroprotective role of curcumin despite its limited availability is that curcumin acts indirectly on the central nervous system by influencing the “microbiota–gut–brain axis”, a complex bidirectional system in which the microbiome and its composition represent a factor which preserves and determines brain “health”. Interestingly, curcumin and its metabolites might provide benefit by restoring dysbiosis of gut microbiome. Conversely, curcumin is subject to bacterial enzymatic modifications, forming pharmacologically more active metabolites than curcumin. These mutual interactions allow to keep proper individual physiologic functions and play a key role in neuroprotection.

scholarly journals Interaction between Gut Microbiota and Curcumin: A New Key of Understanding for the Health Effects of Curcumin

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2499 ◽  
Author(s):  
Beatrice Scazzocchio ◽  
Luisa Minghetti ◽  
Massimo D’Archivio
Keyword(s):  
Gut Microbiota ◽  
Neurological Diseases ◽  
Curcuma Longa ◽  
Pharmacological Activities ◽  
Systemic Bioavailability ◽  
Microbiome Profile ◽  
Regulatory Effects ◽  
High Concentrations

Curcumin, a lipophilic polyphenol contained in the rhizome of Curcuma longa (turmeric), has been used for centuries in traditional Asian medicine, and nowadays it is widely used in food as dietary spice worldwide. It has received considerable attention for its pharmacological activities, which appear to act primarily through anti-inflammatory and antioxidant mechanisms. For this reason, it has been proposed as a tool for the management of many diseases, among which are gastrointestinal and neurological diseases, diabetes, and several types of cancer. However, the pharmacology of curcumin remains to be elucidated; indeed, a discrepancy exists between the well-documented in vitro and in vivo activities of curcumin and its poor bioavailability and chemical instability that should limit any therapeutic effect. Recently, it has been hypothesized that curcumin could exert direct regulative effects primarily in the gastrointestinal tract, where high concentrations of this polyphenol have been detected after oral administration. Consequently, it might be hypothesized that curcumin directly exerts its regulatory effects on the gut microbiota, thus explaining the paradox between its low systemic bioavailability and its wide pharmacological activities. It is well known that the microbiota has several important roles in human physiology, and its composition can be influenced by a multitude of environmental and lifestyle factors. Accordingly, any perturbations in gut microbiome profile or dysbiosis can have a key role in human disease progression. Interestingly, curcumin and its metabolites have been shown to influence the microbiota. It is worth noting that from the interaction between curcumin and microbiota two different phenomena arise: the regulation of intestinal microflora by curcumin and the biotransformation of curcumin by gut microbiota, both of them potentially crucial for curcumin activity. This review summarizes the most recent studies on this topic, highlighting the strong connection between curcumin and gut microbiota, with the final aim of adding new insight into the potential mechanisms by which curcumin exerts its effects.

scholarly journals New Evidence on the Role of D-Aspartate Metabolism in Regulating Brain and Endocrine System Physiology: From Preclinical Observations to Clinical Applications

2020 ◽  
Vol 21 (22) ◽  
pp. 8718
Author(s):  
Alessandro Usiello ◽  
Maria Maddalena Di Fiore ◽  
Arianna De Rosa ◽  
Sara Falvo ◽  
Francesco Errico ◽  
...  
Keyword(s):  
Animal Studies ◽  
Endocrine System ◽  
Postnatal Life ◽  
Functional Development ◽  
The Central Nervous System ◽  
High Concentrations ◽  
System Physiology ◽  
Metabolizing Enzyme

The endogenous amino acids serine and aspartate occur at high concentrations in free D-form in mammalian organs, including the central nervous system and endocrine glands. D-serine (D-Ser) is largely localized in the forebrain structures throughout pre and postnatal life. Pharmacologically, D-Ser plays a functional role by acting as an endogenous coagonist at N-methyl-D-aspartate receptors (NMDARs). Less is known about the role of free D-aspartate (D-Asp) in mammals. Notably, D-Asp has a specific temporal pattern of occurrence. In fact, free D-Asp is abundant during prenatal life and decreases greatly after birth in concomitance with the postnatal onset of D-Asp oxidase expression, which is the only enzyme known to control endogenous levels of this molecule. Conversely, in the endocrine system, D-Asp concentrations enhance after birth during its functional development, thereby suggesting an involvement of the amino acid in the regulation of hormone biosynthesis. The substantial binding affinity for the NMDAR glutamate site has led us to investigate the in vivo implications of D-Asp on NMDAR-mediated responses. Herein we review the physiological function of free D-Asp and of its metabolizing enzyme in regulating the functions of the brain and of the neuroendocrine system based on recent genetic and pharmacological human and animal studies.

scholarly journals Investigating the Feasibility of Mefenamic Acid Nanosuspension for Pediatric Delivery: Preparation, Characterization, and Role of Excipients

Processes ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 574
Author(s):  
Nikhat Perween ◽  
Sultan Alshehri ◽  
T. S. Easwari ◽  
Vivek Verma ◽  
Md. Faiyazuddin ◽  
...  
Keyword(s):  
Particle Size ◽  
Mefenamic Acid ◽  
Hydroxypropyl Methylcellulose ◽  
Sodium Dodecyl ◽  
Aqueous Solubility ◽  
Oral Route ◽  
Precipitation Method ◽  
Antisolvent Precipitation

Molecules with poor aqueous solubility are difficult to formulate using conventional approaches and are associated with many formulation delivery issues. To overcome these obstacles, nanosuspension technology can be one of the promising approaches. Hence, in this study, the feasibility of mefenamic acid (MA) oral nanosuspension was investigated for pediatric delivery by studying the role of excipients and optimizing the techniques. Nanosuspensions of MA were prepared by adopting an antisolvent precipitation method, followed by ultrasonication with varying concentrations of polymers, surfactants, and microfluidics. The prepared nanosuspensions were evaluated for particle size, morphology, and rheological measures. Hydroxypropyl methylcellulose (HPMC) with varying concentrations and different stabilizers including Tween® 80 and sodium dodecyl sulfate (SLS) were used to restrain the particle size growth of the developed nanosuspension. The optimized nanosuspension formula was stable for more than 3 weeks and showed a reduced particle size of 510 nm with a polydispersity index of 0.329. It was observed that the type and ratio of polymer stabilizers were responsive on the particle contour and dimension and stability. We have developed a biologically compatible oral nanoformulation for a first-in-class drug beautifully designed for pediatric delivery that will be progressed toward further in vivo enabling studies. Finally, the nanosuspension could be considered a promising carrier for pediatric delivery of MA through the oral route with enhanced biological impact.

Partial purification of galactinol synthase from leaves of Cucurbita pepo

1982 ◽  
Vol 60 (7) ◽  
pp. 1054-1059 ◽  
Author(s):  
John A. Webb
Keyword(s):  
Cucurbita Pepo ◽  
Partial Purification ◽  
Galactinol Synthase ◽  
Inositol 1 ◽  
Mature Leaves ◽  
Galactosyl Transferase ◽  
Naturally Occurring ◽  
High Concentrations ◽  
Uridine Nucleotides

An enzyme synthesizing galactinol, UDP-D-galactose:myo-inositol-1-α-D-galactosyl transferase (galactinol synthase), has been isolated and partially purified from mature leaves of Cucurbita pepo. The enzyme showed optimal activity between pH 7.5 and 8.0 and required Mn2+ and the presence throughout isolation, storage, and assay of a sulfhydryl protectant (β-mercaptoethanol). EDTA was completely inhibitory. From a range of metal ions only Mg2+ partially replaced Mn2+, while Co2+, Zn2+, Cu2+, and Ni2+ were inhibitory. The uridine nucleotides and UDP-glucose were from 40 to 80% inhibitory and probably constitute part of the in vivo control system. High concentrations of galactose, melibiose, and xylose were partially inhibitory. The enzyme appeared highly specific for myo-inositol and showed no ability for galactosyl transfer to any other naturally occurring sugar or sugar alcohol. Some reactivity was obtained with the isomeric scyllo-inositol but the product was not identified. A range of other sugar nucleotides were unreactive.

scholarly journals Src Family Kinases in the Central Nervous System：Their Emerging Role in Pathophysiology of Migraine and Neuropathic Pain

2020 ◽  
Vol 18 ◽  
Author(s):  
Lingdi Nie ◽  
Wen-Rui Ye ◽  
Shangbin Chen ◽  
Domenico Chirchiglia ◽  
Minyan Wang
Keyword(s):  
Neuropathic Pain ◽  
Tyrosine Kinases ◽  
Neurological Diseases ◽  
Src Family Kinases ◽  
Signalling Pathways ◽  
Pain Mechanisms ◽  
Promising Therapeutic Target ◽  
The Central Nervous System ◽  
The Relationship

: Src family kinases (SFK) are a group of non-receptor tyrosine kinases which play a pivotal role in cellular responses and oncogenesis. Accumulating evidence suggest that SFK also act as a key component in signalling pathways of the central nervous system (CNS) in both physiological and pathological conditions. Despite the crucial role of SFK in signal transduction of the CNS, the relationship between SFK and molecules implicated in pain has been relatively unexplored. This article briefly reviews the recent advances uncovering the interplay of SFK with diverse membrane proteins and intracellular proteins in the CNS and the importance of SFK in the pathophysiology of migraine and neuropathic pain. Mechanisms underlying the role of SFK in these conditions and potential clinical applications of SFK inhibitors in neurological diseases are also summarised. We propose that SFK are the convergent point of signalling pathways in migraine and neuropathic pain and may constitute a promising therapeutic target for these diseases.

scholarly journals Insights Into the Role of CSF1R in the Central Nervous System and Neurological Disorders

2021 ◽  
Vol 13 ◽  
Author(s):  
Banglian Hu ◽  
Shengshun Duan ◽  
Ziwei Wang ◽  
Xin Li ◽  
Yuhang Zhou ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Colony Stimulating Factor ◽  
Loss Of Function ◽  
Axonal Spheroids ◽  
The Central Nervous System ◽  
Stimulating Factor

The colony-stimulating factor 1 receptor (CSF1R) is a key tyrosine kinase transmembrane receptor modulating microglial homeostasis, neurogenesis, and neuronal survival in the central nervous system (CNS). CSF1R, which can be proteolytically cleaved into a soluble ectodomain and an intracellular protein fragment, supports the survival of myeloid cells upon activation by two ligands, colony stimulating factor 1 and interleukin 34. CSF1R loss-of-function mutations are the major cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and its dysfunction has also been implicated in other neurodegenerative disorders including Alzheimer’s disease (AD). Here, we review the physiological functions of CSF1R in the CNS and its pathological effects in neurological disorders including ALSP, AD, frontotemporal dementia and multiple sclerosis. Understanding the pathophysiology of CSF1R is critical for developing targeted therapies for related neurological diseases.

scholarly journals A neuroprotective role for microglia in prion diseases

2016 ◽  
Vol 213 (6) ◽  
pp. 1047-1059 ◽  
Author(s):  
Caihong Zhu ◽  
Uli S. Herrmann ◽  
Jeppe Falsig ◽  
Irina Abakumova ◽  
Mario Nuvolone ◽  
...  
Keyword(s):  
Prion Diseases ◽  
Protective Role ◽  
Proteinase K ◽  
Immune Effector ◽  
Effector Cells ◽  
The Central Nervous System ◽  
Cultured Slices ◽  
Simplex Virus

Microglial activation is a hallmark of most neurodegenerative disorders, and is particularly conspicuous in prion diseases. However, the role of microglia, which function as both primary immune effector cells and professional phagocytes in the central nervous system, remains contentious in the context of neurodegeneration. Here, we evaluated the effect of microglial depletion/deficiency on prion pathogenesis. We found that ganciclovir-mediated microglial ablation on tga20/CD11b-thymidine kinase of Herpes simplex virus (HSVTK) cerebellar organotypic cultured slices markedly aggravated prion-induced neurotoxicity. A similar deterioration of disease was recapitulated in in vivo microglial depletion in prion-infected tga20/CD11b-HSVTK mice. Additionally, deficiency of microglia in interleukin 34 knockout (IL34−/−) mice again resulted in significantly augmented proteinase K–resistant prion protein deposition and accelerated prion disease progression. These results provide unambiguous evidence for a general protective role of microglia in prion pathogenesis.

Ethnobotany, Pharmacological activities and Bioavailability studies of “King of Bitter” (Kalmegh): A Review (2010-2020)

2021 ◽  
Vol 24 ◽  
Author(s):  
Sharuti Mehta ◽  
Anil Kumar Sharma ◽  
Rajesh Kumar Singh
Keyword(s):  
Research Work ◽  
General Information ◽  
Future Research ◽  
Herbaceous Plant ◽  
Active Metabolites ◽  
Pharmacological Activities ◽  
Whole Plant ◽  
Pure Compounds

Background: Andrographis paniculata, commonly known as “Kalmegh”, is an annual herbaceous plant from family Acanthaceae. The whole plant of A. paniculata has explored for multiple pharmacological activities and is scientifically recognized by in-vivo and in-vitro studies. Various biotechnologically engineered techniques have been explored to enhance the bioavailability of this plant. Objective: In this review, we aim to present comprehensive recent advances in the ethnopharmacology, phytochemistry, specific pharmacology, safety and toxicology and bioavailability of A. paniculata and its pure compounds. Possible directions for future research are also outlined in brief, which will encourage advance investigations on this plant. Methods: Information on the recent updates of the present review is collected from different electronic scientific databases such as Science Direct, PubMed, Scopus, and Google Scholar. All the composed information is classified into different sections according to the objective of the paper. Results: More than hundred research and review papers have been studied and incorporated in the present manuscript. After vast literature search of A. paniculata, we present a noteworthy report of various phytoconstituents present in plant, which are accountable for potential therapeutic properties of the plant. Forty-five of studied articles give general information about introduction, ethnobotany and traditional uses of the plant. Twenty-two papers enclosed information about the phytoconstituents present in different parts of A. paniculata and seventy-two papers briefly outlined the pharmacological activities like antioxidant, anti-dengue, anti-ulcerogenic, antifungal, some miscellaneous activities like activity against SARS-CoV-2, antidiarrhoeal. Nineteen studies highlighted the research work conducted by various researchers to increased bioavailability of A. paniculata and two studies reported the safety and toxicology of the plant. Conclusion: This review incorporated the scientifically validated research work encompassing the ethnobotanical description of the subjected plant, phytochemical profile, various pharmacological activities, and recent approaches to enhance the bioavailability of active metabolites.

scholarly journals Intranasal Borna Disease Virus (BoDV-1) Infection: Insights into Initial Steps and Potential Contagiosity

2019 ◽  
Vol 20 (6) ◽  
pp. 1318 ◽  
Author(s):  
Alexandra Kupke ◽  
Sabrina Becker ◽  
Konstantin Wewetzer ◽  
Barbara Ahlemeyer ◽  
Markus Eickmann ◽  
...  
Keyword(s):  
Viral Infections ◽  
Cell Types ◽  
Nerve Fibers ◽  
Olfactory Pathway ◽  
Adult Rats ◽  
The Central Nervous System ◽  
Receptor Neurons

Mammalian Bornavirus (BoDV-1) typically causes a fatal neurologic disorder in horses and sheep, and was recently shown to cause fatal encephalitis in humans with and without transplant reception. It has been suggested that BoDV-1 enters the central nervous system (CNS) via the olfactory pathway. However, (I) susceptible cell types that replicate the virus for successful spread, and (II) the role of olfactory ensheathing cells (OECs), remained unclear. To address this, we studied the intranasal infection of adult rats with BoDV-1 in vivo and in vitro, using olfactory mucosal (OM) cell cultures and the cultures of purified OECs. Strikingly, in vitro and in vivo, viral antigen and mRNA were present from four days post infection (dpi) onwards in the olfactory receptor neurons (ORNs), but also in all other cell types of the OM, and constantly in the OECs. In contrast, in vivo, BoDV-1 genomic RNA was only detectable in adult and juvenile ORNs, nerve fibers, and in OECs from 7 dpi on. In vitro, the rate of infection of OECs was significantly higher than that of the OM cells, pointing to a crucial role of OECs for infection via the olfactory pathway. Thus, this study provides important insights into the transmission of neurotropic viral infections with a zoonotic potential.

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