Encapsulation of Opiorphin in Polymer-coated Alginate Beads for Controlled Delivery and Painkilling

Opiorphin (Oph) is a naturally produced endogenous peptide with a strong analgesic effect, superior to that of morphine, and without the severe side effects that morphine and morphine-like drugs exert. However, despite its strong therapeutic potential, the short duration of action, probably due to its low chemical stability and rapid degradation by the peptidases in the bloodstream, represents a serious obstacle to the Oph use into clinical practice. In this work a novel approach to construct Oph-loaded particles as a platform for its delivery has been developed. Gel beads loaded with Oph were synthesized from alginate, a naturally occurring biodegradable anionic polysaccharide, and coated with polyelectrolyte multilayers (from natural polyelectrolytes (chitosan and hyaluronic acid) and synthetic polyelectrolytes (poly(allylamine hydrochloride) and poly(styrene sulfonate)) or hybrid polyelectrolyte-graphene oxide multilayers. All coated Oph-loaded alginate beads show prolonged drug release compared to the non-coated ones, but the extent of the prolongation depends on the type of the coating. We expect that the successful encapsulation of opiorphin in biodegradable particles will provide an opportunity for the development of adequate drug delivery system with effective and prolonged analgesic activity and will offer a new alternative for pain management.

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A Dual Sensor for Biogenic Amines and Oxygen Based on Genipin Immobilized in Edible Calcium Alginate Gel Beads

10.26434/chemrxiv.12252323 ◽

2020 ◽

Author(s):

Ian Mallov ◽

Fiona Jeeva ◽

Chris Caputo

Keyword(s):

Biogenic Amines ◽

Calcium Alginate ◽

Alginate Beads ◽

Colorimetric Sensing ◽

Naturally Occurring ◽

Gel Beads ◽

Dual Sensor ◽

Calcium Alginate Gel ◽

Toxic Food

Food is often wasted due to real or perceived concerns about preservation and shelf life. Thus, precise, accurate and consumer-friendly methods of indicating whether food is safe for consumers are drawing great interest. The colorimetric sensing of biogenic amines released as food degrades is a potential way of determining the quality of the food. Herein, we report the use of genipin, a naturally occurring iridoid, as a dual colorimetric sensor for both oxygen and biogenic amines. Immobilization of genipin in edible calcium alginate beads demonstrates that it is a capable sensor for amine vapors and can be immobilized in a non-toxic, food-friendly matrix.

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A Dual Sensor for Biogenic Amines and Oxygen Based on Genipin Immobilized in Edible Calcium Alginate Gel Beads

10.26434/chemrxiv.12252323.v1 ◽

2020 ◽

Author(s):

Ian Mallov ◽

Fiona Jeeva ◽

Chris Caputo

Keyword(s):

Biogenic Amines ◽

Calcium Alginate ◽

Alginate Beads ◽

Colorimetric Sensing ◽

Naturally Occurring ◽

Gel Beads ◽

Dual Sensor ◽

Calcium Alginate Gel ◽

Toxic Food

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Nitrification and Autotrophic Denitrification in Calcium Alginate Beads

Water Science & Technology ◽

10.2166/wst.1987.0199 ◽

1987 ◽

Vol 19 (1-2) ◽

pp. 175-182 ◽

Cited By ~ 16

Author(s):

Z. Lewandowski ◽

R. Bakke ◽

W. G. Characklis

Keyword(s):

Calcium Carbonate ◽

Calcium Ions ◽

Continuous Flow ◽

Calcium Alginate ◽

Microbial Respiration ◽

Flow System ◽

Alginate Beads ◽

Alginate Gel ◽

Gel Beads ◽

Calcium Alginate Gel

Immobilization of nitrifiers and autotrophic denitrifiers (Thiobacillus denitrificans) within calcium alginate gel was demonstrated. Calcium carbonate reagent was immobilized along with bacteria as the stabilizing agent. Protons released as a result of microbial respiration reacted with calcium carbonate producing calcium ions which internally stabilized the calcium alginate gel. The microbially active gel beads were mechanically stable and active for three months in a continuous flow system without addition of calcium.

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β-1, 3-Glucan attenuated chronic unpredictable mild stress induced cognitive impairment in rodents via normalizing corticosterone levels

Central Nervous System Agents in Medicinal Chemistry ◽

10.2174/1871524920666200810142359 ◽

2020 ◽

Vol 20 ◽

Author(s):

Saniya Hashim Khan ◽

Sheraz Khan ◽

Inamullah Khan ◽

Narmeen Hashim

Keyword(s):

Water Maze ◽

Memory Impairment ◽

Glucocorticoid Receptors ◽

Therapeutic Potential ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Neuroprotective Effects ◽

Injurious Effect ◽

Naturally Occurring ◽

Dose Dependent

Background: Chronic stress elevates the cortisol beyond normal levels, which affects cognition including learning & memory. This injurious effect is primarily mediated via over excitation of metabotropic glucocorticoid receptors (mGR). Methods: The present study was aimed appraise the neuroprotective effects of naturally occurring molecule β-1,3-glucan by interfering with stress-cortisol-mGR axis. Our data of virtual screening (in silico) exhibited the promising interactions of βglucan with the mGR. Therefore, the study was extended to evaluate its efficacy (2.5, 5 and 10 mg/kg/ i.p) in an animal model of chronic unpredictable mild stress (CUMS, 28 days) induced memory impairment. Results: Results of the current study revealed the β-glucan provided dose dependent protection against deleterious effects of stress on learning and memory associated parameters observed in Morris water maze (MWM) task. At higher tested doses, it has also significantly antagonized the stress induced weight loss and corticosterone elevation. Conclusion: From these findings, it can be deduced that the β-glucan possesses therapeutic potential against stress induced memory impairment, and this effect can be attributed to its normalizing effect on corticosterone levels.

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Conifers Phytochemicals: A Valuable Forest with Therapeutic Potential

Molecules ◽

10.3390/molecules26103005 ◽

2021 ◽

Vol 26 (10) ◽

pp. 3005

Author(s):

Kanchan Bhardwaj ◽

Ana Sanches Silva ◽

Maria Atanassova ◽

Rohit Sharma ◽

Eugenie Nepovimova ◽

...

Keyword(s):

Experimental Data ◽

Potential Role ◽

Therapeutic Potential ◽

Fungal Infections ◽

Cell Damage ◽

Cancer Growth ◽

Naturally Occurring ◽

Antioxidant Effects

Conifers have long been recognized for their therapeutic potential in different disorders. Alkaloids, terpenes and polyphenols are the most abundant naturally occurring phytochemicals in these plants. Here, we provide an overview of the phytochemistry and related commercial products obtained from conifers. The pharmacological actions of different phytochemicals present in conifers against bacterial and fungal infections, cancer, diabetes and cardiovascular diseases are also reviewed. Data obtained from experimental and clinical studies performed to date clearly underline that such compounds exert promising antioxidant effects, being able to inhibit cell damage, cancer growth, inflammation and the onset of neurodegenerative diseases. Therefore, an attempt has been made with the intent to highlight the importance of conifer-derived extracts for pharmacological purposes, with the support of relevant in vitro and in vivo experimental data. In short, this review comprehends the information published to date related to conifers’ phytochemicals and illustrates their potential role as drugs.

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Therapeutic Potential of Wogonin: A Naturally Occurring Flavonoid

CNS Drug Reviews ◽

10.1111/j.1527-3458.2005.tb00266.x ◽

2006 ◽

Vol 11 (2) ◽

pp. 141-150 ◽

Cited By ~ 78

Author(s):

Man Chun Tai ◽

Shui Ying Tsang ◽

Lawrence Y. F. Chang ◽

Hong Xue

Keyword(s):

Therapeutic Potential ◽

Naturally Occurring

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New Pharmacological Opportunities for Betulinic Acid

Planta Medica ◽

10.1055/s-0043-123472 ◽

2017 ◽

Vol 84 (01) ◽

pp. 8-19 ◽

Cited By ~ 35

Author(s):

José Ríos ◽

Salvador Máñez

Keyword(s):

Metabolic Syndrome ◽

Natural Product ◽

Betulinic Acid ◽

Therapeutic Potential ◽

Present Review ◽

Antitumor Effects ◽

Pharmacological Activities ◽

Naturally Occurring ◽

Wide Range ◽

Birch Trees

AbstractBetulinic acid is a naturally occurring pentacyclic lupane-type triterpenoid usually isolated from birch trees, but present in many other botanical sources. It is found in different plant organs, both as a free aglycon and as glycosyl derivatives. A wide range of pharmacological activities has been described for this triterpenoid, including antiviral and antitumor effects. In addition, several other interesting properties have been identified in the fields of immunity and metabolism, namely antidiabetic, antihyperlipidemic, and anti-inflammatory activities. Taken together, these latter three properties make betulinic acid a highly interesting prospect for treating metabolic syndrome. The present review focuses on the therapeutic potential of this agent, along with several of its semisynthetic derivatives, which could open new frontiers in the use of natural product-based medicines.

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Conditional guide RNA through two intermediate hairpins for programmable CRISPR/Cas9 function: building regulatory connections between endogenous RNA expressions

Nucleic Acids Research ◽

10.1093/nar/gkaa842 ◽

2020 ◽

Vol 48 (20) ◽

pp. 11773-11784

Author(s):

Jiao Lin ◽

Yan Liu ◽

Peidong Lai ◽

Huixia Ye ◽

Liang Xu

Keyword(s):

Nucleic Acid ◽

Genetic Regulation ◽

Binding Activity ◽

Strand Displacement ◽

Genetic Circuits ◽

Reporter System ◽

Gene Expressions ◽

Guide Rna ◽

Naturally Occurring ◽

Novel Approach

Abstract A variety of nanodevices developed for nucleic acid computation provide great opportunities to construct versatile synthetic circuits for manipulation of gene expressions. In our study, by employing a two-hairpin mediated nucleic acid strand displacement as a processing joint for conditional guide RNA, we aim to build artificial connections between naturally occurring RNA expressions through programmable CRISPR/Cas9 function. This two-hairpin joint possesses a sequence-switching machinery, in which a random trigger strand can be processed to release an unconstrained sequence-independent strand and consequently activate the self-inhibitory guide RNA for conditional gene regulation. This intermediate processor was characterized by the fluorescence reporter system and applied for regulation of the CRISPR/Cas9 binding activity. Using plasmids to generate this sequence-switching machinery in situ, we achieved the autonomous genetic regulation of endogenous RNA expressions controlled by other unrelated endogenous RNAs in both E. coli and human cells. Unlike previously reported strand-displacement genetic circuits, this advanced nucleic acid nanomachine provides a novel approach that can establish regulatory connections between naturally occurring endogenous RNAs. In addition to CRISPR systems, we anticipate this two-hairpin machine can serve as a general processing joint for wide applications in the development of other RNA-based genetic circuits.

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Proteasome degradation of protein C and plasmin inhibitor mutants

Thrombosis and Haemostasis ◽

10.1160/th08-04-0252 ◽

2008 ◽

Vol 100 (09) ◽

pp. 405-412 ◽

Cited By ~ 6

Author(s):

Miwako Nishio ◽

Masako Nakahara ◽

Nagisa Egawa ◽

Shinsaku Hirosawa ◽

Takatoshi Koyama

Keyword(s):

Protein C ◽

Therapeutic Potential ◽

Proteasome Inhibitors ◽

Immunoblot Analysis ◽

Mutant Proteins ◽

Intracellular Degradation ◽

Naturally Occurring ◽

Chaperone Binding ◽

Pi Deficiency ◽

Plasmin Inhibitor

SummaryProtein C (PC) deficiency and plasmin inhibitor (PI) deficiency are inherited thrombotic and haemorrhagic disorders. We investigated the intracellular degradation of mutant proteins, using naturally occurring PC and PI mutants that lead to congenital deficiencies. To examine the necessity of N-linked glycosylation for the proteasomal degradation of PC and PI, PC178 and PC331 mutants treated with tunicamycin and N-glycosylation-lacking mutants, PC92Stop and PI-America were pulse chased. The analysis revealed that the speed of degradation of the tunicamycin-treated PC mutants, PC92Stop and PI-America lacking glycosylation, was slower than that of N-glycosylated mutants. Immunoprecipitation and immunoblot analysis showed that PC178 and PC331 mutants were associated with molecular chaperones, Bip, GRP94, and calreticulin. PI-America was associated with only Bip. Although degradation of mutants was mediated by proteasomes, no association with ubiquitin was detected. Co-transfection of endoplasmic reticulum (ER) degradation enhancing α-mannosidase-like protein (EDEM) accelerated the degradation of N-glycosylated PC. In the absence of autophagy using Atg5-deficient cell lines, the degradation of the PC331 mutant was mildly accelerated but that of PC178, PI-America and PI-Okinawa mutants was not influenced. While the degradation of the PC and PI mutants was facilitated by N-glycosylation moieties, they were ubiquitin-independently degraded by proteasomes, irrespective of the presence or absence of N-glycosylation. Molecular chaperone binding was influenced by the presence of N-glycosylation moieties. When the misfolded or truncated mutant proteins are functionally active, proteasome inhibitors such as bortezomib may have therapeutic potential for treatment of protein deficiencies.

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Alterations of the endocannabinoid system and its therapeutic potential in autism spectrum disorder

Open Biology ◽

10.1098/rsob.200306 ◽

2021 ◽

Vol 11 (2) ◽

Cited By ~ 1

Author(s):

Mingyang Zou ◽

Yu Liu ◽

Shu Xie ◽

Luxi Wang ◽

Dexin Li ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Animal Model ◽

Social Preference ◽

Therapeutic Potential ◽

Hydrolytic Enzyme ◽

Endocannabinoid System ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Autistic Children ◽

Novel Approach

Autism spectrum disorder (ASD) is a group of developmental disabilities, the aetiology of which remains elusive. The endocannabinoid (eCB) system modulates neurotransmission and neuronal plasticity. Evidence points to the involvement of this neuromodulatory system in the pathophysiology of ASD. We investigated whether there is a disruption to the eCB system in ASD and whether pharmacological modulation of the eCB system might offer therapeutic potential. We examined three major components of the eCB system—endogenous cannabinoids, their receptors and associated enzymes—in ASD children as well as in the valproic acid (VPA) induced animal model in autism. Furthermore, we specifically increased 2-arachidonoylglycerol (2-AG) levels by administering JZL184, a selective inhibitor of monoacylglycerol lipase which is the hydrolytic enzyme for 2-AG, to examine ASD-like behaviours in VPA-induced rats. Results showed that autistic children and VPA-induced rats exhibited reduced eCB content, increased degradation of enzymes and upregulation of CBRs. We found that repetitive and stereotypical behaviours, hyperactivity, sociability, social preference and cognitive functioning improved after acute and chronic JZL184 treatment. The major efficacy of JZL184 was observed after administration of a dosage regimen of 3 mg kg −1 , which affected both the eCB system and ASD-like behaviours. In conclusion, a reduced eCB signalling was observed in autistic children and in the ASD animal model, and boosting 2-AG could ameliorate ASD-like phenotypes in animals. Collectively, the results suggested a novel approach to ASD treatment.

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