Highly Bioavailable Forms of Curcumin and Promising Avenues for Curcumin-Based Research and Application: A Review

Curcumin exerts a wide range of beneficial physiological and pharmacological activities, including antioxidant, anti-amyloid, anti-inflammatory, anti-microbial, anti-neoplastic, immune-modulating, metabolism regulating, anti-depressant, neuroprotective and tissue protective effects. However, its poor solubility and poor absorption in the free form in the gastrointestinal tract and its rapid biotransformation to inactive metabolites greatly limit its utility as a health-promoting agent and dietary supplement. Recent advances in micro- and nano-formulations of curcumin with greatly enhanced absorption resulting in desirable blood levels of the active forms of curcumin now make it possible to address a wide range of potential applications, including pain management, and as tissue protective. Using these forms of highly bioavailable curcumin now enable a broad spectrum of appropriate studies to be conducted. This review discusses the formulations designed to enhance bioavailability, metabolism of curcumin, relationships between solubility and particle size relative to bioavailability, human pharmacokinetic studies involving formulated curcumin products, the widely used but inappropriate practice of hydrolyzing plasma samples for quantification of blood curcumin, current applications of curcumin and its metabolites and promising directions for health maintenance and applications.

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The fallacy of enzymatic hydrolysis for the determination of bioactive curcumin in plasma samples as an indication of bioavailability: a comparative study

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-019-2699-x ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Sidney J. Stohs ◽

C. Y. O. Chen ◽

Harry G. Preuss ◽

Sidhartha D. Ray ◽

Luke R. Bucci ◽

...

Keyword(s):

Enzymatic Hydrolysis ◽

Human Subjects ◽

Biological Effects ◽

Curcuma Longa ◽

Free Form ◽

Pharmacokinetic Studies ◽

Plasma Samples ◽

Enhanced Absorption ◽

Poor Absorption ◽

Hydrolysis Of

Abstract Background Numerous health benefits have been demonstrated for curcumin which is extracted from turmeric (Curcuma longa L). However, due to its poor absorption in the free form in the gastrointestinal tract and rapid biotransformation, various formulations have been developed to enhance its bioavailability. Previous studies indicate that the free form of curcumin is more bioactive than its conjugated counterparts in target tissues. Most curcumin pharmacokinetics studies in humans designed to assess its absorption and bioavailability have measured and reported total (free plus conjugated) curcumin, but not free, bioactive curcumin in the plasma because enzymatic hydrolysis was employed prior to its extraction and analysis. Therefore, the bioavailability of free curcumin cannot be determined. Methods Eight human subjects (4 male, 4 female) consumed a single dose of 400 mg curcumin in an enhanced absorption formulation, and blood samples were collected over 6 h. Plasma was treated either with or without glucuronidase/sulfatase prior to extraction. Curcumin and its major metabolites were analyzed using HPLC-tandem mass spectrometry. In addition, the literature was searched for pharmacokinetic studies involving curcumin using PubMed and Google Scholar, and the reported bioavailability data were compared based on whether hydrolysis of plasma samples was used prior to sample analysis. Results Hydrolysis of blood plasma samples prior to extraction and reporting the results as “curcumin” obscures the amount of free, bioactive curcumin and total curcuminoids as compared to non-hydrolyzed samples. As a consequence, the data and biological effects reported by most pharmacokinetic studies are not a clear indication of enhanced plasma levels of free bioactive curcumin due to product formulations, leading to a misrepresentation of the results of the studies and the products when enzymatic hydrolysis is employed. Conclusions When enzymatic hydrolysis is employed as is the case with most studies involving curcumin products, the amount of free bioactive curcumin is unknown and cannot be determined. Therefore, extreme caution is warranted in interpreting published analytical results from biological samples involving ingestion of curcumin-containing products. Trial registration ClinicalTrails.gov, trial identifying number NCT04103788, September 24, 2019. Retrospectively registered.

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Genetic Differentiation in Anthocyanin Content among Berry Fruits

Current Issues in Molecular Biology ◽

10.3390/cimb43010004 ◽

2021 ◽

Vol 43 (1) ◽

pp. 36-51

Author(s):

Alicja Ponder ◽

Ewelina Hallmann ◽

Martyna Kwolek ◽

Dominika Średnicka-Tober ◽

Renata Kazimierczak

Keyword(s):

Essential Role ◽

Positive Impact ◽

Skin Pigmentation ◽

Highbush Blueberry ◽

Anthocyanin Content ◽

Healthy Nutrition ◽

Wide Range ◽

Health Promoting ◽

Berry Fruits ◽

Red Currant

Anthocyanins are widely distributed secondary metabolites that play an essential role in skin pigmentation of many plant organs and microorganisms. Anthocyanins have been associated with a wide range of biological and pharmacological properties. They are also effective agents in the prevention and treatment of many chronic diseases. Berries are particularly abundant in these compounds; therefore, their dietary intake has health-promoting effects. The aim of this study was to identify and determine the anthocyanin content in selected species and cultivars of berry fruits, such as raspberry, blackberry, red currant, blackcurrant, and highbush blueberry, widely consumed by Europeans. The concentrations of anthocyanins were determined by HPLC, identifying individual compounds: cyanidin-3-O-glucoside, pelargonidin-3-O-glucoside, delphinidin-3-O-glucoside, delphinidin-3-O-rutinoside, cyanidin-3-O-rutinoside, delphinidin-3-O-galactoside, cyanidin-3-O-galactoside, and malvidin-3-O-galactoside. The experimental data showed that the selected species and cultivars of berry fruits differ significantly in the contents of anthocyanins. Among all species tested, blackberry and blackcurrant were characterized significantly by the highest content of anthocyanins (sum), while the lowest content was found in red currant fruits. Additionally, the content of individual anthocyanin compounds in particular species and cultivars was also different. Considering the high content of anthocyanins and their potential positive impact on human health and protection against disease, berries should be part of healthy nutrition.

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Enhanced Bilosomal Properties Resulted in Optimum Pharmacological Effects by Increased Acidification Pathways

Pharmaceutics ◽

10.3390/pharmaceutics13081184 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1184

Author(s):

Armin Mooranian ◽

Thomas Foster ◽

Corina M Ionescu ◽

Daniel Walker ◽

Melissa Jones ◽

...

Keyword(s):

Bile Acids ◽

Biological Effects ◽

Cellular Respiration ◽

Full Potential ◽

Protective Effects ◽

Pharmacological Effects ◽

Β Cells ◽

Positive Effects ◽

Wide Range ◽

Anti Inflammatory

Introduction: Recent studies in our laboratory have shown that some bile acids, such as chenodeoxycholic acid (CDCA), can exert cellular protective effects when encapsulated with viable β-cells via anti-inflammatory and anti-oxidative stress mechanisms. However, to explore their full potential, formulating such bile acids (that are intrinsically lipophilic) can be challenging, particularly if larger doses are required for optimal pharmacological effects. One promising approach is the development of nano gels. Accordingly, this study aimed to examine biological effects of various concentrations of CDCA using various solubilising nano gel systems on encapsulated β-cells. Methods: Using our established cellular encapsulation system, the Ionic Gelation Vibrational Jet Flow technology, a wide range of CDCA β-cell capsules were produced and examined for morphological, biological, and inflammatory profiles. Results and Conclusion: Capsules’ morphology and topographic characteristics remained similar, regardless of CDCA or nano gel concentrations. The best pharmacological, anti-inflammatory, and cellular respiration, metabolism, and energy production effects were observed at high CDCA and nano gel concentrations, suggesting dose-dependent cellular protective and positive effects of CDCA when incorporated with high loading nano gel.

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A Slot-Die Technique for the Preparation of Continuous, High-Area, Chitosan-Based Thin Films

Polymers ◽

10.3390/polym13101566 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1566

Author(s):

Oliver J. Pemble ◽

Maria Bardosova ◽

Ian M. Povey ◽

Martyn E. Pemble

Keyword(s):

Thin Films ◽

Mechanical Properties ◽

High Volume ◽

Mechanical Anisotropy ◽

Diverse Range ◽

Direction Parallel ◽

High Area ◽

Wide Range ◽

Slot Die ◽

Potential Applications

Chitosan-based films have a diverse range of potential applications but are currently limited in terms of commercial use due to a lack of methods specifically designed to produce thin films in high volumes. To address this limitation directly, hydrogels prepared from chitosan, chitosan-tetraethoxy silane, also known as tetraethyl orthosilicate (TEOS) and chitosan-glutaraldehyde have been used to prepare continuous thin films using a slot-die technique which is described in detail. By way of preliminary analysis of the resulting films for comparison purposes with films made by other methods, the mechanical strength of the films produced was assessed. It was found that as expected, the hybrid films made with TEOS and glutaraldehyde both show a higher yield strength than the films made with chitosan alone. In all cases, the mechanical properties of the films were found to compare very favorably with similar measurements reported in the literature. In order to assess the possible influence of the direction in which the hydrogel passes through the slot-die on the mechanical properties of the films, testing was performed on plain chitosan samples cut in a direction parallel to the direction of travel and perpendicular to this direction. It was found that there was no evidence of any mechanical anisotropy induced by the slot die process. The examples presented here serve to illustrate how the slot-die approach may be used to create high-volume, high-area chitosan-based films cheaply and rapidly. It is suggested that an approach of the type described here may facilitate the use of chitosan-based films for a wide range of important applications.

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Health Benefits of Uses and Applications of Moringa oleifera in Bakery Products

Plants ◽

10.3390/plants10020318 ◽

2021 ◽

Vol 10 (2) ◽

pp. 318

Author(s):

Paula García Milla ◽

Rocío Peñalver ◽

Gema Nieto

Keyword(s):

Moringa Oleifera ◽

Essential Amino Acids ◽

Bakery Products ◽

Unani Medicine ◽

Functional Value ◽

Organoleptic Characteristics ◽

Wide Range ◽

Potential Applications ◽

Medicinal Properties ◽

Excellent Source

Moringa oleifera belongs to the Moringaceae family and is the best known of the native Moringa oleifera genus. For centuries, it has been used as a system of Ayurvedic and Unani medicine and has a wide range of nutritional and bioactive compounds, including proteins, essential amino acids, carbohydrates, lipids, fibre, vitamins, minerals, phenolic compounds, phytosterols and others. These characteristics allow it to have pharmacological properties, including anti-diabetic, anti-inflammatory, anticarcinogenic, antioxidant, cardioprotective, antimicrobial and hepatoprotective properties. The entire Moringa oleifera plant is edible, including its flowers, however, it is not entirely safe, because of compounds that have been found mainly in the root and bark, so the leaf was identified as the safest. Moringa oleifera is recognised as an excellent source of phytochemicals, with potential applications in functional and medicinal food preparations due to its nutritional and medicinal properties; many authors have experimented with incorporating it mainly in biscuits, cakes, brownies, meats, juices and sandwiches. The results are fascinating, as the products increase their nutritional value; however, the concentrations cannot be high, as this affects the organoleptic characteristics of the supplemented products. The aim of this study is to review the application of Moringa oleifera in bakery products, which will allow the creation of new products that improve their nutritional and functional value.

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Sporulation in solventogenic and acetogenic clostridia

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11289-9 ◽

2021 ◽

Author(s):

Mamou Diallo ◽

Servé W. M. Kengen ◽

Ana M. López-Contreras

Keyword(s):

Current Knowledge ◽

Carbon Sources ◽

Cost Effective ◽

Biotechnological Production ◽

Key Points ◽

Wide Range ◽

Potential Applications ◽

A Cell ◽

Sporulation Initiation ◽

Solventogenic Clostridia

AbstractThe Clostridium genus harbors compelling organisms for biotechnological production processes; while acetogenic clostridia can fix C1-compounds to produce acetate and ethanol, solventogenic clostridia can utilize a wide range of carbon sources to produce commercially valuable carboxylic acids, alcohols, and ketones by fermentation. Despite their potential, the conversion by these bacteria of carbohydrates or C1 compounds to alcohols is not cost-effective enough to result in economically viable processes. Engineering solventogenic clostridia by impairing sporulation is one of the investigated approaches to improve solvent productivity. Sporulation is a cell differentiation process triggered in bacteria in response to exposure to environmental stressors. The generated spores are metabolically inactive but resistant to harsh conditions (UV, chemicals, heat, oxygen). In Firmicutes, sporulation has been mainly studied in bacilli and pathogenic clostridia, and our knowledge of sporulation in solvent-producing or acetogenic clostridia is limited. Still, sporulation is an integral part of the cellular physiology of clostridia; thus, understanding the regulation of sporulation and its connection to solvent production may give clues to improve the performance of solventogenic clostridia. This review aims to provide an overview of the triggers, characteristics, and regulatory mechanism of sporulation in solventogenic clostridia. Those are further compared to the current knowledge on sporulation in the industrially relevant acetogenic clostridia. Finally, the potential applications of spores for process improvement are discussed.Key Points• The regulatory network governing sporulation initiation varies in solventogenic clostridia.• Media composition and cell density are the main triggers of sporulation.• Spores can be used to improve the fermentation process.

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Role of Insulin in Health and Disease: An Update

International Journal of Molecular Sciences ◽

10.3390/ijms22126403 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6403

Author(s):

Md Saidur Rahman ◽

Khandkar Shaharina Hossain ◽

Sharnali Das ◽

Sushmita Kundu ◽

Elikanah Olusayo Adegoke ◽

...

Keyword(s):

Insulin Signaling ◽

Basic Research ◽

Future Research ◽

Protective Effects ◽

Glucose Levels ◽

Physiological Processes ◽

Blood Glucose Levels ◽

Wide Range ◽

Health And Disease

Insulin is a polypeptide hormone mainly secreted by β cells in the islets of Langerhans of the pancreas. The hormone potentially coordinates with glucagon to modulate blood glucose levels; insulin acts via an anabolic pathway, while glucagon performs catabolic functions. Insulin regulates glucose levels in the bloodstream and induces glucose storage in the liver, muscles, and adipose tissue, resulting in overall weight gain. The modulation of a wide range of physiological processes by insulin makes its synthesis and levels critical in the onset and progression of several chronic diseases. Although clinical and basic research has made significant progress in understanding the role of insulin in several pathophysiological processes, many aspects of these functions have yet to be elucidated. This review provides an update on insulin secretion and regulation, and its physiological roles and functions in different organs and cells, and implications to overall health. We cast light on recent advances in insulin-signaling targeted therapies, the protective effects of insulin signaling activators against disease, and recommendations and directions for future research.

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Click Chemistry Enabling Covalent and Non-Covalent Modifications of Graphene with (Poly)saccharides

Polymers ◽

10.3390/polym13010142 ◽

2020 ◽

Vol 13 (1) ◽

pp. 142

Author(s):

Hu Li ◽

Raffaello Papadakis

Keyword(s):

Click Chemistry ◽

Life Science ◽

Environmental Applications ◽

Energy Materials ◽

Sensors And Actuators ◽

Polar Solvents ◽

Wide Range ◽

Potential Applications ◽

Covalent Modifications

Graphene is a material with outstanding properties and numerous potential applications in a wide range of research and technology areas, spanning from electronics, energy materials, sensors, and actuators to life-science and many more. However, the insolubility and poor dispersibility of graphene are two major problems hampering its use in certain applications. Tethering mono-, di-, or even poly-saccharides on graphene through click-chemistry is gaining more and more attention as a key modification approach leading to new graphene-based materials (GBM) with improved hydrophilicity and substantial dispersibility in polar solvents, e.g., water. The attachment of (poly)saccharides on graphene further renders the final GBMs biocompatible and could open new routes to novel biomedical and environmental applications. In this review, recent modifications of graphene and other carbon rich materials (CRMs) through click chemistry are reviewed.

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Neurological Alterations and Testicular Damages in Aging Induced by D-Galactose and Neuro and Testicular Protective Effects of Combinations of Chitosan Nanoparticles, Resveratrol and Quercetin in Male Mice

Coatings ◽

10.3390/coatings11040435 ◽

2021 ◽

Vol 11 (4) ◽

pp. 435

Author(s):

Reham Z. Hamza ◽

Mohammad S. Al-Harbi ◽

Munirah A. Al-Hazaa

Keyword(s):

Oxidative Stress ◽

Chitosan Nanoparticles ◽

Oxidative Stress Marker ◽

Control Group ◽

Antioxidant Enzyme Activities ◽

Enzymatic Antioxidants ◽

Protective Effects ◽

Biochemical Alterations ◽

Wide Range ◽

Neurological Alterations

Aging is a neurological disease that is afforded by incidence of oxidative stress. Chitosan has received global interests due to its wide medical uses. Quercetin (Q) is a bioflavonoid and widely distributed in vegetables and fruits. Resveratrol is considered as a potent antioxidant and is a component of a wide range of foods. The using of either chitosan nanopartciles (CH-NPs), querectin (Q), and resveratrol (RV) to reduce the oxidative stress and biochemical alterations on brain and testicular tissues induced by D-galactose (DG) (100 mg/Kg) were the aim of the present study. This study investigated the probable protective effects of CH-NPs in two doses (140,280 mg/Kg), Q (20 mg/Kg) and RV (20 mg/Kg), against DG induced aging and neurological alterations. Brain antioxidant capacity as malonaldehyde (MDA), catalase (CAT), and glutathione reductase (GRx), as well as histopathological damages of the brain and testicular tissues were measured. The DG treated group had significantly elevated the oxidative stress markers by 96% and 91.4% in brain and testicular tissues respectively and lower significantly the antioxidant enzyme activities of both brain and testicular tissues than those of the control group by 86.95%, 69.27%, 83.07%, and 69.43%. Groups of DG that treated with a combination of CH-NPs in two doses, Q and RV, the levels of oxidative stress marker declined significantly by 68.70%, 76.64% in brain tissues and by 74.07% and 76.61% in testicular tissues, and the enzymatic antioxidants increased significantly by 75.55%, 79.24%, 62.32%, and 61.97% as compared to the DG group. The present results indicate that CH-NPs, Q, and RV have protective effects against DG-induced brain and testis tissue damage at the biochemical and histopathological levels. Mechanisms of this protective effect of used compounds against neurological and testicular toxicity may be due to the enhanced brain and testis antioxidant capacities.

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A longitudinal study of suicide and suicide attempt in northwest of Iran: incidence, predictors, and socioeconomic status and the role of sociocultural status

BMC Public Health ◽

10.1186/s12889-021-11527-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ali Fakhari ◽

Mostafa Farahbakhsh ◽

Elham Davtalab Esmaeili ◽

Hosein Azizi

Keyword(s):

Socioeconomic Status ◽

Longitudinal Study ◽

Religious Commitment ◽

Incidence Rates ◽

Demographic Characteristics ◽

Protective Effects ◽

Wide Range ◽

Multiple Variable ◽

History Of

Abstract Background A detailed community-level understanding of socioeconomic status (SES) and sociocultural status (SCS) of suicides and suicide attempters (SAs) in a prospective design could have significant implications for policymakers at the local prevention and treatment levels. The effect of SCS and SES on SAs is poorly understood and investigated in Iran. The present study aimed to investigate the incidence, trend, and role of SES and SCS on suicide and SAs. Methods A longitudinal study was conducted based on the registry for SAs in Malekan County, Iran, from 2015 to 2018. Demographic characteristics, SES, SCS, incidence rates, and predictors of suicidal behaviors were measured via structured instruments. Simple and multiple logistic regressions were used to estimate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Results A total of 853 SAs (32 suicides and 821 attempts) were identified during the study. Trend analysis revealed that the suicide rate significantly decreased from 2014 (10.28) to 2018 (1.75) per 100,000. In the final multiple variable models, age (26–40), male sex, unemployment, antisocial activities, history of SA, hanging method, and season (spring) increased the suicide risk while religious commitment had protective effects on suicide. Conclusions Our findings indicated that demographic characteristics, low SES, and SCS are associated with suicide. In this county, trend of suicide and SA were decreased from 2014 to 2018. This study findings highlight the need to consider a wide range of contextual variables, socio-demographic, SES, and SCS in suicide prevention strategies. Improving inter-sectoral collaborations and policymakers’ attitudes are imperative for SA reduction.

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