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      Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications


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          Curcumin, a yellow polyphenolic pigment from the Curcuma longa L. (turmeric) rhizome, has been used for centuries for culinary and food coloring purposes, and as an ingredient for various medicinal preparations, widely used in Ayurveda and Chinese medicine. In recent decades, their biological activities have been extensively studied. Thus, this review aims to offer an in-depth discussion of curcumin applications for food and biotechnological industries, and on health promotion and disease prevention, with particular emphasis on its antioxidant, anti-inflammatory, neuroprotective, anticancer, hepatoprotective, and cardioprotective effects. Bioavailability, bioefficacy and safety features, side effects, and quality parameters of curcumin are also addressed. Finally, curcumin’s multidimensional applications, food attractiveness optimization, agro-industrial procedures to offset its instability and low bioavailability, health concerns, and upcoming strategies for clinical application are also covered.

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          Pharmacology of Curcuma longa.

          The data reviewed indicate that extracts of Curcuma longa exhibit anti-inflammatory activity after parenteral application in standard animal models used for testing anti-inflammatory activity. It turned out that curcumin and the volatile oil are at least in part responsible for this action. It appears that when given orally, curcumin is far less active than after i.p. administration. This may be due to poor absorption, as discussed. Data on histamine-induced ulcers are controversial, and studies on the secretory activity (HCl, pepsinogen) are still lacking. In vitro, curcumin exhibited antispasmodic activity. Since there was a protective effect of extracts of Curcuma longa on the liver and a stimulation of bile secretion in animals, Curcuma longa has been advocated for use in liver disorders. Evidence for an effect on liver disease in humans is not yet available. From the facts that after oral application only traces of curcumin were found in the blood and that, on the other hand, most of the curcumin is excreted via the faeces it may be concluded that curcumin is absorbed poorly by the gastrointestinal tract and/or underlies presystemic transformation. Systemic effects therefore seem to be questionable after oral application except that they occur at very low concentrations of curcumin. This does not exclude a local action in the gastrointestinal tract.
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            Characteristics of compounds that cross the blood-brain barrier

            Substances cross the blood-brain barrier (BBB) by a variety of mechanisms. These include transmembrane diffusion, saturable transporters, adsorptive endocytosis, and the extracellular pathways. Here, we focus on the chief characteristics of two mechanisms especially important in drug delivery: transmembrane diffusion and transporters. Transmembrane diffusion is non-saturable and depends, on first analysis, on the physicochemical characteristics of the substance. However, brain-to-blood efflux systems, enzymatic activity, plasma protein binding, and cerebral blood flow can greatly alter the amount of the substance crossing the BBB. Transport systems increase uptake of ligands by roughly 10-fold and are modified by physiological events and disease states. Most drugs in clinical use to date are small, lipid soluble molecules that cross the BBB by transmembrane diffusion. However, many drug delivery strategies in development target peptides, regulatory proteins, oligonucleotides, glycoproteins, and enzymes for which transporters have been described in recent years. We discuss two examples of drug delivery for newly discovered transporters: that for phosphorothioate oligonucleotides and for enzymes.
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              The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery.

              Data from in vitro plasma protein binding experiments that determine the fraction of protein-bound drug are frequently used in drug discovery to guide structure design and to prioritize compounds for in vivo studies. However, we consider that these practices are usually misleading, because in vivo efficacy is determined by the free (unbound) drug concentration surrounding the therapeutic target, not by the free drug fraction. These practices yield no enhancement of the in vivo free drug concentration. So, decisions based on free drug fraction could result in the wrong compounds being advanced through drug discovery programmes. This Perspective provides guidance on the application of plasma protein binding information in drug discovery.

                Author and article information

                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                15 September 2020
                : 11
                [1] 1 Zabol Medicinal Plants Research Center, Zabol University of Medical Sciences , Zabol, Iran
                [2] 2 Department of Agriculture and Food Engineering, School of Engineering, Holy Spirit University of Kasli , Jounieh, Lebanon
                [3] 3 Faculty of Medicine, American University of Beirut , Beirut, Lebanon
                [4] 4 Institut Jean-Pierre Bourgin, AgroParisTech, INRA, Université Paris-Saclay , Versailles, France
                [5] 5 Department of Analytical and Food Chemistry, Faculty of Pharmacy, Al-Andalus University for Medical Sciences , Tartous, Syria
                [6] 6 Department of Pharmacy, University of Pisa , Pisa, Italy
                [7] 7 Interdepartmental Research Centre for Biology and Pathology of Aging, University of Pisa , Pisa, Italy
                [8] 8 Institute of Human Nutrition Sciences, Warsaw University of Life Sciences , Warszawa, Poland
                [9] 9 Noncommunicable Diseases Research Center, Bam University of Medical Sciences , Bam, Iran
                [10] 10 Student Research Committee, School of Medicine, Bam University of Medical Sciences , Bam, Iran
                [11] 11 Aromatic Plant Research Center , Lehi, UT, United States
                [12] 12 Department of Chemistry, University of Alabama in Huntsville , Huntsville, AL, United States
                [13] 13 Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [14] 14 Department of Pharmacology and Toxicology, School of Pharmacy, Shahid Beheshti University of Medical Sciences , Tehran, Iran
                [15] 15 Department of Nutrition and Dietetics, Faculty of Pharmacy, University of Concepcion , Concepcion, Chile
                [16] 16 Unidad de Desarrollo Tecnológico, UDT, Universidad de Concepción , Concepción, Chile
                [17] 17 Medical Illustration, Kendall College of Art and Design, Ferris State University , Grand Rapids, MI, United States
                [18] 18 Department of Agriculture and Food Systems, The University of Melbourne , Melbourne, VIC, Australia
                [19] 19 Department of Clinical Oncology, Queen Elizabeth Hospital , Kowloon, Hong Kong
                [20] 20 Department of Botany, University of Fort Hare , Alice, South Africa
                [21] 21 Faculty of Medicine, University of Porto , Porto, Portugal
                [22] 22 Institute for Research and Innovation in Health (i3S), University of Porto , Porto, Portugal
                Author notes

                Edited by: Michał Tomczyk, Medical University of Bialystok, Poland

                Reviewed by: Ren-You Gan, Institute of Urban Agriculture (CAAS), China; Michal Glensk, Wroclaw Medical University, Poland

                *Correspondence: Javad Sharifi-Rad, javad.sharifirad@ 123456gmail.com ; Bahare Salehi, bahar.salehi007@ 123456gmail.com ; Marc El Beyrouthy, marcelbeyrouthy@ 123456usek.edu.lb ; Miquel Martorell, mmartorell@ 123456udec.cl ; Alfred Maroyi, amaroyi@ 123456ufh.ac.za ; Natália Martins, ncmartins@ 123456med.up.pt

                This article was submitted to Ethnopharmacology, a section of the journal Frontiers in Pharmacology

                Copyright © 2020 Sharifi-Rad, Rayess, Rizk, Sadaka, Zgheib, Zam, Sestito, Rapposelli, Neffe-Skocińska, Zielińska, Salehi, Setzer, Dosoky, Taheri, El Beyrouthy, Martorell, Ostrander, Suleria, Cho, Maroyi and Martins

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 8, Tables: 3, Equations: 0, References: 229, Pages: 23, Words: 12081

                Pharmacology & Pharmaceutical medicine
                curcuma longa l.,curcuma,turmeric,spice,curcuminoids,pharmacological effects,biotechnological applications


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