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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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          Most cited references236

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          Mutational landscape and significance across 12 major cancer types

          The Cancer Genome Atlas (TCGA) has used the latest sequencing and analysis methods to identify somatic variants across thousands of tumours. Here we present data and analytical results for point mutations and small insertions/deletions from 3,281 tumours across 12 tumour types as part of the TCGA Pan-Cancer effort. We illustrate the distributions of mutation frequencies, types and contexts across tumour types, and establish their links to tissues of origin, environmental/carcinogen influences, and DNA repair defects. Using the integrated data sets, we identified 127 significantly mutated genes from well-known(forexample, mitogen-activatedprotein kinase, phosphatidylinositol-3-OH kinase,Wnt/β-catenin and receptor tyrosine kinase signalling pathways, and cell cycle control) and emerging (for example, histone, histone modification, splicing, metabolism and proteolysis) cellular processes in cancer. The average number of mutations in these significantly mutated genes varies across tumour types; most tumours have two to six, indicating that the numberof driver mutations required during oncogenesis is relatively small. Mutations in transcriptional factors/regulators show tissue specificity, whereas histone modifiers are often mutated across several cancer types. Clinical association analysis identifies genes having a significant effect on survival, and investigations of mutations with respect to clonal/subclonal architecture delineate their temporal orders during tumorigenesis. Taken together, these results lay the groundwork for developing new diagnostics and individualizing cancer treatment.
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            Bioavailability of curcumin: problems and promises.

            Curcumin, a polyphenolic compound derived from dietary spice turmeric, possesses diverse pharmacologic effects including anti-inflammatory, antioxidant, antiproliferative and antiangiogenic activities. Phase I clinical trials have shown that curcumin is safe even at high doses (12 g/day) in humans but exhibit poor bioavailability. Major reasons contributing to the low plasma and tissue levels of curcumin appear to be due to poor absorption, rapid metabolism, and rapid systemic elimination. To improve the bioavailability of curcumin, numerous approaches have been undertaken. These approaches involve, first, the use of adjuvant like piperine that interferes with glucuronidation; second, the use of liposomal curcumin; third, curcumin nanoparticles; fourth, the use of curcumin phospholipid complex; and fifth, the use of structural analogues of curcumin (e.g., EF-24). The latter has been reported to have a rapid absorption with a peak plasma half-life. Despite the lower bioavailability, therapeutic efficacy of curcumin against various human diseases, including cancer, cardiovascular diseases, diabetes, arthritis, neurological diseases and Crohn's disease, has been documented. Enhanced bioavailability of curcumin in the near future is likely to bring this promising natural product to the forefront of therapeutic agents for treatment of human disease.
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              The Essential Medicinal Chemistry of Curcumin

              Curcumin is a constituent (up to ∼5%) of the traditional medicine known as turmeric. Interest in the therapeutic use of turmeric and the relative ease of isolation of curcuminoids has led to their extensive investigation. Curcumin has recently been classified as both a PAINS (pan-assay interference compounds) and an IMPS (invalid metabolic panaceas) candidate. The likely false activity of curcumin in vitro and in vivo has resulted in >120 clinical trials of curcuminoids against several diseases. No double-blinded, placebo controlled clinical trial of curcumin has been successful. This manuscript reviews the essential medicinal chemistry of curcumin and provides evidence that curcumin is an unstable, reactive, nonbioavailable compound and, therefore, a highly improbable lead. On the basis of this in-depth evaluation, potential new directions for research on curcuminoids are discussed.

                Author and article information

                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                15 September 2020
                : 11
                : 01021
                [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.

                : 15 April 2020
                : 23 June 2020
                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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