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Pharmacological Properties of Chalcones: a Review of Preclinical Including Molecular Mechanisms and Clinical Evidence

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Pharmacological Properties of Chalcones: a Review of Preclinical Including Molecular Mechanisms and Clinical Evidence REVIEW published: 18 January 2021 doi: 10.3389/fphar.2020.592654 Pharmacological Properties of Chalcones: A Review of Preclinical Including Molecular Mechanisms and Clinical Evidence Bahare Salehi 1, Cristina Quispe 2, Imane Chamkhi 3,4, Nasreddine El Omari 5, Abdelaali Balahbib 6, Javad Sharifi-Rad 7,8*, Abdelhakim Bouyahya 9*, Muhammad Akram 10, Mehwish Iqbal 11, Anca Oana Docea 12, Constantin Caruntu 13,14*, Gerardo Leyva-Gómez 15, Abhijit Dey 16*, Miquel Martorell 17,18, Daniela Calina 19*, Víctor López 20,21 and Edited by: Francisco Les 20,21 Andrei Mocan, Iuliu Hat¸ieganu University of Medicine 1Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, 2Facultad de Ciencias and Pharmacy, Romania de La Salud, Universidad Arturo Prat, Iquique, Chile, 3Faculty of Sciences, Mohammed V University of Rabat, Rabat, Morocco, Reviewed by: 4Laboratory of Plant-Microbe Interactions, AgroBioSciences, Mohammed VI Polytechnic University, Ben Guerir, Morocco, 5 Iulia Popescu, Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, 6 University of Pittsburgh, United States Rabat, Morocco, Laboratory of Zoology and General Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, 7 8 Priyia Pusparajah, Morocco, Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran, Facultad de 9 Monash University Malaysia, Malaysia Medicina, Universidad del Azuay, Cuenca, Ecuador, Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, and Genomic Center of Human Pathologies, Faculty of Medicine and Pharmacy, Mohammed V University Rabat, *Correspondence: Rabat, Morocco, 10Department of Eastern Medicine, Government College University, Faisalabad, Pakistan, 11Institute of Health Javad Sharifi-Rad Management, Dow University of Health Sciences, Karachi, Pakistan, 12Department of Toxicology, University of Medicine and javad.sharifi[email protected] Pharmacy of Craiova, Craiova, Romania, 13Department of Physiology, “Carol Davila” University of Medicine and Pharmacy, Abdelhakim Bouyahya Bucharest, Romania, 14Department of Dermatology, “Prof. N.C. Paulescu” National Institute of Diabetes, Nutrition, and Metabolic [email protected] Diseases, Bucharest, Romania, 15Departamento De Farmacia, Facultad De Química, Universidad Nacional Autónoma De México, Constantin Caruntu Ciudad De México, Mexico, 16Department of Life Sciences, Presidency University, Kolkata, India, 17Department of Nutrition and [email protected] Dietetics, Faculty of Pharmacy, and Centre for Healthy Living, University of Concepción, Concepción, Chile, 18Unidad De Abhijit Dey Desarrollo Tecnológico, UDT, Universidad De Concepción, Concepción, Chile, 19Department of Clinical Pharmacy, University of [email protected] Medicine and Pharmacy of Craiova, Craiova, Romania, 20Department of Pharmacy, Faculty of Health Sciences, Universidad San Daniela Calina Jorge, Zaragoza, Spain, 21Instituto Agroalimentario De Aragón-IA2 CITA-Universidad De Zaragoza, Zaragoza, Spain [email protected] Specialty section: Chalcones are among the leading bioactive flavonoids with a therapeutic potential This article was submitted to implicated to an array of bioactivities investigated by a series of preclinical and clinical Ethnopharmacology, fi a section of the journal studies. In this article, different scienti c databases were searched to retrieve studies Frontiers in Pharmacology depicting the biological activities of chalcones and their derivatives. This review Received: 07 August 2020 comprehensively describes preclinical studies on chalcones and their derivatives Accepted: 12 November 2020 describing their immense significance as antidiabetic, anticancer, anti-inflammatory, Published: 18 January 2021 antimicrobial, antioxidant, antiparasitic, psychoactive, and neuroprotective agents. Citation: Salehi B, Quispe C, Chamkhi I, El Besides, clinical trials revealed their use in the treatment of chronic venous Omari N, Balahbib A, Sharifi-Rad J, insufficiency, skin conditions, and cancer. Bioavailability studies on chalcones and Bouyahya A, Akram M, Iqbal M, Docea AO, Caruntu C, derivatives indicate possible hindrance and improvement in relation to its nutraceutical Leyva-Gómez G, Dey A, Martorell M, and pharmaceutical applications. Multifaceted and complex underlying mechanisms of Calina D, López V and Les F (2021) chalcone actions demonstrated their ability to modulate a number of cancer cell lines, to Pharmacological Properties of Chalcones: A Review of Preclinical inhibit a number of pathological microorganisms and parasites, and to control a number of Including Molecular Mechanisms and signaling molecules and cascades related to disease modification. Clinical studies on Clinical Evidence. Front. Pharmacol. 11:592654. chalcones revealed general absence of adverse effects besides reducing the clinical signs doi: 10.3389/fphar.2020.592654 and symptoms with decent bioavailability. Further studies are needed to elucidate their Frontiers in Pharmacology | www.frontiersin.org 1 January 2021 | Volume 11 | Article 592654 Salehi et al. Pharmacological Properties of Chalcones structure activity, toxicity concerns, cellular basis of mode of action, and interactions with other molecules. Keywords: chalcones, flavonoids, bioavailability, pharmacological studies, molecular mechanisms, clinical trials INTRODUCTION Inclusion Criteria The inclusion criteria included research studies or reviews that Chalcones are among the leading categories of flavonoids across reported the pharmacological actions of chalcones were included; the entire kingdom of plant (Hideo and Tatsurou, 1997; Abbas articles published in English, book chapters that also included et al., 2014). The term chalcone is originated from the Greek phytochemical data, and preclinical studies on cell cultures or name chalcos which means bronze. Chalcones were initially animal model with evidence of cellular and molecular manufactured in the research lab in late 1800s mechanisms of action; studies that included chalcones and (Shimokoriyama, 1962). The chalcone chemistry has created their derivatives from plants whose nomenclature is included thorough scientific research all the way through the globe in the Plant List (http://www.theplantlist.org/). (Hideo and Tatsurou, 1997). Naturally existing chalcones were not separated till the year Exclusion Criteria 1910 (Shimokoriyama, 1962). Chalcones that derived from The exclusion criteria included abstracts, case reports, and nature exist mostly as colors of petal and furthermore have conference proceedings that did not meet the inclusion been established in the heartwood, leaf, bark, fruit, and root of criteria, as well as studies that included homeopathic a range of plants and botanicals (Schroder, 1999). preparations. Chalcones are also recognized as benzyl acetophenone. Chalcones are alpha, beta unsaturated ketones holding two Data Collection fragrant rings (rings A and B) having different arrangement of Selected pharmacological studies included data on chalcones and substituents. In chalcones, two fragrant rings are connected by an their derivatives analyzed, experimental model (in vivo or aliphatic three carbon series (Rojas et al., 2002)(Figure 1). in vitro), dose, concentration, and results of pharmacological Plants containing chalcones, for instance, the Glycyrrhiza, activities with molecular mechanisms included. All information Piper, Angelica,andRuscus genus, have long been utilized as obtained and analyzed in this comprehensive and updated review therapeutic remedies in Balkan countries (Schroder, 1999; were summarized in tables and figures. Chatzopoulou et al., 2013; Maccari and Ottana, 2015). Numerous unadulterated chalcones were accepted for clinical applications or experimented in humans. PRECLINICAL PHARMACOLOGICAL Licochalcones segregated from the plant of licorice has been ACTIVITIES OF CHALCONES stated to have a range of biological activities, for instance, antispasmodic, chemopreventive, antimalarial, antitumour, Preclinical studies on chalcones and their derivatives have shown anti-inflammatory, antifungal, antioxidant, and antibacterial their high potential as antidiabetic, anticancer, anti- activities (Real, 1967; Takahashi et al., 1998). Both apples and inflammatory, antimicrobial, antioxidant, antiparasitic, sour fruits are loaded nutritional sources of dihydrochalcones psychoactive, and neuroprotective agents (Figure 2). and chalcones. Moreover, these complexes could even compose a better contribution to the overall daily consumption of Antidiabetic Activity unrefined or organic polyphenolics compounds than other In Vitro Antidiabetic Activity considerably researched flavonoids (Tomás-Barberán and Several synthetic chalcones have been reported to have potential Clifford, 2000). inhibitory activity against α-glucosidase or α-amylase. The purpose of this review is to summarize the most important pharmacological activities highlighting the cellular and molecular mechanisms of action of natural and synthetic chalcones, to better understand their therapeutic potential in the future. METHODOLOGY Search Strategy An extensive research was conducted into the available scientific databases PubMed, Scopus, Scielo, and Science Direct using the terms “chalcones,”“bioavailability,”“biological activities,”“anti- inflammatory,”“antidiabetic,”“neuroprotective,”“antioxidant,” FIGURE 1 | General chemical structure of chalcones. “anticancer,”“antibacterial,”
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