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      Natural Compounds: A Hopeful Promise as an Antibiofilm Agent Against Candida Species

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          Abstract

          The biofilm communities of Candida are resistant to various antifungal treatments. The ability of Candida to form biofilms on abiotic and biotic surfaces is considered one of the most important virulence factors of these fungi. Extracellular DNA and exopolysaccharides can lower the antifungal penetration to the deeper layers of the biofilms, which is a serious concern supported by the emergence of azole-resistant isolates and Candida strains with decreased antifungal susceptibility. Since the biofilms’ resistance to common antifungal drugs has become more widespread in recent years, more investigations should be performed to develop novel, inexpensive, non-toxic, and effective treatment approaches for controlling biofilm-associated infections. Scientists have used various natural compounds for inhibiting and degrading Candida biofilms. Curcumin, cinnamaldehyde, eugenol, carvacrol, thymol, terpinen-4-ol, linalool, geraniol, cineole, saponin, camphor, borneol, camphene, carnosol, citronellol, coumarin, epigallocatechin gallate, eucalyptol, limonene, menthol, piperine, saponin, α-terpineol, β–pinene, and citral are the major natural compounds that have been used widely for the inhibition and destruction of Candida biofilms. These compounds suppress not only fungal adhesion and biofilm formation but also destroy mature biofilm communities of Candida. Additionally, these natural compounds interact with various cellular processes of Candida, such as ABC-transported mediated drug transport, cell cycle progression, mitochondrial activity, and ergosterol, chitin, and glucan biosynthesis. The use of various drug delivery platforms can enhance the antibiofilm efficacy of natural compounds. Therefore, these drug delivery platforms should be considered as potential candidates for coating catheters and other medical material surfaces. A future goal will be to develop natural compounds as antibiofilm agents that can be used to treat infections by multi-drug-resistant Candida biofilms. Since exact interactions of natural compounds and biofilm structures have not been elucidated, further in vitro toxicology and animal experiments are required. In this article, we have discussed various aspects of natural compound usage for inhibition and destruction of Candida biofilms, along with the methods and procedures that have been used for improving the efficacy of these compounds.

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          Most cited references168

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          Hidden killers: human fungal infections.

          Although fungal infections contribute substantially to human morbidity and mortality, the impact of these diseases on human health is not widely appreciated. Moreover, despite the urgent need for efficient diagnostic tests and safe and effective new drugs and vaccines, research into the pathophysiology of human fungal infections lags behind that of diseases caused by other pathogens. In this Review, we highlight the importance of fungi as human pathogens and discuss the challenges we face in combating the devastating invasive infections caused by these microorganisms, in particular in immunocompromised individuals.
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            Curcumin: A Review of Its’ Effects on Human Health

            Turmeric, a spice that has long been recognized for its medicinal properties, has received interest from both the medical/scientific world and from culinary enthusiasts, as it is the major source of the polyphenol curcumin. It aids in the management of oxidative and inflammatory conditions, metabolic syndrome, arthritis, anxiety, and hyperlipidemia. It may also help in the management of exercise-induced inflammation and muscle soreness, thus enhancing recovery and performance in active people. In addition, a relatively low dose of the complex can provide health benefits for people that do not have diagnosed health conditions. Most of these benefits can be attributed to its antioxidant and anti-inflammatory effects. Ingesting curcumin by itself does not lead to the associated health benefits due to its poor bioavailability, which appears to be primarily due to poor absorption, rapid metabolism, and rapid elimination. There are several components that can increase bioavailability. For example, piperine is the major active component of black pepper and, when combined in a complex with curcumin, has been shown to increase bioavailability by 2000%. Curcumin combined with enhancing agents provides multiple health benefits. The purpose of this review is to provide a brief overview of the plethora of research regarding the health benefits of curcumin.
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              Invasive candidiasis

              Invasive candidiasis is an important health-care-associated fungal infection that can be caused by several Candida spp.; the most common species is Candida albicans, but the prevalence of these organisms varies considerably depending on geographical location. The spectrum of disease of invasive candidiasis ranges from minimally symptomatic candidaemia to fulminant sepsis with an associated mortality exceeding 70%. Candida spp. are common commensal organisms in the skin and gut microbiota, and disruptions in the cutaneous and gastrointestinal barriers (for example, owing to gastrointestinal perforation) promote invasive disease. A deeper understanding of specific Candida spp. virulence factors, host immune response and host susceptibility at the genetic level has led to key insights into the development of early intervention strategies and vaccine candidates. The early diagnosis of invasive candidiasis is challenging but key to the effective management, and the development of rapid molecular diagnostics could improve the ability to intervene rapidly and potentially reduce mortality. First-line drugs, including echinocandins and azoles, are effective, but the emergence of antifungal resistance, especially among Candida glabrata, is a matter of concern and underscores the need to administer antifungal medications in a judicious manner, avoiding overuse when possible. A newly described pathogen, Candida auris, is an emerging multidrug-resistant organism that poses a global threat.
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                Author and article information

                Contributors
                Journal
                Front Pharmacol
                Front Pharmacol
                Front. Pharmacol.
                Frontiers in Pharmacology
                Frontiers Media S.A.
                1663-9812
                11 July 2022
                2022
                : 13
                : 917787
                Affiliations
                [1] 1 Molecular and Medicine Research Center , Khomein University of Medical Sciences , Khomein, Iran
                [2] 2 Department of Medical Parasitology and Mycology , Arak University of Medical Sciences , Arak, Iran
                [3] 3 Microbial Biotechnology Research Center , Iran University of Medical Sciences , Tehran, Iran
                [4] 4 Department of Microbiology , School of Medicine , Iran University of Medical Sciences , Tehran, Iran
                [5] 5 Department of Laboratory Sciences , School of Paramedical Sciences , Sabzevar University of Medical Sciences , Sabzevar, Iran
                [6] 6 Cellular and Molecular Research Center , Sabzevar University of Medical Sciences , Sabzevar, Iran
                [7] 7 Student Research Committee , Khomein University of Medical Sciences , Khomein, Iran
                [8] 8 Department of Microbiology , School of Medicine , Hamadan University of Medical Sciences , Hamadan, Iran
                Author notes

                Edited by: Mustofa Mustofa, Gadjah Mada University, Indonesia

                Reviewed by: Viviane de Cássia Oliveira, University of São Paulo, Brazil

                Dr. Adnan Amin, Gomal University, Pakistan

                *Correspondence: Aref Shariati, arefshariati0111@ 123456sbmu.ac.ir ; Zahra Chegini, parisa.chegini72@ 123456gmail.com

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

                Article
                917787
                10.3389/fphar.2022.917787
                9309813
                35899117
                81b5a2af-7095-4090-878f-937938855a7e
                Copyright © 2022 Shariati, Didehdar, Razavi, Heidary, Soroush and Chegini.

                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.

                History
                : 11 April 2022
                : 30 May 2022
                Categories
                Pharmacology
                Review

                Pharmacology & Pharmaceutical medicine
                natural compounds, candida biofilm,new treatment,essential oil,antibiobilm

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