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Anti-Acne Activity of Italian Medicinal Plants Used for Skin Infection Kate Nelson, Emory University School of Medicine James T

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Anti-Acne Activity of Italian Medicinal Plants Used for Skin Infection Kate Nelson, Emory University School of Medicine James T Anti-acne activity of Italian medicinal plants used for skin infection Kate Nelson, Emory University School of Medicine James T. Lyles, Emory University Tracy Li, Emory University Alessandro Saitta, Universita degli Studi di Palermo Eugenia Addie-Noye, Emory University Paula Tyler, Emory University Cassandra Quave, Emory University Journal Title: Frontiers in Pharmacology Volume: Volume 7, Number NOV Publisher: Frontiers Media | 2016-11-10, Pages 425-425 Type of Work: Article | Final Publisher PDF Publisher DOI: 10.3389/fphar.2016.00425 Permanent URL: https://pid.emory.edu/ark:/25593/rtfc8 Final published version: http://dx.doi.org/10.3389/fphar.2016.00425 Copyright information: © 2016 Nelson, Lyles, Li, Saitta, Addie-Noye, Tyler and Quave. This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/). Accessed September 25, 2021 1:00 AM EDT ORIGINAL RESEARCH published: 10 November 2016 doi: 10.3389/fphar.2016.00425 Anti-Acne Activity of Italian Medicinal Plants Used for Skin Infection Kate Nelson 1, James T. Lyles 2, Tracy Li 2, Alessandro Saitta 3, Eugenia Addie-Noye 2, Paula Tyler 4 and Cassandra L. Quave 1, 2, 5* 1 Department of Dermatology, Emory University School of Medicine, Atlanta, GA, USA, 2 Center for the Study of Human Health, Emory University College of Arts and Sciences, Atlanta, GA, USA, 3 Department of Agricultural and Forest Sciences, Università Degli Studi di Palermo, Palermo, Italy, 4 Department of Chemistry, Emory University College of Arts and Sciences, Atlanta, GA, USA, 5 Antibiotic Resistance Center, Emory University, Atlanta, GA, USA Propionibacterium acnes is implicated in the pathogenesis of acne vulgaris, which impacts >85% of teenagers. Novel therapies are in high demand and an ethnopharmacological approach to discovering new plant sources of anti-acne therapeutics could contribute to filling this void in effective therapies. The aims of our study were two-fold: (1) To determine if species identified in ethnopharmacological field studies as having traditional uses for skin and soft tissue infection (SSTI) exhibit significantly more activity against P.acnes than species with no such reported use; and (2) Chemically characterize active extracts and assess their suitability for future investigation. Extracts of Italian medicinal (for acne and other skin infection) and randomly collected Edited by: plants and fungi were screened for growth-inhibitory and anti-biofilm activity in P. acnes Adolfo Andrade-Cetto, using broth microdilution methods. Bioactive extracts were chemically characterized by National Autonomous University of Mexico, Mexico HPLC and examined for cytotoxicity against human keratinocytes (HaCaTs). Following Reviewed by: evaluation of 157 extracts from 10 fungi and 58 plants, we identified crude extracts from Tom Coenye, seven species exhibiting growth inhibitory activity (MICs 64–256 µg mL−1). All active Ghent University, Belgium Adeyemi Oladapo Aremu, extracts were examined for cytotoxicity against HaCaTs; extracts from one fungal and −1 University of KwaZulu-Natal, one plant species were toxic (IC50 256 µg mL ). HPLC analysis with chemical standards South Africa revealed many of these extracts contained chlorogenic acid, p-coumaric acid, ellagic *Correspondence: acid, gallic acid, and tannic acid. In conclusion, species used in traditional medicine for Cassandra L. Quave [email protected] the skin exhibited significantly greater (p < 0.05) growth inhibitory and biofilm eradication activity than random species, supporting the validity of an ethnobotanical approach to Specialty section: identifying new therapeutics. The anti-acne activity of three extracts is reported for the This article was submitted to Ethnopharmacology, first time: Vitis vinifera leaves, Asphodelus microcarpus leaves, and Vicia sativa aerial a section of the journal parts. Frontiers in Pharmacology Keywords: biofilms, antimicrobials, antibiotics, acne, medicinal plants, Propionibacterium acnes, Received: 30 August 2016 ethnopharmacology Accepted: 26 October 2016 Published: 10 November 2016 Citation: INTRODUCTION Nelson K, Lyles JT, Li T, Saitta A, Addie-Noye E, Tyler P and Quave CL Acne vulgaris is a common skin disorder affecting more than 85% of teenagers in the United (2016) Anti-Acne Activity of Italian Medicinal Plants Used for Skin States (James et al., 2009). While it is not a lethal or debilitating disorder, it can be painful Infection. Front. Pharmacol. 7:425. and disfiguring, causing significant physiological distress, and heavy economic burden. Acne is doi: 10.3389/fphar.2016.00425 associated with increases in anxiety, depression, and suicidal ideation (Dunn et al., 2011). In 2001, Frontiers in Pharmacology | www.frontiersin.org 1 November 2016 | Volume 7 | Article 425 Nelson et al. Anti-Acne Activity of Italian Plants and Fungi a report estimated that over $1 billion is spent each year in the US plant species of which 31 had an ethnobotanical use and on acne related health care visits and acne therapies (Lehmann 32 were random collections. The random collection extracts et al., 2001). However, these therapies are not cures, but rather had no vasorelaxation activity, but 19% of ethnobotanical ways of managing this follicular disorder. extracts did (Slish et al., 1999). Another study focused on Current treatments fall into either two categories: topical the search for antifungal activity compared 114 extracts with or oral. Common topical treatments include benzoyl peroxide, antifungal ethnobotanical use and 183 extracts with either no retinoids, and antibiotics (i.e., erythromycin or clindamycin), ethnobotanical indication or non-fungal ethnobotanical use. In and common oral treatments include retinoids and antibiotics a series of bioassays, extracts in the ethnobotanical indication (i.e., tetracycline and macrolides; Layton, 2016; Zaenglein et al., group consistently had higher hit rates with the antifungal 2016). In cases of severe acne, combinational treatments are used, indicated extracts; 40% had antifungal activity against at least usually employing benzoyl peroxide, retinoids, and/or antibiotics one fungus vs. 21% of plants with no anti-fungal ethnobotanical together (Layton, 2016; Zaenglein et al., 2016). Antibiotics have use (Svetaz et al., 2010). Similarly, a study comparing three been used for over 50 years to treat acne and today one course of groups, skin and soft tissue infection (SSTI) botanicals, non-skin topical or systemic treatment typically lasts 3–6 months (Walsh botanicals, and random plants, for their Staphylococcus aureus et al., 2016). Antibiotics are thought to inhibit inflammation antibacterial and anti-biofilm actions found no difference indicative of acne when used topically and systemically, as well as between the three groups for antibacterial activity, but SSTI target P. acnes when used topically (Walsh et al., 2016). Like many ethnobotanicals had more anti-biofilm potential in S. aureus other bacteria, P. acnes is also subject to emerging antibiotic models than the random collections (Quave et al., 2008a). resistance and novel therapies are in high demand worldwide Investigating antibacterial bioactivities beyond bacteriostatic or (Sardana et al., 2015; Del Rosso and Zeichner, 2016; Walsh et al., bactericidal action, such as pathogenesis factors, could reveal 2016). Pathogenesis targets, such as quorum sensing and biofilms, other mechanisms through which plant secondary metabolites are organism specific and could limit resistance development impact pathogen survival and fitness, increasing the chance of (LaSarre and Federle, 2013). discovering new therapeutics. For the purposes of clarity, here we Biofilms contribute to the recalcitrant nature of acne by use SSTI to refer to infections of the skin and soft tissues ranging presenting a physical barrier to which few molecules are capable from mild to severe, including those that are purulent (acne, of penetrating, allowing the bacteria within to persist and cause furuncles, abscesses, carbuncles) to non-purulent (necrotizing infection (Donlan, 2001; Vlassova et al., 2011). Biofilms have been infection, cellulitis, erysipelas) in nature. implicated in implant-related and chronic infections (Donlan, Our research group has already demonstrated interesting 2001; Aubin et al., 2014), accounting for an estimated 80% of anti-staphylococcal activity (in terms of growth, biofilm, and microbial infections in the body (Sun et al., 2013). P. acnes has quorum sensing inhibitory action) in the Quave Natural Products been detected in biofilms associated with bone, joint and spinal Library (QNPL), which includes a collection of plant and fungal prosthetics, breast implants, external ventricular shunts, and, extracts derived from natural ingredients used specifically in the in rare instances, cardiac devices (Aubin et al., 2014). P. acnes treatment of SSTIs—caused by a number of skin pathogenic biofilms are associated with pathogenesis of acne, with extensive bacteria, including Propionibacterium acnes—and other health biofilm growth being associated with acne vulgaris (Jahns and concerns in the Mediterranean and other parts of the world Alexeyev, 2014). The high incidence of antibiotic resistance seen (Quave et al., 2012, 2015). Extracts from Italian species in in P. acnes worldwide is thought to be due to biofilms, as well the QNPL are uniquely tied to ethnopharmacological data as the high use of antibiotics (Sardana et al., 2015; Walsh et al., documented in
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