In Vitro Antibacterial and Anti-Inflammatory Activity of Arctostaphylos uva-ursi Leaf Extract against Cutibacterium acnes

Cutibacterium acnes (C. acnes) is the main causative agent of acne vulgaris. The study aims to evaluate the antimicrobial activity of a natural product, Arctostaphylos uva-ursi leaf extract, against C. acnes. Preliminary chemical–physical characterization of the extract was carried out by means of FT-IR, TGA and XPS analyses. Skin permeation kinetics of the extract conveyed by a toning lotion was studied in vitro by Franz diffusion cell, monitoring the permeated arbutin (as the target component of the extract) and the total phenols by HPLC and UV-visible spectrophotometry, respectively. Antimicrobial activity and time-killing assays were performed to evaluate the effects of Arctostaphylos uva-ursi leaf extract against planktonic C. acnes. The influence of different Arctostaphylos uva-ursi leaf extract concentrations on the biofilm biomass inhibition and degradation was evaluated by the crystal violet (CV) method. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test was used to determine the viability of immortalized human keratinocytes (HaCaT) after exposure to Arctostaphylos uva-ursi leaf extract for 24 and 48 h. Levels of interleukin (IL)-1β, IL-6, IL-8 and tumour necrosis factor (TNF)-α were quantified after HaCaT cells cotreatment with Arctostaphylos uva-ursi leaf extract and heat-killed C. acnes. The minimum inhibitory concentration (MIC) which exerted a bacteriostatic action on 90% of planktonic C. acnes (MIC90) was 0.6 mg/mL. Furthermore, MIC and sub-MIC concentrations influenced the biofilm formation phases, recording a percentage of inhibition that exceeded 50 and 40% at 0.6 and 0.3 mg/mL. Arctostaphylos uva-ursi leaf extract disrupted biofilm biomass of 57 and 45% at the same concentrations mentioned above. Active Arctostaphylos uva-ursi leaf extract doses did not affect the viability of HaCaT cells. On the other hand, at 1.25 and 0.6 mg/mL, complete inhibition of the secretion of pro-inflammatory cytokines was recorded. Taken together, these results indicate that Arctostaphylos uva-ursi leaf extract could represent a natural product to counter the virulence of C. acnes, representing a new alternative therapeutic option for the treatment of acne vulgaris.

[1]  V. Casolaro,et al.  Niclosamide as a Repurposing Drug against Corynebacterium striatum Multidrug-Resistant Infections , 2022, Antibiotics.

[2]  V. Casolaro,et al.  Rhein: A novel antibacterial compound against Streptococcus mutans infection. , 2022, Microbiological research.

[3]  M. Galdiero,et al.  Pulsed laser ablation of magnetic nanoparticles as a novel antibacterial strategy against gram positive bacteria , 2022, Applied Surface Science Advances.

[4]  D. Sugier,et al.  Chemical Characteristics and Antioxidant Activity of Arctostaphylos uva-ursi L. Spreng. at the Southern Border of the Geographical Range of the Species in Europe , 2021, Molecules.

[5]  A. Piras,et al.  Combination of Two Kinds of Medicated Microparticles Based on Hyaluronic Acid or Chitosan for a Wound Healing Spray Patch , 2021, Pharmaceutics.

[6]  L. Barros,et al.  Sustainable Recovery of Preservative and Bioactive Compounds from Food Industry Bioresidues , 2021, Antioxidants.

[7]  F. Baruzzi,et al.  Innovative Eco-Friendly Hydrogel Film for Berberine Delivery in Skin Applications , 2021, Molecules.

[8]  Maria Elena Della Pepa,et al.  Postmortem interval assessment by MALDI‐TOF mass spectrometry analysis in murine cadavers , 2021, Journal of applied microbiology.

[9]  L. Altucci,et al.  Outer Membrane Vesicles Derived from Klebsiella pneumoniae Are a Driving Force for Horizontal Gene Transfer , 2021, bioRxiv.

[10]  J. Lorenzo,et al.  Fruit and Agro-Industrial Waste Extracts as Potential Antimicrobials in Meat Products: A Brief Review , 2021, Foods.

[11]  B. Dréno,et al.  Prepubertal acne: A retrospective study , 2021, International journal of women's dermatology.

[12]  N. Dupin,et al.  Cutibacterium acnes as an Opportunistic Pathogen: An Update of Its Virulence-Associated Factors , 2021, Microorganisms.

[13]  S. Boutefnouchet,et al.  In-vivo anti-inflammatory activity and safety assessment of the aqueous extract of Algerian Erica arborea L. (Ericaceae) aerial parts. , 2021, Journal of ethnopharmacology.

[14]  B. Alkhawaja,et al.  Antibiotic resistant Cutibacterium acnes among acne patients in Jordan: a cross sectional study , 2020, BMC Dermatology.

[15]  Liu Yang,et al.  Baicalin suppresses Propionibacterium acnes-induced skin inflammation by downregulating the NF-κB/MAPK signaling pathway and inhibiting activation of NLRP3 inflammasome , 2020, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[16]  Sarita Das.  Natural therapeutics for urinary tract infections—a review , 2020, Future Journal of Pharmaceutical Sciences.

[17]  H. Baldwin.  Oral Antibiotic Treatment Options for Acne Vulgaris. , 2020, The Journal of clinical and aesthetic dermatology.

[18]  J. Viruel,et al.  Phenolic Compounds Content and Genetic Diversity at Population Level across the Natural Distribution Range of Bearberry (Arctostaphylos uva-ursi, Ericaceae) in the Iberian Peninsula , 2020, Plants.

[19]  L. Sabbatini,et al.  Insights into Arbutin Effects on Bone Cells: Towards the Development of Antioxidant Titanium Implants , 2020, Antioxidants.

[20]  A. T. Nguyen,et al.  Rhein inhibits the growth of Propionibacterium acnes by blocking NADH dehydrogenase-2 activity. , 2020, Journal of medical microbiology.

[21]  B. Kocjančič,et al.  Growth detection of Cutibacterium acnes from orthopaedic implant-associated infections in anaerobic bottles from BACTEC and BacT/ALERT blood culture systems and comparison with conventional culture media. , 2019, Anaerobe.

[22]  M. Cooper,et al.  In vitro Antimicrobial Activity of Acne Drugs Against Skin-Associated Bacteria , 2019, Scientific Reports.

[23]  B. Dréno,et al.  Staphylococcus epidermidis: A Potential New Player in the Physiopathology of Acne? , 2019, Dermatology.

[24]  J. Vora,et al.  Antibacterial and antioxidant strategies for acne treatment through plant extracts , 2017, Informatics in Medicine Unlocked.

[25]  S. Nunes,et al.  Adult female acne: a guide to clinical practice* , 2019, Anais brasileiros de dermatologia.

[26]  C. Dessinioti,et al.  Recent advances in understanding Propionibacterium acnes ( Cutibacterium acnes) in acne , 2018, F1000Research.

[27]  J. Keri,et al.  Propionibacterium (Cutibacterium) acnes Bacteriophage Therapy in Acne: Current Evidence and Future Perspectives , 2018, Dermatology and Therapy.

[28]  D. Schuppan,et al.  Screening of herbal extracts for TLR2- and TLR4-dependent anti-inflammatory effects , 2018, PloS one.

[29]  Yasmine Belkaid,et al.  The human skin microbiome , 2018, Nature Reviews Microbiology.

[30]  A. Paller,et al.  A review of diagnosis and treatment of acne in adult female patients☆☆☆ , 2017, International journal of women's dermatology.

[31]  S. Abdullah,et al.  Study of the Properties of Bearberry Leaf Extract as a Natural Antioxidant in Model Foods , 2016, Antioxidants.

[32]  M. Bahmani,et al.  Medicinal Plants for the Treatment of Acne Vulgaris: A Review of Recent Evidences , 2015, Jundishapur journal of microbiology.

[33]  K Bhate,et al.  A global perspective on the epidemiology of acne , 2015, The British journal of dermatology.

[34]  K. Schaich,et al.  Re-evaluation of the 2,2-diphenyl-1-picrylhydrazyl free radical (DPPH) assay for antioxidant activity. , 2014, Journal of agricultural and food chemistry.

[35]  M. HassanHaider,et al.  Antibacterial activity of northern Ontario medicinal plant extracts , 2014 .

[36]  M. Ekor,et al.  The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety , 2014, Front. Pharmacol..

[37]  Ertuğrul H Aydemir.  Acne vulgaris. , 2014, Turk pediatri arsivi.

[38]  E. Tanghetti.  The role of inflammation in the pathology of acne. , 2013, The Journal of clinical and aesthetic dermatology.

[39]  R. Amarowicz,et al.  Inhibition of proliferation of human carcinoma cell lines by phenolic compounds from a bearberry-leaf crude extract and its fractions , 2013 .

[40]  Christopher E. Nelson,et al.  Ex vivo red blood cell hemolysis assay for the evaluation of pH-responsive endosomolytic agents for cytosolic delivery of biomacromolecular drugs. , 2013, Journal of visualized experiments : JoVE.

[41]  S. Tyski,et al.  Examination of antimicrobial activity of selected non-antibiotic medicinal preparations. , 2012, Acta poloniae pharmaceutica.

[42]  Hyo-Jong Lee,et al.  Anti-inflammatory effects of arbutin in lipopolysaccharide-stimulated BV2 microglial cells , 2012, Inflammation Research.

[43]  J. Kraft,et al.  Management of acne , 2011, Canadian Medical Association Journal.

[44]  A. Shalita,et al.  The development of antimicrobial resistance due to the antibiotic treatment of acne vulgaris: a review. , 2010, Journal of drugs in dermatology : JDD.

[45]  Y. Ishimi,et al.  Reassessment of antioxidant activity of arbutin: Multifaceted evaluation using five antioxidant assay systems , 2010, Free radical research.

[46]  A. Shalita,et al.  Acne and systemic disease. , 2009, The Medical clinics of North America.

[47]  Kaori Tanaka,et al.  Increased interferon-gamma, interleukin-12p40 and IL-8 production in Propionibacterium acnes-treated peripheral blood mononuclear cells from patient with acne vulgaris: host response but not bacterial species is the determinant factor of the disease. , 2009, Journal of dermatological science.

[48]  R. Schwartz,et al.  Minocycline-induced skin pigmentation: an update. , 2009, Acta dermatovenerologica Croatica : ADC.

[49]  B. Elewski,et al.  The prevalence of acne in adults 20 years and older. , 2008, Journal of the American Academy of Dermatology.

[50]  S. Wynn,et al.  Veterinary Herbal Medicine , 2006 .

[51]  F. Ochsendorf.  Systemic antibiotic therapy of acne vulgaris , 2006, Journal der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG.

[52]  C. Zouboulis,et al.  Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. , 2006, Microbes and infection.

[53]  Chi-Tang Ho,et al.  Phenolic compounds in foods and natural health products. , 2005 .

[54]  Boglárka Banizs,et al.  Studies on the cytotoxic effects of Propionibacterium acnes strains isolated from cornea. , 2004, Microbial pathogenesis.

[55]  S. Akira,et al.  Activation of Toll-Like Receptor 2 in Acne Triggers Inflammatory Cytokine Responses1 , 2002, The Journal of Immunology.

[56]  Masahiko Toyoda,et al.  Pathogenesis of acne , 2001, Medical Electron Microscopy.

[57]  C. Balch,et al.  Patterns of human tumor-infiltrating lymphocytes in 120 human cancers. , 1990, Archives of surgery.

[58]  D. Gerlier,et al.  Use of MTT colorimetric assay to measure cell activation. , 1986, Journal of immunological methods.

[59]  V. Dvorakova,et al.  [Antimicrobial effect of arbutin and an extract of the leaves of Arctostaphylos uva-ursi in vitro]. , 1985, Ceskoslovenska farmacie.