AUTHOR=De Canha Marco Nuno , Komarnytsky Slavko , Langhansova Lenka , Lall Namrita 

TITLE=Exploring the Anti-Acne Potential of Impepho [Helichrysum odoratissimum (L.) Sweet] to Combat Cutibacterium acnes Virulence

JOURNAL=Frontiers in Pharmacology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.01559

DOI=10.3389/fphar.2019.01559

ISSN=1663-9812

ABSTRACT=<p>The Gram-positive bacterium <italic>Cutibacterium acnes</italic> (previously <italic>Propionibacterium acnes</italic>), plays an important role in the pathogenesis and progression of the dermatological skin disorder acne vulgaris. The methanolic extract of <italic>Helichrysum odoratissimum</italic> (L.) Sweet (HO-MeOH) was investigated for its ability to target bacterial growth and pathogenic virulence factors associated with acne progression. The gas chromatography–mass spectrometry (GC-MS) analysis of HO-MeOH identified <italic>α</italic>-humulene (3.94%), <italic>α</italic>-curcumene (3.74%), and caryophyllene (8.12%) as major constituents, which correlated with previous reports of other <italic>Helichrysum</italic> species. The HO-MeOH extract exhibited potent antimicrobial activity against <italic>C. acnes</italic> (ATCC 6919) with a minimum inhibitory concentration (MIC) of 7.81 µg/ml. It enhanced the antimicrobial activity of benzoyl peroxide (BPO). The extract showed high specificity against <italic>C</italic>. <italic>acnes</italic> cell aggregation at sub-inhibitory concentrations, preventing biofilm formation. Mature <italic>C</italic>. <italic>acnes</italic> biofilms were disrupted at a sub-inhibitory concentration of 3.91 µg/ml. At 100 µg/ml, HO-MeOH reduced interleukin-1α (IL-1α) cytokine levels in <italic>C</italic>. <italic>acnes</italic>-induced human keratinocytes (HaCaT) by 11.08%, highlighting its potential as a comedolytic agent for the treatment of comedonal acne. The extract exhibited a 50% inhibitory concentration (IC<sub>50</sub>) of 157.50 µg/ml against lipase enzyme activity, an enzyme responsible for sebum degradation, ultimately causing inflammation. The extract’s anti-inflammatory activity was tested against various targets associated with inflammatory activation by the bacterium. The extract inhibited pro-inflammatory cytokine levels of IL-8 by 48.31% when compared to <italic>C</italic>. <italic>acnes</italic>-induced HaCaT cells at 7.81 µg/ml. It exhibited cyclooxygenase-II (COX-II) enzyme inhibition with an IC<sub>50</sub> of 22.87 µg/ml. Intracellular nitric oxide (NO) was inhibited by 40.39% at 7.81 µg/ml when compared with NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The intracellular NO inhibition was potentially due to the 2.14 fold reduction of inducible nitric oxide synthase (iNOS) gene expression. The HO-MeOH extract exhibited an IC<sub>50</sub> of 145.45 µg/ml against virulent hyaluronidase enzyme activity, which is responsible for hyaluronan degradation and scar formation. This study provides scientific validation for the traditional use of <italic>H. odoratissimum</italic> as an ointment for pimples, not only due to its ability to control <italic>C</italic>. <italic>acnes</italic> proliferation but also due to its inhibitory activity on various targets associated with bacterial virulence leading to acne progression.</p>