Myrtus communis and Celastrol enriched plant cell culture extracts control together the pivotal role of Cutibacterium acnes and inflammatory pathways in acne

IntroductionAcne is a multifactorial inflammatory disease of the pilosebaceous unit in which Cutibacterium acnes is one of the main triggers. A strong predominance of C. acnes phylotype IA1 is present in acne skin with higher biofilm organization and virulence, promoting local immuno-inflammation, especially the Th17 pathway. ObjectivesWe evaluated the single and combined pharmacological properties of the plant extracts, Myrtus communis (Myrtacine (R)) and Celastrol enriched plant cell culture (CEE) extracts on the C. acnes/Th17 pathway. MethodsThe effect of Myrtacine (R) on the virulence of C. acnes phylotype IA1 was quantified according to the expression of several related genes. The activity of Myrtacine (R) and CEE on the inflammatory cascade was assessed using monocytes-derived dendritic cells (Mo-DC) stimulated with membranes or biofilms of the C. acnes phylotype IA1. Finally, the effect of CEE on the Th17 pathway was studied using C. acnes stimulated sebocyte 2D cultures and 3D skin tissue models containing preactivated Th17 cells. ResultsMyrtacine (R) had an anti-virulence effect, evident as a significant and strong inhibition of the expression of several virulence factor genes by 60%-95% compared to untreated controls. Myrtacine (R) and CEE significantly inhibited proinflammatory cytokine (IL-6, IL-8, IL-12p40 and TNF-alpha) production by Mo-DC in response to C. acnes phylotype IA1. Interestingly, these two ingredients resulted in synergistic inhibition of most cytokines when used in combination. Finally, we demonstrated an inhibitory effect of CEE, in solution or formulated at 0.3%, specifically on IL-17 release by Th17 lymphocytes in a C. acnes-stimulated sebocyte 2D cultures and by Th17-lymphocytes integrated in a 3D skin models. Conclusions2D and 3D models were developed to represent relevant and specific pathways involved in acne. Myrtacine (R) and CEE were shown to alter one or more of these pathways, indicating their potential beneficial effects on this disease.