Pierre Fabre Dermo-Cosmétique and Personal Care, Toulouse, France.
Direction Médicale DUCRAY, Lavaur, France.
J Eur Acad Dermatol Venereol. 2023 Mar;37 Suppl 2:12-19. doi: 10.1111/jdv.18793.
Acne 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.
We evaluated the single and combined pharmacological properties of the plant extracts, Myrtus communis (Myrtacine®) and Celastrol enriched plant cell culture (CEE) extracts on the C. acnes/Th17 pathway.
The effect of Myrtacine® on the virulence of C. acnes phylotype IA1 was quantified according to the expression of several related genes. The activity of Myrtacine® 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.
Myrtacine® 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® and CEE significantly inhibited proinflammatory cytokine (IL-6, IL-8, IL-12p40 and TNF-α) 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.
2D and 3D models were developed to represent relevant and specific pathways involved in acne. Myrtacine® and CEE were shown to alter one or more of these pathways, indicating their potential beneficial effects on this disease.
痤疮是一种多因素的毛囊皮脂腺单位的炎症性疾病，其中痤疮丙酸杆菌是主要的触发因素之一。在痤疮皮肤中，痤疮丙酸杆菌表型 IA1 具有很强的优势，其生物膜结构和毒力更高，促进局部免疫炎症，特别是 Th17 途径。
我们评估了植物提取物桃金娘醇（Myrtacine®）和富含 Celastrol 的植物细胞培养物（CEE）提取物单独和联合使用对痤疮丙酸杆菌/Th17 途径的药理学特性。
根据相关基因的表达，定量评估 Myrtacine®对痤疮丙酸杆菌表型 IA1 毒力的影响。使用单核细胞衍生的树突状细胞（Mo-DC）刺激痤疮丙酸杆菌表型 IA1 的膜或生物膜，评估 Myrtacine®和 CEE 对炎症级联的活性。最后，使用痤疮丙酸杆菌刺激的皮脂细胞 2D 培养物和含有预激活 Th17 细胞的 3D 皮肤组织模型，研究 CEE 对 Th17 途径的影响。
Myrtacine®具有抗毒力作用，与未经处理的对照组相比，几种毒力因子基因的表达显著且强烈抑制了 60%-95%。Myrtacine®和 CEE 显著抑制了 Mo-DC 对痤疮丙酸杆菌表型 IA1 反应时促炎细胞因子（IL-6、IL-8、IL-12p40 和 TNF-α）的产生。有趣的是，这两种成分联合使用时，大多数细胞因子的抑制作用呈协同作用。最后，我们证明 CEE 在溶液中或在 0.3%的配方中具有抑制作用，特别是在痤疮丙酸杆菌刺激的皮脂细胞 2D 培养物中，以及在 3D 皮肤模型中整合的 Th17 淋巴细胞中，抑制了 IL-17 的释放。
建立了 2D 和 3D 模型来代表痤疮中涉及的相关和特定途径。Myrtacine®和 CEE 被证明可以改变这些途径中的一个或多个，表明它们对这种疾病可能有有益的影响。
