Acne is a chronic multifactorial pathology characterized by the appearance of non-inflammatory retentional lesions, e.g., open and closed comedones, and inflammatory lesions including papules, pustules, nodules and cysts. It affects approximately 80% of teenagers worldwide1 and is one of the most frequently cited reasons for dermatological appointments.
Although teenage acne normally disappears around the age of 20, recent epidemiological studies have confirmed its substantial prevalence in adult women; about 40% of women affected are 25 and older.2, 3 Various factors are involved in its appearance or aggravation, including genetics, hormone changes and lifestyle.4
From a biological standpoint, the appearance of acne lesions results from the dysfunction of several mechanisms in the pilosebaceous follicle. Four of these include modifications of sebum and microbiota, hyperkeratinization and inflammation, described below (see Figure 1).
Sebaceous gland activity: Acne is a pathology characterized by quantitative and qualitative modifications of sebum. Sebaceous gland metabolism is activated by endogenous factors, e.g., hormones, Cutibacterium acnes, and lipophagic activity, and exogenous factors such as stress. This causes a modification of the lipid profile in sebum and its abnormally high production.5-8
Hyperkeratinization: Hyperkeratinization is a biological event occurring early in the development of acne lesions. It is characterized by the abnormal proliferation and keratinization of follicle keratinocytes that cause an obstruction of the excreting canal. Excess sebum produced cannot be evacuated and so the pilosebaceous canal becomes dilated.9
Modification of the microbiota: The bacterial species C. acnes is one of the major pathogenic factors contributing to the development of acne. As a result of the high quantity of sebum and low oxygen concentration, the microcomedo is an environment favorable to the growth of this microorganism.
Recent studies have led to the identification of several sub-types of C. acnes, or phylotypes, with variable degrees of virulence. In cases of acne, a loss of phylotype diversity of C. acnes with a shift toward phylotype IA1 has been observed.10-13 Phylotype IA1 bacteria can communicate using a system called quorum sensing, thereby favoring the expression of virulence factors, e.g., formation of biofilms, required for their survival.
Inflammation: Inflammation is a biological process present throughout the formation of acne lesions. C. acnes bacteria stimulate the production of pro-inflammatory mediators by several cell types of the pilosebaceous unit — keratinocytes, sebocytes and immune cells. This inflammatory phenomenon can be exacerbated by a variety of exogenous and endogenous factors such as hormones, stress and modifications in the composition of sebum.9
Anti-acne solutions available on the market often use combinations of active ingredients to target all of these factors. For example, zinc is used for anti-seborrhea; azelaic acid for its anti-inflammatory properties; piroctone olamine for antibacterial effects; and glycolic acid and salicylic acid for their keratolytic actions. In this context, a natural active was developed to target all four of these biological physiopathologies and restore homeostasis to acneic skin.
To this end, 39 raw materials were screened, including plants and microorganisms, of which pomegranate was found to have the highest antibacterial efficacy. Next, the optimal age and part of the pomegranate plant were identified by simultaneously monitoring metabolic tracers as well as antiseborrheic and antibacterial activities. Results showed the immature pericarp of pomegranate had the greatest molecular diversity and richness. It was therefore extracted to develop an anti-acne ingredient (INCI: Punica Granatum Pericarp Extract) whose efficacy was tested as described here using several in vitro models, including acne-mimicking reconstructed epidermis (RE),14 lymphocyte T helper 17 (LTh17) and sebocyte models, and phylotype IA1 C. acnes culture.
- Seité, S., et al. (2012 Oct). Enquête sur la prise en charge des patients acnéiques en France. Annales de Dermatologie et de Vénéréologie 139(10) 611 16; doi.org (crossref), https://doi.org/10.1016/j.annder.2012.06.039
- Dréno, B. (2015) Treatment of adult female acne: a new challenge. In : Journal of the European Academy of Dermatology and Venereology : JEADV, 29 Suppl 5, p. 14–19. DOI: 10.1111/jdv.13188.
- Dreno, B., et al. (2018 Oct). Female type of adult acne: Physiological and psychological considerations and management: Management of adult female acne. JDDG: Journal Der Deutschen Dermatologischen Gesellschaft 16(10) 1185 94; doi.org (crossref), https://doi.org/10.1111/ddg.13664
- Di Landro, A., et al. (2012 Dec). Family history, body mass index, selected dietary factors, menstrual history and risk of moderate to severe acne in adolescents and young adults. J Amer Acad Derm 67(6) 1129 35; doi.org (crossref), https://doi.org/10.1016/j.jaad.2012.02.018
- Clayton, R.W., et al. (2019 Oct). Homeostasis of the sebaceous gland and mechanisms of acne pathogenesis. Brit J Derm. 181(4) p 677-90; DOI.org (Crossref), https://doi.org/10.1111/bjd.17981
- Lee, W.J., et al. (2008 Jul). Influence of substance P on cultured sebocytes. Arch Derm Res. 300(6) p 311 16; DOI.org (Crossref), https://doi.org/10.1007/s00403-008-0854-1
- Rossiter, Heidemarie, et al. (2018 Oct). Inactivation of autophagy leads to changes in sebaceous gland morphology and function. Exper Derm. 27(10) p 1142 51; DOI.org (Crossref), https://doi.org/10.1111/exd.13752
- Zouboulis, C.C. (2009 Sep). Propionibacterium acnes and sebaceous lipogenesis: A love–hate relationship? JID. 129(9) p 2093 96; DOI.org (Crossref), https://doi.org/10.1038/jid.2009.190
- Bernales Salinas, A. (2021 Sep). Acne vulgaris: Role of the immune system. Intl J Derm 60(9) p 1076 81; DOI.org (Crossref), https://doi.org/10.1111/ijd.15415
- Zhang, N., et al. (2019 Dec). Antimicrobial susceptibility, biotypes and phylotypes of clinical Cutibacterium (formerly Propionibacterium) acnes strains isolated from acne patients: An observational study. Dermatology and Therapy. 9(4) p 735 46; DOI.org (Crossref), https://doi.org/10.1007/s13555-019-00320-7
- Saint-Jean, M., et al. (2019 Sep). Adult acne in women is not associated with a specific type of Cutibacterium acnes. J Amer Acad Derm. 81(3) p 851 52; DOI.org (Crossref), https://doi.org/10.1016/j.jaad.2019.03.040
- Paugam, C., et al. (2017 Sep). Propionibacterium acnes phylotypes and acne severity: An observational prospective study. J Eur Acad Derm Vener. 31(9) p e398 99; DOI.org (Crossref), https://doi.org/10.1111/jdv.14206
- Dagnelie, M.-A., Montassier, E., Khammari, A., Mounier, C., Corvec, S. and Dréno, B. (2019). Inflammatory skin is associated with changes in the skin microbiota composition on the back of severe acne patients. Exper Derm. 28(8) p 961–967; DOI: 10.1111/exd.13988
- Laclaverie, M., et al. (2021 Mar). Development and characterization of a 3D in vitro model mimicking acneic skin. Exper Derm 30(3) 347 57; doi.org (crossref), https://doi.org/10.1111/exd.14268