Morgane De Tollenaere

Recent evidence suggests that microbiota-derived porphyrins contribute to skin aging, a phenomenon termed porphyr’aging. These pro-inflammatory molecules alter the expression of genes involved in senescence, trigger melanogenesis, and decrease collagen I synthesis in skin. The aim of this study was to evaluate the anti-aging properties of an upcycled Laminaria hyperborea extract (LHE) targeting bacterial porphyrins discovered after screening. The impact of LHE on porphyrin biosynthesis and on melanogenesis and wrinkles was evaluated using in vitro and ex vivo tests and by conducting a double-blinded vs. placebo clinical trial. LHE significantly reduced coproporphyrin III production in Gram-positive skin bacteria and significantly decreased porphyrin levels in vivo at the skin surface. This activity was supported by a specific composition of LHE, comprising laminaran and mannitol. It also significantly decreased melanin content in skin explants and pigmentation in the clinical study (−5.9%). This effect was particularly pronounced in dark spots (ITA +39.9%), and the number of precursor spots also decreased (−6.9%). In addition, LHE significantly stimulated type I α-1 pro-collagen production in fibroblasts and increased collagen I and elastin expression in skin explants. These results were consistent with the clinical study, showing significant reductions in wrinkle number (−9.8%) and area (−5.8%). These findings suggest that targeting microbiota-derived porphyrins and their consequences may represent a promising approach to reduce the visible signs of aging.

(1) Background: Low-molecular-weight hyaluronic acid displays moisturizing and anti-aging properties and reduces UV-induced inflammation when applied topically. A 3 kDa sodium hyaluronate oligosaccharide (Extra-Low HA) was designed, and studies were performed to evaluate its safety for cosmetic applications. (2) Methods: The ability of the Extra-Low HA (ExLMW-HA) to penetrate skin was evaluated. Then, pro-inflammatory cytokines were quantified in the culture medium of skin explants following ExLMW-HA application with or without inflammation inducer (PMA). Finally, four predictive in vitro tests (Keratinosens^™, kDPRA, Ames’ test, micronucleus test) were conducted to assess the safety of ExLMW-HA. (3) Results: The molecule permeates skin down to the living epidermis and possibly interacts with the dermal compartment. The oligosaccharide did not induce TNF-α, IL-1β, IL-1α, CXCL2, CCL3, or IL-15, neither in basal nor in stressed conditions. ExLMW-HA is not predicted to be a skin sensitizer or a mutagenic or genotoxic substance. (4) Conclusions: This 3 kDA HA is considered safe for use in topical application at the tested dosage.

Benefit/risk management of skin exposure to sunlight, especially ultraviolet (UV) rays, is mainly driven by photoaging, cancer incidence, and the requirement for vitamin D3 synthesis. Antioxidant phytocompounds are considered to be a valuable source of molecules to protect skin from UV-induced damage, but their impact on other UV-related metabolic pathways is rarely described. In this study, an indigoid-rich Persicaria tinctoria extract (PTE) was evaluated on three consequences of UV exposure: DNA damage and inflammation, vitamin D3 content, and melanogenesis. A moderate UV exposure was applied on skin models, corresponding to approximately 1 h exposure in the spring in western Europe. UV-induced DNA damage and inflammation were measured through the quantification of cyclobutane pyrimidine dimers (CPDs) and cytokines. Response to heat stress was quantified through the release of prostaglandin. Then, the impact of PTE on vitamin D3 and melanin synthesis was observed. PTE decreased by −56% in the number of cells presenting CPDs. PTE decreased the production of pro-inflammatory cytokine IL-6 (−59%) and stimulated the release of the protective cytokine IL-1Ra (+49%). It decreased PGE₂ release by −27%. In skin explants, PTE boosted the vitamin D3 concentration (+345%). Several genes involved in melanogenesis were up-regulated by PTE (MC1R × 2.46, MITF × 1.69, TYR × 2.06, MLPH × 1.53). It promoted melanin content by +126% and by +86% when associated with SPF 30. The extract decreased the amount of protective eumelanin, leading to visible skin tanning of reconstructed human epidermis (L*-15%, ITA −125%). As a new finding, PTE minimized DNA damage and inflammation caused by a daily dose of UV, and surprisingly, promoted vitamin D3 and eumelanin synthesis, suggesting that it represents an opportunity to reconcile skin protection and the physiological need for sunlight.

Objective: Porphyrins are ubiquitous metabolites and are constitutive of the bacterial metabolome of healthy skin. Their consideration has until now been limited to their pro‐inflammatory activity in acne vulgaris . The present work suggests a new role for these molecules in the onset of skin ageing. Methods: A mixture of coproporphyrin III and protoporphyrin IX, representative of skin microbiota metabolites, was defined and applied in different skin models. Finally, an in vivo study was conducted to determine the association between porphyrin's abundance and ageing signs. Results: Bacterial porphyrins penetrated stratum corneum and reached living epidermal cells. The porphyrin mixture increased IL‐8, ROS and melanin contents. Porphyrin‐induced melanin synthesis appeared to be regulated by translocator protein TSPO/PBR. In fibroblasts, bacterial metabolites down‐regulated a set of transcripts involved in extracellular matrix architecture and associated with ageing, which was confirmed by a decrease of type I pro‐collagen. Finally, the clinical study established positive and significant correlations between porphyrin abundance and the severity of ageing signs, including invisible spots, brown spots and wrinkles length. Conclusion: In summary, porphyrins could play unexpected roles in skin's premature ageing process, a phenomenon we propose to call Porphyr'ageing, that promotes hyperpigmentation, inflammation, oxidative stress and fibroblast cell ageing, leading to dermal matrix weakening.

Cranberry oil is known for nutritional benefits, and this work is aimed at studying its soothing properties and potential as an intimate care ingredient. The antioxidant, anti-inflammatory, and anti-irritation properties of cranberry oil were evaluated on epithelial cells and tissues, including the vaginal epithelium. The impact of the oil on vaginal microbiota was assessed in vitro. Cranberry oil reduced oxidative stress in keratinocytes (ROS −43%) and lowered inflammation by lessening the release of cytokines IL-8 (−33%) and TNF-α (−32%). Irritation induced by sodium dodecyl sulfate (SDS) in skin explants was lowered by 24%. Cranberry oil and fruit extract acted synergistically on inflammation, decreasing TNF-α release by 75% (vs. −34% and −16%, respectively). Cranberry oil reduced inflammation on EpiVaginal™ tissue, decreasing IL-6 by 36%. The minimum inhibitory concentration (MIC) of cranberry oil on the pathogenic vaginal microorganisms C. albicans and G. vaginalis was 0.5% and 0.1%, respectively. The oil promoted the growth of commensal L. jensenii (×79 at 0.1%) and favored a high proportion of lactic acid bacteria when co-cultured with C. albicans. Cranberry oil has antioxidant, anti-inflammatory, and soothing properties on skin. Anti-inflammatory activity was confirmed on vaginal epithelium, and initial in vitro evidence indicates that the oil can balance vaginal flora to prevent dysbiosis.

Background: Conspicuous facial pores are benign but represent a cosmetic concern for men and women. Recent works described dermal and epidermal impairments as clinical causes of enlarged pores. Morphological modifications of skin at the site of pores were associated with collagen density loss, possible alteration of extracellular matrix and abnormal differentiation of keratinocytes.Aims: A composition containing mannose‐6‐phosphate (Active Complex) was designed to address these different aspects of pore enlargement. In vitro and ex vivo evaluations were conducted in different models mimicking disturbance of dermal and epidermal functions. The pore refining activity of Active Complex was assessed in two clinical trials studying a Caucasian women cohort and an Asian men cohort.Results: At the dermal level, Active Complex upregulated collagen I and decorin synthesis, and genes encoding collagens I, III, V, VII, XVII; suggesting its ability to favor collagen fiber organization and anchorage. The downregulation of matrix metalloprotease, involved in extracellular matrix degradation, reinforced the protective effect of Active Complex in the dermis. Active Complex down modulated differentiation markers in keratinocytes as well as genes involved in cell renewal. Study of reconstructed human epidermis modeling keratinocyte hyperproliferation revealed that Active Complex mitigated two markers of this state: number of nuclei in the stratum corneum and involucrin expression. Clinical trials confirmed the pore refining activity of Active Complex on men and women of different ages and ethnicities; −24% total skin pore area after 56 days of application on women, and −30.2% on men after 7 days.Conclusions: This work demonstrates the interest to target dermal and epidermal modifications described in conspicuous pore area, especially dermis fiber organization, to address this cosmetic concern.

Freesia refracta (FR), a perennial flower of the Iris family (Iridaceae), is widely used in cosmetics despite limited scientific evidence of its skin benefits and chemical composition, particularly of FR callus extract (FCE). This study identified biologically active compounds in FCE and assessed their skin benefits, focusing on anti-aging. FR calli were cultured, extracted with water at 40 °C, and analyzed using Centrifugal Partition Chromatography (CPC), Nuclear Magnetic Resonance (NMR), and HCA, revealing key compounds, namely nicotinamide and pyroglutamic acid. FCE significantly increased collagen I production by 52% in normal and aged fibroblasts and enhanced fibroblast–collagen interaction by 37%. An in vivo study of 43 female volunteers demonstrated an 11.1% reduction in skin roughness and a 2.3-fold increase in collagen density after 28 days of cream application containing 3% FCE. Additionally, the preservation tests of cosmetics containing FCE confirmed their stability over 12 weeks. These results suggest that FCE offers substantial anti-aging benefits by enhancing collagen production and fibroblast–collagen interactions. These findings highlighted the potential of FCE in cosmetic applications, providing significant improvements in skin smoothness and overall appearance. This study fills a gap in the scientific literature regarding the skin benefits and chemical composition of FR callus extract, supporting its use in the development of effective cosmeceuticals.

Background: Hyaluronic acid (HA) is a widely used active cosmetic ingredient. Its multiple skin care benefits are modulated by its molecular weight. Low molecular weight (LMW) HA can penetrate the skin, but high molecular weight (HMW) HA remains at the surface. Here, we assessed how vectorization of HMW HA with bentonite clay—achieved with an innovative technology—enhances its cosmetic and hydrating properties. Materials and Methods: The two HA forms were applied to skin explants; their penetration and smoothing effects were monitored by Raman spectroscopy and scanning electron microscopy. The two forms were biochemically characterised by chromatography, enzyme sensitivity assays, and analysis of Zeta potential. Cosmetics benefits such as, the smoothing effect of vectorised‐HA was assessed in ex vivo experiments on skin explants. A placebo‐controlled clinical study was finally conducted applying treatments for 28 days to analyse the final benefits in crow's feet area. Results: Raman spectroscopy analysis revealed native HMW HA to accumulate at the surface of skin explants, whereas vectorised HMW HA was detected in deeper skin layers. This innovative vectorisation process changed the zeta potential of vectorised HMW HA, being then more anionic and negative without impacting the biochemical structure of native HA. In terms of cosmetic benefits, following application of vectorised HMW HA ex vivo , the skin's surface was visibly smoother. This smoothing was clinically confirmed, with a significant reduction in fine lines. Conclusion: The development of innovative process vectorising HMW HA allowed HMW HA penetration in the skin. This enhanced penetration extends the clinical benefits of this iconic cosmetic ingredient.

Background: The COVID‐19 pandemic brought about a new normal, necessitating the use of personal protective equipment (PPE) like face shields, surgical masks, gloves, and goggles. However, prolonged mask‐wearing introduced skin‐related issues due to changes in the skin's microenvironment, including increased humidity and temperature, as well as pressure on the skin. These factors led to skin deformation, vascular issues, edema, and inflammation, resulting in discomfort and cosmetic concerns. Clinical reports quickly highlighted the consequences of long‐term mask use, including increased cases of “maskne” (mask‐related acne) or mask‐wearing related disorders such as rosacea flare‐ups, skin‐barrier defects, itching, erythema, redness, hyperpigmentation, and lichenification. Some of these issues, like inflammation, oxidative stress, and poor wound healing, could be directly linked to acne‐related disorders or skin hypoxia. Aim: To address these problems, researchers turned to rutin, a well‐known flavonoid with antioxidant, vasoactive, and anti‐inflammatory properties. However, rutin's poor water solubility presented a challenge for cosmetic formulations. To overcome this limitation, a highly water‐soluble form of rutin was developed, making it suitable for use at higher concentrations. Methods: In vitro and ex vivo tests were conducted, as well as an innovative clinical trial including volunteers wearing surgical masks for at least 2 h, to evaluate the biological activity of this soluble rutin on the main skin concerns associated with mask‐wearing (inflammation, oxidative stress, skin repair, hyperpigmentation, and skin redness). Results: The in vitro results showed that the active ingredient significantly reduced oxidative stress, improved wound healing, and reduced inflammation. In dark skin explants, the active ingredient significantly reduced melanin content, indicating its lightening activity. This effect was confirmed in the clinical study, where brown spots decreased significantly after 4 days of application. Moreover, measurements on volunteers demonstrated a decrease in skin redness and vascularization after the active ingredient application, indicating inflammation and erythema reduction. Volunteers reported improved skin comfort. Conclusion: In summary, the COVID‐19 pandemic led to various skin issues associated with mask‐wearing. A highly soluble form of rutin was developed, which effectively addressed these concerns by reducing inflammation, oxidative stress, and hyperpigmentation while promoting wound healing. This soluble rutin offers a promising solution for the rapid treatment of maskne‐related disorders and other skin problems caused by prolonged mask use.

Digital stress is a newly identified cosmetic stress that is mainly characterized by blue light exposure. The effects of this stress have become increasingly important with the emergence of personal digital devices, and its deleterious effects on the body are now well-known. Blue light has been observed to cause perturbation of the natural melatonin cycle and skin damage similar to that from UVA exposure, thus leading to premature aging. “A melatonin-like ingredient” was discovered in the extract of Gardenia jasminoides, which acts as a filter against blue light and as a melatonin-like ingredient to prevent and stop premature aging. The extract showed significant protective effects on the mitochondrial network of primary fibroblasts, a significant decrease of −86% in oxidized proteins on skin explants, and preservation of the natural melatonin cycle in the co-cultures of sensory neurons and keratinocytes. Upon analysis using in silico methods, only the crocetin form, released through skin microbiota activation, was found to act as a melatonin-like molecule by interacting with the MT1-receptor, thus confirming its melatonin-like properties. Finally, clinical studies revealed a significant decrease in wrinkle number of −21% in comparison to the placebo. The extract showed strong protection against blue light damage and the prevention of premature aging through its melatonin-like properties.