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Introduction: Peroxisome proliferator-activated receptor (PPAR) agonists are known to modulate the synthesis of dermal lipids and proteins including collagens. Olive (Olea europaea) leaves have been reported to contain PPAR-binding ligands. Collagen IV, a major dermal-epidermal junction (DEJ) protein, degrades with both age and disease. Here, we report the formulation of a novel multi-ligand complex, Linefade, and its effects on collagen IV synthesis., Methods: Linefade prepared from the leaves of Olea europaea contains 2% w/w plant extract solids dissolved in a mixture of glyceryl monoricinoleate and dimethyl isosorbide. In silico docking was performed with PPAR-α (PDB ID: 2P54). Linefade was evaluated for PPAR-α-dependent transcription in a luciferase reporter assay system. Cell viability and collagen IV levels in human dermal fibroblast cultures were measured using the MTT method and ELISA assay, respectively. Transcriptome analysis was conducted on a full-thickness reconstituted human skin (EpiDermFT) model. Ex vivo cell viability and collagen IV immunostaining were performed on human skin explants., Results: In silico docking model of the major constituents (oleanolic acid and glyceryl monoricinoleate) produced a co-binding affinity of -6.7 Kcal/mole. Linefade significantly increased PPAR-α transcriptional activity in CHO cells and collagen IV synthesis in adult human dermal fibroblasts. Transcriptome analysis revealed that 1% Linefade modulated the expression of 280 genes with some related to epidermal differentiation, DEJ, PPAR, Nrf2 and retinoid pathways. An ex vivo human explant study showed that 1% Linefade, delivered via a triglycerides excipient, increased collagen IV levels along the dermal-epidermal junction by 52%., Conclusion: In silico modelling and in vitro and ex vivo analyses confirmed Linefade-mediated activation of PPAR-α and stimulation of collagen IV synthesis., (© 2021 Contrast Product Development, LLC. International Journal of Cosmetic Science published by John Wiley & Sons Ltd on behalf of Society of Cosmetic Scientists and Societe Francaise de Cosmetologie.)

Background: Terminalia chebula (TC) is a deciduous tree of which extracts have demonstrated efficacy for treatment of photodamage, skin aging, and wound healing. However, molecular and cellular mechanisms underlying these benefits remain unclear., Objective: To profile dermal expression responses to a standardized tannin-enriched TC fruit extract (Synastol ® TC)., Materials and Methods: Microarrays were used to evaluate gene expression in three-dimensional reconstituted human skin cultures., Results: Genome-wide expression responses to TC were the opposite to those observed in cells exposed to oxidative stress, solar-simulated UV radiation, and wounding, with increased expression of genes associated with water homeostasis, skin barrier establishment, blood vessel development, and circadian rhythms. TC also increased expression of extracellular matrix components, such as collagens (COL1A1, COL1A2) and proteoglycans (PRELP, OGN), and in separate assays, we showed that TC inhibits MMP enzymes (MMP-1, MMP-2, MMP-3, MMP-9, MMP-12) and microbial activity (S. aureus, P. acnes). Unexpectedly, mRNA and protein levels of late keratinocyte (KC) differentiation markers (FLG, LOR) were increased by TC, and expression responses in skin cultures broadly resembled those that occur with KC differentiation. Consistent with these results, TC increased expression of transcription factors regulating KC differentiation (FOS, GHRL3, PPARG) and we noted enrichment of AP-1 binding sites in regions upstream of TC-increased genes., Conclusion: These results demonstrate that functionally important TC extract responses occur in the epidermis and are therefore not restricted to the dermal layer. Our findings thus suggest mechanisms by which TC may strengthen full-thickness skin architecture for treatment of skin aging and/or chronic wounds.

Objective: The study was undertaken to compare the skin care related activities of retinol and bakuchiol, a potential alternative to retinoids. Retinol is a pivotal regulator of differentiation and growth of developing as well as adult skin. Retinoic acid is the major physiologically active metabolite of retinol regulating gene expression through retinoic acid receptor - dependant and independent pathways., Methods: Comparative gene expression profiling of both substances in the EpiDerm FT full thickness skin substitute model was undertaken. Furthermore, type I, III and IV collagen, as well as aquaporin 3 expression was analyzed by ELISA and/or histochemistry in human dermal fibroblasts and/or Epiderm FT skin substitutes., Results: Bakuchiol is a meroterpene phenol abundant in seeds and leaves of the plant Psoralea corylifolia. We present evidence that bakuchiol, having no structural resemblance to retinoids, can function as a functional analogue of retinol. Volcano plots showed great overall similarity of retinol and bakuchiol effects on the gene expression profile. This similarity was confirmed by the side-by-side comparison of the modulation of individual genes, as well as on the protein level by ELISA and histochemistry. Retinol-like functionality was further confirmed for the upregulation of types I and IV collagen in DNA microarray study and also show stimulation of type III collagen in the mature fibroblast model. Bakuchiol was also formulated into a finished skin care product and was tested in clinical case study by twice-a-day facial application. The results showed that, after 12 weeks treatment, significant improvement in lines and wrinkles, pigmentation, elasticity, firmness and overall reduction in photo-damage was observed, without usual retinol therapy-associated undesirable effects., Conclusion: Based on these data, we propose that bakuchiol can function as an anti-ageing compound through retinol-like regulation of gene expression., (© 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Objective: Skin compartments traditionally targeted by cosmetic actives - epidermis and dermis - are anchored and nourished by the underlying hypodermis, which therefore should be a key target for skin-rejuvenating formulations. However, given the difficulty to reach even the superficial layers of the skin, and to its 'unglamorous' fatty composition, the regenerative potential of hypodermis remains largely untapped. Therefore, this study was to investigate the capacity of a cosmetic material to trigger a regenerative response in dermis and epidermis through a selective action on hypodermis. Furthermore, it aimed to establish the effect of such cosmetic material in transbuccal hypodermal delivery form, on the hypodermal precursor cells - the preadipocytes., Methods: A combination of grape seed extract and soy phospholipids was formulated and standardized for elastase activity and free radical inhibition. This formulation was then used to contact the hypodermal layer of human skin biopsies and - under a transbuccal delivery vehicle form - the 3T3-L1 preadipocytes, and its effects were quantified using PCR arrays and histochemistry., Results: Application of the standardized grape/soy material to the hypodermal layer of skin triggered modulation of gene expression in the upper layers of the skin and resulted in the clear morphological improvement at the dermal and epidermal levels. Furthermore, when this material was formulated in a mucoadhesive, intraoral film and applied on 3T3-L1 preadipocytes, the resulting modulation of gene expression in these cells was consistent with differentiation and detoxification effects., Conclusions: These results suggest that transbuccal formulations of nutraceutical grade cosmetics have potential to induce signal transduction pathways in facial hypodermis, resulting in anti-aging effects throughout all skin compartments, including dermal and epidermal layers., (© 2013 Society of Cosmetic Scientists and the Société Française de Cosmétologie.)

Lycium barbarum L. (Solanaceae) glycoconjugates (LbGp) display an interesting array of anti-apoptotic and antioxidant properties, which may be beneficial for human skin. We therefore set out to determine the effects of LbGp in full-thickness human skin, and in dermal fibroblasts. It was found that LbGp decreased the level of MMP (matrix metalloproteinase)-1 significantly, but not that of MMP-3 or -13, in the whole human skin system, without compromising the viability of the skin. Consistently, LbGp inhibited skin expansion under mechanical stress, which in this model depends on the activity of MMP-1. We found that one of L. barbarum glycoconjugates, the LbGp5, promoted the survival of human fibroblasts cultured in suboptimal conditions. Furthermore, in the presence of LbGp5, these cultures also contained higher levels of the MMP-1 substrate--collagen type I. Together these results suggest that L. barbarum glycoconjugates in general, and LbGp5 in particular, may have important skin-protective properties.