Jianxin Wu

Background: Glabridin, a natural compound derived from Glycyrrhiza glabra L., possesses skin-lightening effects. This study aims to further elucidate the depigmentation mechanism of glabridin by investigating its effects on melanogenesis and melanin transfer. Methods: We initially confirmed the anti-melanogenic effects of glabridin in MNT-1 human melanoma cells. Then, we investigated the mechanism of its anti-melanogenic effect by evaluating the protein expression of β-catenin and MITF via Western blot. To investigate melanin transfer, we compared glabridin’s efficacy with that of niacinamide, a recognized inhibitor of melanosome transfer and employed two complementary experimental models: (1) α-melanocyte-stimulating hormone (α-MSH)-stimulated MNT-1 cells to analyze dendrite formation, and (2) a UVB-irradiated co-culture system of MNT-1 cells and HaCaT keratinocytes to evaluate melanin transfer. Results: By measuring glabridin’s effects on melanin content, tyrosinase activity, and melanogenesis-related protein expression confirmed its inhibition of melanin synthesis. Further investigation demonstrated that glabridin suppresses melanogenesis by downregulating β-catenin and MITF, indicating inhibition of the Wnt/β-catenin pathway. Furthermore, in α-MSH-treated MNT-1 cells, both glabridin and niacinamide were found to suppress dendrite formation and elongation. In a UVB-exposed co-culture system, both glabridin and niacinamide inhibited melanin transfer to keratinocytes. Mechanistically, these effects were linked to the regulation of Rho GTPases (Rac1, RhoA, Cdc42) and suppression of F-actin reorganization. Conclusions: This study provides, for the first time, evidence that the skin-lightening effect of glabridin involves two complementary mechanisms: inhibition of melanogenesis through suppression of the Wnt/β-catenin pathway, and attenuation of both dendricity and melanin transfer via the influence of Rho family GTPases expression.

Phenylethanol glycosides (PhGs) constitute crucial bioactive compounds in Cistanche Herba. However, their bioavailability is notably low. Research indicates that intestinal flora can metabolize PhGs into small polyphenols, enhancing bioavailability and pharmacological activities. In this paper, for the first time, a single strain, Beauveria bassiana, was found to be effective in converting PhGs from the crude extract of Cistanche tubulosa into small molecule polyphenols like hydroxytyrosol (HT), decaffeoylacteoside (HT-rha-glu), and caffeic acid through fermentation. We assessed the impact of pre- and post-fermentation on Propionibacterium acnes (P. acnes)-induced acne related to a western diet through in vitro cellular experiments. Both pre- and post-fermentation exhibited efficacy in inhibiting inflammation, oxidative stress, and mitochondrial membrane damage in P. acnes-induced HaCaT. Moreover, post-fermentation, unlike pre-fermentation, displayed stronger and a dose-dependent reduction in insulin-stimulated lipid synthesis in sebaceous gland cells. To further understand the increased efficacy of fermentation in inhibiting lipid synthesis, we investigated HT-rha-glu, the predominant small molecules produced during fermentation. It was shown that the compound inhibited lipid synthesis by decreasing gene expression of SREBP-1 and PPARγ in sebaceous gland cells.

The abnormal barrier function of the stratum corneum is a significant characteristic of surface-active agent-induced inflammatory skin diseases, and its cause is closely related to the abnormal lipid components of the stratum corneum. Total saponins of Panax notoginseng (TSPN) have significant potential in improving inflammatory skin barrier function. This study aims to investigate the barrier repair efficacy of TSPN using the EpiKutis^® skin model and to explore the potential mechanisms through multi-omics analysis based on transcriptomics, proteomics, and lipid metabolomics. We found that TSPN could ameliorate Sodium dodecyl sulfate (SDS)-induced barrier impairment in the EpiKutis^® model, alleviating stratum corneum thickening and upregulating the expression of barrier-related proteins, e.g., Filaggrin, Involucrin, and Loricrin. Through an integrated multi-omics network, we identified seven key target proteins and screened six lipid metabolites, which are involved in lipid metabolism and exert barrier-repairing effects through five pathways. The result indicated that TSPN might repair the epidermal barrier by regulating the phosphatidylinositol 3 kinase (PI3K)-protein kinase B (AKT)-mediated proliferation pathway, Mitogen-activated protein kinase (MAPK)-mediated apoptotic pathways, sphingolipid synthesis, Calcium/calmodulin-dependent protein kinase II beta (CAMK2B)-mediated actin cytoskeleton regulation, and Inositol-trisphosphate 3-kinase B (ITPKB)-mediated phosphatidylinositol signaling system. Further study is needed to explore the mechanism of the molecular link between lipid abnormalities and skin barrier function.

Gardeniae Fructus (GF), a traditional Chinese medicine rich in iridoids, has demonstrated skin-improving effects. However, its mechanisms for enhancing epidermal barrier function remain unclear. In this study, the iridoids in GF were characterized using UPLC-MS/MS. The improvement in the barrier function by GF was assessed through in vitro experiments and a human efficacy assessment. In addition, the potential targets were predicted through proteomics analysis, molecular docking, and molecular dynamics (MD), and verified in HaCaT cells and three-dimensional epidermal models. Nine iridoids were identified in GF. In vitro, GF effectively promoted cell migration and reduced cell damage and oxidative stress. Proteomics analysis combined with molecular docking and MD simulations predicted that the primary iridoids in GF ameliorate barrier function by binding to the aryl hydrocarbon receptor (AHR) with high affinity and stability. Subsequent validation demonstrated that GF significantly upregulated AHR, filaggrin (FLG), loricrin (LOR), and involucrin (IVL) mRNA and protein expression. A 28-day randomized double-blind human efficacy assessment in subjects with sensitive skin showed that the gel with GF increased stratum corneum hydration, reduced transepidermal water loss (TEWL), and lowered erythema index and lactic acid tingling. These findings suggest that GF enhances the skin barrier via AHR activation-mediated upregulation of barrier proteins, supporting its cosmeceutical potential.

Background: Sensitive skin exhibits impaired skin barrier function. The lipid composition of the skin, a pivotal element within the stratum corneum’s “brick-and-mortar” structure, plays a dual role: it is integral to cell differentiation processes and serves as a vital nutrient reservoir for cutaneous microbiota, thereby influencing the skin’s microecological balance. There is a notable research gap concerning the comparative analysis of physiological parameters and lipid profiles among individuals with sensitive dry skin (SDS), sensitive oily skin (SOS), and healthy skin (HS). Methods: A total of 95 females (18–25 years) were grouped: SDS (n = 32), SOS (n = 31), and HS (n = 32). Stratum corneum water content, oil content, and TEWL were measured. Lipids from sebaceous glands and stratum corneum (tape-stripping) underwent UPLC-QTOF-MS analysis. Differential lipids were identified via OPLS-DA, volcano plots, and LMSD. Results: In terms of physiological indicators, notable disparities emerged in oil content and stratum corneum water content between the SOS and both the HS and the SDS. Sensitive skin, whether dry or oily, displayed a higher transepidermal water loss (TEWL) value than healthy skin, reflecting a declined state of skin barrier function. Regarding the sebum samples, the relative percentages of sphingolipids (SP) and glycerophospholipids (GP) were significantly higher in SDS. Regarding the stratum corneum samples, the percentages of SP in SDS were significantly higher. Conclusions: This study, for the first time, conducted a comprehensive analysis of the skin’s physiological properties, lipidomics of sebum, and stratum corneum lipids among groups with SDS, SOS, and HS. These observations indicate a profound association between skin barrier dysfunction in SDS individuals and, in particular, sphingolipids (SP).

Gardeniae Fructus (GF), the desiccative mature fruitage of Gardenia jasminoides J. Ellis (G. jasminoides), is a traditional herbal medicine in China with potential value against skin photodamage. However, the phytochemical basis and mechanisms underlying GF’s anti-photodamage effects remain unclear. In this study, the chemical components in GF extract (GFE) were analyzed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS), and iridoids were identified as the main components. The antioxidant, anti-inflammatory, and barrier-repair effects of GFE in UVB-induced photodamage were assessed through in vitro experiments. Additionally, the potential mechanisms of GFE against skin photodamage were predicted using proteomics and network pharmacology. The results showed that GFE significantly increased the levels of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) induced by UVB, while decreasing reactive oxygen species (ROS) and malondialdehyde (MDA) contents. GFE also inhibited the secretion of interleukin-6 (IL-6) and interleukin-1β (IL-1β). Additionally, GFE upregulated the expression of filaggrin (FLG), loricrin (LOR), and involucrin (IVL) in 3D epidermal skin models. Proteomic analysis and network pharmacology indicated that the iridoid components identified in GFE ameliorated UVB-induced damage probably by regulating cell cycle-related proteins and signaling pathways, though this requires further experimental confirmation. Overall, the results provide essential evidence to support the development of GFE as a skincare active ingredient.

Skin microecology involves a dynamic equilibrium among the host, microbiome, and internal/external environments. This equilibrium, shaped by multifactorial interactions, reflects individual specificity and diversity. Creating a replicable in vitro skin microecological model is highly challenging. Here, we introduce a mimicked stratum corneum microecology model (SCmic). It uses light cured crosslinked hydrogels as a scaffold and moisture source, and nonviable epidermal cells as the main nutrient. This setup establishes a suitable, stable, and reproducible microecology for microbiome colonization. Notably, it replicates the normal/oily skin microbiota with no significant differences from the original native microbiota at the genus level. Simultaneously, we have developed a standardized human skin microbiota model (Hcm), featuring seven dominant strains that form a representative microbial community. The models provide highly convenient approaches for exploring the intricate mutual interactions among skin microecology, influence of microbiota on skin health, and metabolism of chemical substances by microbiota.

Glycation is a process in which reducing sugars bind to proteins, resulting in the formation of advanced glycation end products (AGEs). These AGEs accumulate in the skin, promote excessive collagen crosslinking, and disrupt the extracellular matrix (ECM), impairing normal cellular functions and contributing to skin aging. To evaluate the anti-glycation efficacy of lotus stamen extract (LSE), we employed the BSA–fructose system and a high glucose (HG)-induced fibroblast glycation model. The results demonstrated that LSE effectively inhibited cellular glycation and also exhibited anti-inflammatory, antioxidative, and anti-senescent effects in HG-induced human skin fibroblasts (HSF). Further investigation into the anti-glycation mechanism and component analysis of the lotus stamen ethyl acetate extract (LSEE) led to the identification of 15 flavonoids. The anti-glycation results indicated that these flavonoids are likely the primary active constituents in LSE. Mechanistic studies revealed that GLO1 plays a crucial role in cellular resistance to glycation, and LSEE enhanced GLO1 expression through the Nrf2/Keap1 pro-survival pathway, thereby mitigating intracellular AGE production. In summary, LSEE and its multiple flavonoid components exhibit potent intracellular anti-glycation activity and present significant potential to be developed as a natural and organic product for cosmetic and healthcare applications.