Our skin is an organ with the largest contact area between the human body and the external environment. Skin aging is affected directly by both endogenous factors and exogenous factors (e.g., UV exposure). Skin saccharification, a non-enzymatic reaction between proteins, e.g., dermal collagen and naturally occurring reducing sugars, is one of the basic root causes of endogenous skin aging. During the reaction, a series of complicated glycation products produced at different reaction stages and pathways are usually collectively referred to as advanced glycation end products (AGEs). AGEs cause cellular dysfunction through the modification of intracellular molecules and accumulate in tissues with aging. AGEs are also associated with a variety of age-related diseases, such as diabetes, cardiovascular disease, renal failure (uremia), and Alzheimer’s disease. AGEs accumulate in the skin with age and are amplified through exogenous factors, e.g., ultraviolet radiation, resulting in wrinkles, loss of elasticity, dull yellowing, and other skin problems. This article focuses on the damage mechanism of glucose and its glycation products on the skin by summarizing the biochemical characteristics, compositions, as well as processes of the production and elimination of AGEs. One of the important parts of this article would be to summarize the current AGEs inhibitors to gain insight into the anti-glycation mechanism of the skin and the development of promising natural products with anti-glycation effects.

Pearl powder is a famous traditional Chinese medicine that has a long history in treating palpitations, insomnia, convulsions, epilepsy, ulcers, and skin lightining. Recently, several studies have demonstrated the effects of pearl extracts on protection of ultraviolet A (UVA) induced irritation on human skin fibroblasts and inhibition of melanin genesis on B16F10 mouse melanoma cells. To further explore the effect we focused on the whitening efficacy of pearl hydrolyzed conchiolin protein (HCP) on human melanoma MNT-1 cells under the irritation of alpha-melanocyte-stimulating hormone (α-MSH) or endothelin 1 (ET-1) to evaluate the intracellular tyrosinase and melanin contents, as well as the expression levels of tyrosinase (TYR), tyrosinase related protein 1 (TRP-1), and dopachrome tautomerase (DCT) genes and related proteins. We found that HCP could decrease the intracellular melanin content by reducing the activity of intracellular tyrosinase and inhibiting the expression of TYR, TRP-1, DCT genes and proteins. At the same time, the effect of HCP on melanosome transfer effect was also investigated in the co-culture system of immortalized human keratinocyte HaCaT cells with MNT-1. The result indicated that HCP could promote the transfer of melanosomes in MNT-1 melanocytes to HaCaT cells, which might accelerate the skin whitening process by quickly transferring and metabolizing melanosomes during keratinocyte differentiation. Further study is needed to explore the mechanism of melanosome transfer with depigmentation.

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.

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).

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.

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.