Human skin acts as a barrier to protect our bodies from UV rays and external pathogens and to prevent water loss. Phenotypes of aging, or natural aging due to chronic damage, include wrinkles and the reduction of skin thickness that occur because of a loss of skin cell function. The dysregulation of autophagy, a lysosome-related degradation pathway, can lead to cell senescence, cancer, and various human diseases due to abnormal cellular homeostasis. Here, we discuss the roles and molecular mechanisms of autophagy involved in the anti-aging effects of autophagy and the relationship between autophagy and aging in skin cells.

Melanogenesis is the sequential process of melanin production by melanocytes in order to protect the skin from harmful stimuli. Melanogenesis is disrupted by radiation exposure, which results in the differentiation of melanocytes into melanoma. Recently, some methods have been developed to maintain the instability of melanogenesis in melanoma by activating cellular autophagy. However, there is still a lack of knowledge about how autophagy is involved in the regulation of melanogenesis in melanoma cells. Here, we used rottlerin as an autophagy inducer to investigate the role of the cyclic adenosine monophosphate (cAMP)/cAMP response element binding (CREB) signaling pathway in melanogenesis. We found that rottlerin can inhibit melanin production by targeting cAMP, which is initially activated by alpha-melanocyte stimulating hormone (α-MSH). Our findings suggest that rottlerin has a pivotal role as an autophagy inducer in the regulation of melanogenesis by targeting the cAMP/CREB signaling pathway.

Autophagy is the sequential process whereby cell components are degraded, which can occur due to nutrient deprivation. Its regulation has an essential role in many diseases, functioning in both cell survival and cell death. Autophagy starts when mTORC1 is inhibited, resulting in the activation of several complexes to form a cargo that fuses with a lysosome, where it undergoes degradation. In this review, we describe a plant extract that is well known in Korea, namely Korean ginseng extract; we studied how its derivatives and metabolites can regulate autophagy and thus mediate the pathogenesis of certain diseases.

Piper cubeba L. is a plant in the Piperaceae family that is generally found in tropical countries and acts as an antioxidant and anti-inflammatory agent. Unfortunately, the molecular mechanism of the anti-inflammatory activity has not been fully investigated. In this study, we elucidated the anti-inflammatory mechanism by focusing on NF-κB signaling, which is considered a prototypical inflammatory signaling pathway in both innate and adaptive immune functions. Cellular activity and the molecular target of Pc-ME were identified in macrophage RAW264.7 cells and HEK293T cells by assessing NO production, cytokine expression by RT-PCR, luciferase gene reporter assay, and protein regulation in cytoplasm by Western blot upon NF-κB activation. Pc-ME reduced NO production without any cell toxicity; inhibited expression of proinflammatory cytokines such as iNOS and IL-6; downregulated NF-κB activation mediated by both MyD88 and TRIF; and diminished the phosphorylation of IκBα, IKKα/β, Akt, p85, Src, and Syk. Pc-ME inhibited Syk and Src autophosphorylation during overexpression in HEK cells, which confirmed our hypothesis that Syk and Src were signaling targets of Pc-ME. These findings indicate that Piper cubeba L. has anti-inflammatory activity by targeting Src/Syk in the NF-κB pathway.

The Licania genus has been used in the treatment of dysentery, diabetes, inflammation, and diarrhea in South America. Of these plants, the strong anti-inflammatory activity of Licania macrocarpa Cuatrec (Chrysobalanaceae) has been reported previously. However, the beneficial activities of this plant on skin health have remained unclear. This study explores the protective activity of a methanol extract (50–100 μg/mL) in the aerial parts of L. macrocarpa Cuatrec (Lm-ME) and its mechanism, in terms of its moisturizing/hydration factors, skin wrinkles, UV radiation-induced cell damage, and radical generation (using RT/real-time PCR, carbazole assays, flowcytometry, DPPH/ABTS, and immunoblotting analysis). The anti-pigmentation role of Lm-ME was also tested by measuring levels of melanin, melanogenesis-related genes, and pigmentation-regulatory proteins. Lm-ME decreased UVB-irradiated death in HaCaT cells by suppressing apoptosis and inhibited matrix metalloproteinases 1/2 (MMP1/2) expression by enhancing the activity of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. It was confirmed that Lm-ME displayed strong antioxidative activity. Lm-ME upregulated the expression of hyaluronan synthases-2/3 (HAS-2/3) and transglutaminase-1 (TGM-1), as well as secreted levels of hyaluronic acid (HA) via p38 and JNK activation. This extract also significantly inhibited the production of hyaluronidase (Hyal)-1, -2, and -4. Lm-ME reduced the melanin expression of microphthalmia-associated transcription factor (MITF), tyrosinase, and tyrosinase-related protein-1/2 (TYRP-1/2) in α-melanocyte-stimulating hormone (α-MSH)-treated B16F10 cells via the reduction of cAMP response element-binding protein (CREB) and p38 activation. These results suggest that Lm-ME plays a role in skin protection through antioxidative, moisturizing, cytoprotective, and skin-lightening properties, and may become a new and promising cosmetic product beneficial for the skin.