Anti-inflammatory, Antioxidative, and Moisturizing Effects of Oxyceros horridus Lour. Ethanol Extract in Human Keratinocytes via the p38 Signaling Pathway.

Skin is the largest and outermost organ in the human body; it serves as a vital defense mechanism against various external threats. Therefore, it is crucial to maintain its health through protection against harmful substances and adequate moisture levels. This study investigates the anti-inflammatory, antioxidant, and moisturizing properties of Oxyceros horridus Lour. (Oh-EE) in human keratinocytes. Oh-EE demonstrates potent antioxidant activity and effectively protects against oxidative stress induced by external stimuli such as UVB radiation and H2O2. Additionally, it exhibits significant anti-inflammatory effects proven by its ability to downregulate the expression of pro-inflammatory cytokines, namely COX-2 and IL-6. The study also explores the involvement of the AP-1 pathway, highlighting the ability of Oh-EE to suppress the expression of p38 and its upstream regulator, MKK3/6, under UVB-induced conditions. Interestingly, Oh-EE can activate the AP-1 pathway in the absence of external triggers. Furthermore, Oh-EE enhances skin moisture by upregulating the expression of key genes involved in skin hydration, namely HAS3 and FLG. These findings underscore the potential of Oh-EE as a versatile ingredient in skincare formulations, providing a range of skin benefits. Further research is warranted to comprehensively understand the underlying mechanisms through which Oh-EE exerts its effects.

Anti-oxidative, anti-apoptotic, and anti-inflammatory activities of Connarus semidecandrus Jack ethanol extract in UVB-irradiated human keratinocytes.

ETHNOPHARMACOLOGICAL RELEVANCE: Connarus semidecandrus Jack (Family: connaraceae) is a medicinal plant known for its wide distribution throughout Southeast Asia. Renowned for its diverse therapeutic properties, it has been traditionally used for treating fever, skin irritation, and colic. AIM OF THE STUDY: Numerous individuals suffer from skin issues, including wrinkles, hyperpigmentation, and inflammation, due to environmental factors. Although many drugs are available to treat skin problems, chemical drugs have many shortcomings and side effects. Therefore, natural products are attractive potential medicines for alleviating skin troubles. We recently showed that Connarus semidecandrus Jack ethanol extract (Cs-EE) has anti-alopecia potential. This paper aims to explore the potential skin-protective effects and underlying molecular mechanisms of Connarus semidecandrus Jack in UVB-induced human keratinocytes (HaCaT). MATERIALS AND METHODS: Before utilization, Cs-EE was dissolved in dimethyl sulfoxide (DMSO) and was preserved at a temperature of -20 °C. The phytochemical constituents of Cs-EE were detected by gas chromatography-mass spectrometry analysis (GC-MS). Sequentially, HaCaT cells were exposed to varying concentrations of Cs-EE prior to ultraviolet B (UVB) irradiation. Evaluations of cellular responses in HaCaT cells, including assessments of cell viability, deoxyribonucleic acid (DNA) damage, and gene and protein expressions, were carried out. To explore the specific signaling pathway involved, we conducted a luciferase assay in addition to validating these pathways using Western blot analysis. RESULTS: Nitric oxide (NO) and intracellular reactive oxygen species were decreased. Melanin production through the activation of melanocytes by α-melanocyte-stimulating hormone (MSH) was also inhibited by Cs-EE. Furthermore, the mRNA expression levels of key factors such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), MMP-1, MMP-3, and MMP-9 exhibited a remarkable decrease. In addition, the phosphorylation of TAK1 within the signaling cascade exhibited a decline, and the activities of the transcription factor AP-1 were decreased according to a luciferase reporter assay. CONCLUSIONS: Taken together, these findings suggest that the anti-inflammatory, anti-aging, and anti-apoptotic effects of Cs-EE indicate the compound's potential usefulness as a natural component in pharmaceutical and cosmetic products.

Role of histone methylation in skin cancers: Histone methylation-modifying enzymes as a new class of targets for skin cancer treatment.

Histone methylation, one of the most prominent epigenetic modifications, plays a vital role in gene transcription, and aberrant histone methylation levels cause tumorigenesis. Histone methylation is a reversible enzyme-dependent reaction, and histone methyltransferases and demethylases are involved in this reaction. This review addresses the biological and clinical relevance of these histone methylation-modifying enzymes for skin cancer. In particular, the roles of histone lysine methyltransferases, histone arginine methyltransferase, lysine-specific demethylases, and JmjC demethylases in skin cancer are discussed in detail. In addition, we summarize the efficacy of several epigenetic inhibitors targeting histone methylation-modifying enzymes in cutaneous cancers, such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. In conclusion, we propose histone methylation-modifying enzymes as novel targets for next-generation pharmaceuticals in the treatment of skin cancers and further provide a rationale for the development of epigenetic drugs (epidrugs) that target specific histone methylases/demethylases in cutaneous tumors.