Melanoma is a skin cancer originating from melanocytes. The global incidence rate of melanoma is rapidly increasing, posing significant public health challenges. Identifying effective therapeutic agents is crucial in addressing this growing problem. Natural products have demonstrated promising anti-tumor activity. In this study, a plant flavonoid, taxifolin, was screened using Weighted Correlation Network Analysis (WGCNA) in combination with the Connectivity Map (CMAP) platform. Taxifolin was confirmed to inhibit the proliferation, migration, and invasion ability of melanoma A375 and MV-3 cells by promoting apoptosis. Additionally, it suppressed the Epithelial-Mesenchymal Transition (EMT) process of melanoma cells. Cyber pharmacological analysis revealed that taxifolin exerts its inhibitory effect on melanoma through the PI3K/AKT signaling pathway, specifically by downregulating the protein expression of p-PI3K and p-AKT. Notably, the addition of SC-79, an activator of the PI3K/AKT signaling pathway, reversed the effects of taxifolin on cell migration and apoptosis. Furthermore, in vivo experiments demonstrated that taxifolin treatment slowed tumor growth in mice without significant toxic effects. Based on these findings, taxifolin holds promise as a potential drug for melanoma treatment.

The accumulation of reactive oxygen species (ROS) in the skin following UVB exposure is a key contributor to ultraviolet-induced skin photodamage. Orientin, a bioactive flavonoid, has demonstrated antioxidant properties in previous studies. However, its efficacy in treating skin photodamage remains inadequately understood. This study investigates the effects of orientin in preventing UVB-induced immortalized human keratinocytes (HaCaT cells) and BALB/c mouse skin photodamage by activating the AMPK/Nrf2 axis. Results show that orientin protects HaCaT cell viability after UVB exposure, reduces ROS levels, and upregulates antioxidant enzymes, including SOD1, HO-1, and NQO-1, while concurrently suppressing the expression of inflammatory mediators such as COX-2, IL-6, and IL-8. Additionally, orientin promotes AMPK phosphorylation, which facilitates Nrf2 nuclear translocation, thereby enhancing the antioxidant defense of cells. This effect is diminished upon inhibition of AMPK or Nrf2. In the BALB/c mouse model of photodamage, topical application of orientin alleviates symptoms like skin roughness, scaling, and erythema induced by UVB irradiation, while also elevating antioxidant enzyme expression in skin tissues. These findings suggest that orientin mitigates ultraviolet-induced skin photodamage both in vitro and in vivo, boosts cellular antioxidant capacity, and diminishes inflammatory responses, suggesting its potential for further exploration in skin photodamage management.

Background: Psoriasis remains incurable, driving the need for new treatments. This study evaluated the therapeutic effects of oleanolic acid on IMQ-induced psoriasis model mice and used network pharmacology and molecular docking to predict its mechanism of action.Methods: This study assessed the different concentrations (1%, 5%, 10%) of oleanolic acid cream effects on IMQ-induced psoriasis in female BALB/c mice, evaluating therapeutic outcomes via PASI scores, skin lesion staining, and inflammatory factor detection. Network pharmacology and molecular docking predicted OA’s mechanism. Key targets were identified using databases and software analyses.Results: Oleanolic acid can treat skin damage in psoriasis model mice and improve systemic inflammatory responses. Network pharmacology results identified important potential targets for OA treatment of psoriasis, including HSP90AA1, STAT3, MAPK3, HSP90AB1, PPARG, PTGS2, AR, CDK1. GO functional enrichment analysis involved biological functions such as inflammation response, signal transduction, G protein-coupled receptor signaling pathway, etc. KEGG pathway enrichment analysis involved signaling pathways such as neuroactive ligand-receptor interaction, PPAR signaling pathway, Th17 cell differentiation, etc. Molecular docking results showed good affinity between oleanolic acid and MAPK3, STAT3, AR, PPARG.Conclusion: Oleanolic acid has therapeutic effects on psoriasis, with possible target points being MAPK3, STAT3, AR, and PPARG, involving processes such as inflammation response, negative regulation of cell proliferation, and Th17 cell differentiation.

Introduction: Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality worldwide. Although targeted therapies and immunotherapies have improved treatment outcomes, the development of drug resistance continues to limit clinical efficacy. This study aims to explore the potential therapeutic effects and molecular mechanisms of pine needle oil and its key bioactive component, bornyl acetate (BA), in NSCLC. Methods: The anti-cancer activity of BA was evaluated in vitro using two NSCLC cell lines, A549 and NCI-H460. Cell proliferation, invasion, migration, colony formation, and apoptosis were assessed. Mechanistic studies focused on the PI3K/AKT signaling pathway and ABCB1 expression levels. The AKT agonist SC79 was used to rescue phenotypic effects. In vivo, subcutaneous xenograft models generated with NCI-H460 and A549 cells were employed to examine the antitumor efficacy of BA. Results: BA significantly inhibited proliferation, invasion, migration, and colony formation in A549 and NCI-H460 cells and promoted apoptosis. Mechanistically, BA suppressed the PI3K/AKT pathway, leading to downregulation of ABCB1. The AKT activator SC79 partially reversed BA-induced inhibition of invasion and migration. In vivo, BA treatment markedly attenuated the growth of both A549 and NCI-H460 xenograft tumors. Discussion: These results demonstrate that BA exerts potent anti-tumor effects in NSCLC by inhibiting the PI3K/AKT/ABCB1 axis. The findings provide a mechanistic rationale for the development of BA and other natural product-based therapies, particularly for the treatment of drug-resistant NSCLC.

Introduction: Nuclear receptor subfamily five group A member two (NR5A2) plays a key role in the development of many tumor types, while it is uncertain in cutaneous squamous cell carcinoma (cSCC). The aim of this work was to determine the role of NR5A2 in cSCC proliferation, and to determine whether NR5A2 mediates the effect of cisplatin in cSCC.Methods: We performed a systematic study of existing data and conducted a preliminary bioinformatics analysis of NR5A2 expression in cSCC using bioinformatics databases. Immunohistochemical staining was performed on cSCC tissues of seven patients to study NR5A2 expression. NR5A2 expression was examined in human keratin‐forming cells (HaCaT) and human cSCC cells (A431, Colo‐16, SCL‐1, SCL‐2, and HSC‐5). Stable A431 and SCL‐2 cell lines consisting of sh‐RNA‐NR5A2 were constructed to detect changes in cell proliferation, cell cycle, apoptosis, and to determine the key proteins in the Wnt/β‐catenin pathway. We also investigated changes in the effects of cisplatin on cSCC cells by CCK‐8, clone formation assay, and Flow apoptosis assay after NR5A2 knockdown.Results: NR5A2 showed enhanced expression in cSCC tissues than in healthy tissues. Downregulation of NR5A2 in cSCC cells led to the formation of a less malignant phenotype. In contrast, the proliferative capacity of the cSCC cells was enhanced posttreatment with RJW100, an NR5A2 agonist. Additionally, NR5A2 knockdown led to a decrease in the expression level of the proteins in the Wnt/β‐catenin pathway, and this inhibition was reversed by LiCl and recombinant antibody, Wnt3a. Moreover, NR5A2 knockdown resulted in diminished proliferative capacity and increased apoptotic cells after the addition of cisplatin.Conclusion: NR5A2 plays a crucial role in the progression of cSCC, and the Wnt/β‐catenin signaling pathway may be involved in the regulation of NR5A2‐mediated cSCC. Knockdown of NR5A2 enhanced both the proliferation inhibiting and apoptosis promoting effects of cisplatin on cSCC.