Anti-tumor activity of Tremella fuciformis polysaccharides (TFPS) has been widely reported, but its mechanism remains poorly understood. In this study, we established an in vitro co-culture system (B16 melanoma cells and RAW 264.7 macrophage-like cells) to explore the potential anti-tumor mechanism of TFPS. Based on our results, TFPS exhibited no inhibition on the cell viability of B16 cells. However, significant apoptosis was observed when B16 cells were co-cultured with TFPS-treated RAW 264.7 cells. We further found that mRNA levels of M1 macrophage markers including iNOS and CD80 were significantly upregulated in TFPS-treated RAW 264.7 cells, while M2 macrophage markers such as Arg-1 and CD 206 remained unchanged. Besides, the migration, phagocytosis, production of inflammatory mediators (NO, IL-6 and TNF-α), and protein expression of iNOS and COX-2 were markedly enhanced in TFPS-treated RAW 264.7 cells. Network pharmacology analysis indicated that MAPK and NF-κB signaling pathways may be involved in M1 polarization of macrophages, and this hypothesis was verified by Western blot. In conclusion, our research demonstrated that TFPS induced apoptosis of melanoma cells by promoting M1 polarization of macrophages, and suggested TFPS may be applied as an immunomodulatory for cancer therapy.
23 November 2023 in Nanomedicine: Nanotechnology, Biology and Medicine
Zingiber striolatum Diels (Z. striolatum), a widely popular vegetable in China, is famous for its medicinal and nutritional values. However, the anti-inflammatory effects of essential oil from Z. striolatum (EOZS) remain unclear. In this study, EOZS from seven regions in China were extracted and analyzed by GC–MS. LPS-induced RAW264.7 cells and 12-O-Tetradecanoylphorbol 13-acetate (TPA)-stimulated mice were used to evaluate the anti-inflammatory effects of EOZS. Results show that 116 compounds were identified in EOZS from seven locations. Samples 2, 4 and 5 showed the best capability on DPPH radical scavenging and NO inhibition. They also significantly reduced the production of ROS, pro-inflammatory cytokines, macrophage morphological changes, migration and phagocytic capability. Transcriptomics revealed MAPK and NF-κB signaling pathways may be involved in the anti-inflammatory mechanism, and the predictions were proven by Western blotting. In TPA-induced mice, EOZS reduced the degree of ear swelling and local immune cell infiltration by blocking the activation of MAPK and NF-κB signaling pathways, which was consistent with the in vitro experimental results. Our research unveils the antioxidant capability and potential molecular mechanism of EOZS in regulating inflammatory response, and suggests the application of EOZS as a natural antioxidant and anti-inflammatory agent in the pharmaceutical and functional food industries.
Glycyrrhetinic acid (GA) is a saponin compound, isolated from licorice (Glycyrrhiza glabra), which has been wildly explored for its intriguing pharmacological and medicinal effects. GA is a triterpenoid glycoside displaying an array of pharmacological and biological activities, including anti-inflammatory, anti-bacterial, antiviral and antioxidative properties. In this study, we investigated the underlying mechanisms of GA on acne vulgaris through network pharmacology and proteomics. After the intersection of the 154 drug targets and 581 disease targets, 37 therapeutic targets for GA against acne were obtained. A protein–protein interaction (PPI) network analysis highlighted TNF, IL1B, IL6, ESR1, PPARG, NFKB1, STAT3 and TLR4 as key targets of GA against acne, which is further verified by molecular docking. The experimental results showed that GA inhibited lipid synthesis in vitro and in vivo, improved the histopathological damage of skin, prevented mast cell infiltration and decreased the level of pro-inflammatory cytokines, including TNF-α, IL-1β and IL-6. This study indicates that GA may regulate multiple pathways to improve acne symptoms, and the beneficial effects of GA against acne vulgaris might be through the regulation of sebogenesis and inflammatory responses.
2-Ethylhexyl-4-methoxycinnamate (EHMC) is among the most widely adopted organic UVB filters in commercial sunscreens. Nevertheless, its practical application potential is limited by unfavorable formulation compatibility and safety risks stemming from systemic exposure after topical administration. In this study, an oil-continuous structured gel matrix consisting of EHMC, disteardimonium hectorite (DDH) and dextrin palmitate (DP) was constructed to enhance UVB photoprotection and modulate the plasma exposure profile of EHMC following topical application. Comprehensive characterizations including rheology, XRD, Raman spectroscopy, FTIR spectroscopy, TGA and SEM collectively revealed that the combined incorporation of DDH and DP facilitates matrix structural rearrangement, enables EHMC to bind within the structured network, and promotes the formation of more intact continuous surface films. In vitro SPF assays demonstrated that the finished topical formulation SC-4 delivered superior UVB blocking efficacy compared with the EHMC-only control SC-1; furthermore, SC-4 exhibited improved short-term physical stability under the preset thermal and centrifugal acceleration test conditions. Follow-up skin safety assessments, mass spectrometry imaging (MSI) and pharmacokinetic assays verified that SC-4 elicited no remarkable acute skin irritation across all experimental conditions. Relative to SC-1, the reference formulation with EHMC as the sole UV filter, SC-4 displayed weaker EHMC-related distribution signals in skin tissues, accompanied by lower early plasma EHMC concentrations and a slightly lower AUC0–48h trend. Collectively, these findings indicate that DDH/DP co-assembly serves as a viable matrix-structuring strategy to modulate EHMC-related skin distribution and early plasma exposure. Further research into UVA blocking performance, photostability, skin retention and transdermal permeation profiles, as well as long-term storage stability, is required to advance the development of broad-spectrum sunscreen formulations built on this novel matrix platform.