Natural Product-Derived Compounds Targeting Keratinocytes and Molecular Pathways in Psoriasis Therapeutics.

Psoriasis is a chronic autoimmune inflammatory skin disorder that affects approximately 2-3% of the global population due to significant genetic predisposition. It is characterized by an uncontrolled growth and differentiation of keratinocytes, leading to the formation of scaly erythematous plaques. Psoriasis extends beyond dermatological manifestations to impact joints and nails and is often associated with systemic disorders. Although traditional treatments provide relief, their use is limited by potential side effects and the chronic nature of the disease. This review aims to discuss the therapeutic potential of keratinocyte-targeting natural products in psoriasis and highlight their efficacy and safety in comparison with conventional treatments. This review comprehensively examines psoriasis pathogenesis within keratinocytes and the various related signaling pathways (such as JAK-STAT and NF-κB) and cytokines. It presents molecular targets such as high-mobility group box-1 (HMGB1), dual-specificity phosphatase-1 (DUSP1), and the aryl hydrocarbon receptor (AhR) for treating psoriasis. It evaluates the ability of natural compounds such as luteolin, piperine, and glycyrrhizin to modulate psoriasis-related pathways. Finally, it offers insights into alternative and sustainable treatment options with fewer side effects.

Implications of Pony Lake Fulvic Acid for the Aggregation and Dissolution of Oppositely Charged Surface-Coated Silver Nanoparticles and Their Ecotoxicological Effects on Daphnia magna.

Citrate (Cit) and polyethylenimine (BPEI)-coated silver nanoparticles (AgNPs) were used to understand how the type of capping agents and surface charge affect their colloidal stability, dissolution, and ecotoxicity in the absence/presence of Pony Lake Fulvic Acid (PLFA). In the presence of PLFA, Cit-AgNPs were stabilized, while BPEI-AgNPs were aggregated. The aggregation of BPEI-AgNPs decreased with the time, and their stabilizing effect increased at high PLFA concentration. The dissolution also differed between both AgNPs and was influenced by the PLFA concentration. Generally, BPEI-AgNPs showed a lower amount of dissolved Ag than Cit-AgNPs. The dissolved Ag concentration decreased for both AgNPs at low PLFA concentration (5 mg/L). In contrast, the extent of nanoparticle dissolution increased at high PLFA concentration (30 mg/L) but only for BPEI-AgNPs. In the absence of PLFA, the ecotoxicity of Cit-AgNPs to Daphnia magna was higher than that of BPEI-AgNPs. However, the ecotoxicity of AgNPs in the presence of PLFA was up to 70% lower than in their absence. We demonstrated that the differences in colloidal stability, dissolution, and ecotoxicity may be attributed to the different capping agents, surface charge, and concentration of natural organic matter (NOM) as well as to the formation of dissolved Ag complexes with NOM.

Application of Multi-Species Microbial Bioassay to Assess the Effects of Engineered Nanoparticles in the Aquatic Environment: Potential of a Luminous Microbial Array for Toxicity Risk Assessment (LumiMARA) on Testing for Surface-Coated Silver Nanoparticles.

Four different manufactured surface-coated silver nanoparticles (AgNPs) with coating of citrate, tannic acid, polyethylene glycol, and branched polyethylenimine were used in this study. The toxicity of surface-coated AgNPs was evaluated by a luminous microbial array for toxicity risk assessment (LumiMARA) using multi-species of luminescent bacteria. The salt stability of four different AgNPs was measured by UV absorbance at 400 nm wavelength, and different surface-charged AgNPs in combination with bacteria were observed using scanning electron microscopy (SEM). Both branched polyethylenimine (BPEI)-AgNPs and polyethylene glycol (PEG)-AgNPs were shown to be stable with 2% NaCl (non-aggregation), whereas both citrate (Cit)-AgNPs and tannic acid (Tan)-AgNPs rapidly aggregated in 2% NaCl solution. The values of the 50% effective concentration (EC50) for BPEI-AgNPs in marine bacteria strains (1.57 to 5.19 mg/L) were lower than those for the other surface-coated AgNPs (i.e., Cit-AgNPs, Tan-AgNPs, and PEG-AgNPs). It appears that the toxicity of AgNPs could be activated by the interaction of positively charged AgNPs with the negatively charged bacterial cell wall from the results of LumiMARA. LumiMARA for toxicity screening has advantageous compared to a single-species bioassay and is applicable for environmental samples as displaying ranges of assessment results.

Effects of er-miao-san extracts on TNF-alpha-induced MMP-1 expression in human dermal fibroblasts.

BACKGROUND: Various health benefits have been attributed to Er-Miao-San (EMS), a traditional Chinese herbal formulation that contains equal amounts of cortex phellodendri (Phellodendron amurense Ruprecht) and rhizoma atractylodis (Atractylodes lancea D.C). However, its effect on the anti-inflammatory activity in human dermal fibroblasts (HDFs) and the mechanism underlying this effect are unknown. RESULTS: This study investigated the effects of EMS on TNF-α-induced MMP-1 expression in HDFs. Our data show that EMS inhibited TNF-α-induced MMP-1 expression in a concentration-dependent manner. Interestingly, EMS maintained IκB content without inhibiting the phosphorylation of MAPKs, which are well-established upstream kinases of NF-κB. Moreover, EMS reduced the level of nuclear p65 protein in HDFs. Luciferase assay revealed that EMS inhibits the transcriptional activity of NF-κB by stabilizing IκB. Our results show that EMS exerts its anti-inflammatory effect by inhibiting NF-κB-regulated genes such as IL-1ß and IL-8. Moreover, EMS effectively inhibited TNF-α-induced expression of MMP-1 via the NF-κB pathway. CONCLUSIONS: Taken together, our data suggest that EMS could potentially be used as an anti-inflammatory and anti-aging treatment.

Effects of Er-Miao-San extracts on TNF-alpha-indueed MMP-1 expression in human dermal fibroblasts

BACKGROUND: Various health benefits have been attributed to Er-Miao-San (EMS), a traditional Chinese herbal formulation that contains equal amounts of cortex phellodendri (Phellodendron amurense Ruprecht) and rhizoma atractylodis (Atractylodes lancea D.C). However, its effect on the anti-inflammatory activity in human dermal fibroblasts (HDFs) and the mechanism underlying this effect are unknown. RESULTS: This study investigated the effects of EMS on TNF-α-induced MMP-1 expression in HDFs. Our data show that EMS inhibited TNF-α-induced MMP-1 expression in a concentration-dependent manner. Interestingly, EMS maintained IkB content without inhibiting the phosphorylation of MAPKs, which are well-established upstream kinases of NF-kB. Moreover, EMS reduced the level of nuclear p65 protein in HDFs. Luciferase assay revealed that EMS inhibits the transcriptional activity of NF-kBbystabilizing IkB. Our results show that EMS exerts its anti-inflammatory effect by inhibiting NF-kB-regulated genes such as IL-1ß and IL-8. Moreover, EMS effectively inhibited TNF-α-induced expression of MMP-1 via the NF-kBpathway. CONCLUSIONS: Taken together, our data suggest that EMS could potentially be used as an anti-inflammatory and anti-aging treatment.

Redox bifunctionality in a Pt(ii) dithiolene complex of a tetrathiafulvalene diphosphine ligand.

The Pt(ii) dithiolene complex of a tetrathiafulvalene diphosphine ligand exhibits two reversible redox systems at close potentials, localized on the weakly interacting TTF (tetrathiafulvalene) and Pt(dmit) moieties.