Background: Particulate matter (PM) is a major environmental pollutant that induces oxidative stress, inflammation, and extracellular matrix (ECM) degradation, leading to skin damage and accelerated aging. Xanthorrhizol (XAN), a bioactive compound derived from Curcuma xanthorrhiza Roxb., exhibits anti-inflammatory and antioxidative properties, making it a promising candidate for protecting against PM-induced skin damage. This study investigated the protective effects of XAN and C. xanthorrhiza supercritical extract (CXSE) on PM-exposed skin cells. Methods: A 3D-reconstructed skin model and HaCaT human keratinocytes were exposed to PM (100 µg/mL) with or without CXSE or XAN. Histological analysis, enzyme-linked immunosorbent assay (ELISA), Western blot, reverse transcription-polymerase chain reaction (RT-PCR), and reporter gene assays were performed to assess the ECM integrity, inflammatory cytokine production, aryl hydrocarbon receptor (AhR) activation, and oxidative stress responses. Results: PM exposure activates AhR and mitogen-activated protein kinases (MAPK) signaling, increases reactive oxygen species (ROS) levels, and upregulates matrix metalloproteinases (MMPs) and inflammatory cytokines. CXSE and XAN suppresses AhR-mediated transcriptional activity and downregulates the expression of AhR target genes. Additionally, CXSE and XAN reduces ROS production by upregulating antioxidant enzyme-related genes. Conclusions: CXSE and XAN protect against PM-induced skin damage by inhibiting oxidative stress, inflammation, and ECM degradation, highlighting their potential as natural anti-pollution skincare ingredients.

Background/Objectives: Macrophages polarized into M1 and M2 phenotypes differentially regulate immune and drug responses. Despite their distinct functional roles, differences in UDP-glucuronosyltransferase (UGT) expression and activity between M1 and M2 macrophages remain poorly understood. This study aimed to characterize differential UGT expression in M1 and M2 macrophages and to elucidate how UGT-mediated prostaglandin E₂ (PGE₂) glucuronidation modulates macrophage inflammatory responses. Methods: THP-1 cells were chemically differentiated into macrophages (M0) and subsequently polarized into M1 and M2 phenotypes. UGT expression profiles were assessed using RT-PCR, quantitative RT-PCR, and Western blotting. UGT enzymatic activity was compared by quantifying glucuronide metabolites derived from UGT-specific substrates using LC-MS/MS, along with measurement of free PGE₂ and PGE₂-glucuronide by ELISA. Pro-inflammatory cytokine expression and secretion in M1 macrophages were quantified using quantitative RT-PCR and ELISA. Results: UGT1A1, UGT1A4, UGT1A5, UGT1A9, and UGT2B7 were markedly upregulated in M1 compared with M2 macrophages at both the mRNA and protein levels. UGT enzymatic activity was significantly higher in M1 macrophages (p < 0.01) and was attenuated in a concentration-dependent manner by the UGT inhibitor diclofenac. Enhanced UGT activity in M1 macrophages was reflected by increased formation of estradiol-3-glucuronide and naloxone-3-glucuronide (both p < 0.01). Furthermore, PGE₂ glucuronidation was more pronounced in M1 macrophages, and inhibition of UGTs with atazanavir reduced PGE₂-glucuronide formation and pro-inflammatory cytokine production, including IL-1β, IL-6, and TNF-α. Conclusion: UGT-mediated PGE₂ glucuronidation in M1 macrophages plays a critical role in sustaining pro-inflammatory cytokine responses. These findings identify UGTs as important regulators of macrophage phenotype and inflammatory signaling.

Background/Objectives: Macrophages polarized into M1 and M2 phenotypes differentially regulate immune and drug responses. Despite their distinct functional roles, differences in UDP-glucuronosyltransferase (UGT) expression and enzymatic activity between M1 and M2 macrophages remain poorly understood. This study aimed to characterize differential UGT expression in M1 and M2 macrophages and to elucidate how UGT-mediated prostaglandin E₂ (PGE₂) glucuronidation modulates macrophage inflammatory responses. Methods: THP-1 cells were chemically differentiated into macrophages (M0) and subsequently polarized into M1 and M2 phenotypes. UGT expression profiles were assessed using RT-PCR, quantitative RT-PCR (qRT-PCR), and Western blot. UGT activity was compared by quantifying glucuronide metabolites derived from UGT-specific substrates using LC-MS/MS, along with measurement of free PGE₂ and PGE₂-glucuronide by ELISA. Pro-inflammatory cytokine expression and secretion in M1 macrophages were quantified using qRT-PCR and ELISA. Results: Expression of UGT1A1, UGT1A4, UGT1A5, UGT1A9, and UGT2B7 were markedly higher in M1 compared with M2 macrophages at both the mRNA and protein levels. Enhanced UGT activity in M1 macrophages was reflected by increased formation of estradiol-3-glucuronide and naloxone-3-glucuronide (both p < 0.01) and was attenuated in a concentration-dependent manner by diclofenac. Furthermore, PGE₂ glucuronidation was more pronounced in M1 macrophages, and inhibition of UGTs with atazanavir reduced PGE₂-glucuronide formation and pro-inflammatory cytokine production, including IL-1β, IL-6, and TNF-α. Conclusion: UGT-mediated PGE₂ glucuronidation in M1 macrophages contributes to the regulation of pro-inflammatory cytokine production. Collectively, these findings support a role for UGTs as modulators of inflammatory signaling, with differential expression and activity between M1 and M2 macrophages.