Exposure to particulate matter 2.5 (PM2.5) can negatively impact human skin, leading to issues such as wrinkle formation, skin aging, atopic dermatitis, and pigment spots. Galangin, a flavonoid known for its antioxidant property, was investigated for its protective effects on human HaCaT keratinocytes against PM2.5-induced endoplasmic reticulum (ER) stress and cellular senescence via the activation of the p38 mitogen-activated protein kinase (MAPK)-mediated signaling pathway. In this study, cells were pretreated with galangin before exposure to PM2.5. Galangin mitigated the PM2.5-induced increases in reactive oxygen species (ROS), intracellular calcium, and ER stress-associated proteins. Additionally, galangin counteracted PM2.5-induced cell cycle arrest in the G0/G1 phase and restored the levels of cell cycle regulators, matrix metalloproteinases, and inflammatory cytokines. Moreover, the p38 MAPK inhibitor, along with galangin, reversed cell cycle arrest, reduced cell proliferation, and alleviated cellular senescence triggered by PM2.5. Overall, galangin protected cells against PM2.5-induced ER stress and senescence via the ROS-p38 MAPK pathway.

Antae-eum (ATE), a traditional herbal formula consisting of ten medicinal herbs, has been primarily used for fetal health and the alleviation of abdominal pain during pregnancy. However, comprehensive experimental studies on its pharmacological effects and mechanisms of action are lacking. Local inflammatory responses in the uterus play a crucial role in embryo implantation and early placental development, while excessive inflammation can lead to implantation failure, recurrent miscarriage, and preeclampsia. In the present study, we hypothesized that ATE may help promote pregnancy stability by modulating the inflammatory responses during pregnancy, and investigated the effect of ATE on the inflammatory response. First, the marker compounds in ATE were identified using a high-performance liquid chromatography system. Then, we assessed inflammatory cytokine production, expression changes related to inflammatory signaling, as well as the expression and flux of autophagic markers in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). In ATE, the nineteen marker compounds including baicalin, hesperidin, paeoniflorin, and wogonoside were detected, and the most abundant was baicalin. The anti-inflammatory effect of ATE is achieved by reducing pro-inflammatory cytokine production and further downregulating the TLR4-mediated MAPK and NF-κB signalings. ATE suppressed autophagic flux by disrupting the accumulation of FOXO3a. In summary, our results indicate that ATE exerts anti-inflammatory effects by the blockade of autophagic flux. These findings suggest that ATE has potential as a therapeutic agent for various inflammatory diseases, including inflammatory-related reproductive disorders.

Fucoxanthin is a naturally derived carotenoid in marine brown algae that has potential curative benefits for treating diseases such as cancer, diabetes, and obesity. Exposure to particulate matter with a diameter of ≤2.5 µm (PM2.5) is associated with the occurrence of cardiac disorders, cancer, and senescence. The primary objective of this study was to determine the protective effects of fucoxanthin against PM2.5-induced dysfunction of human HaCaT keratinocytes. Fucoxanthin decreased PM2.5-induced production of reactive oxygen species and mitigated lipid peroxidation, DNA damage, and depolarization of the mitochondrial membrane potential. Fucoxanthin inhibited PM2.5-mediated activation of nuclear factor κB and Nod-like receptor family protein 3 inflammasome and the release of proinflammatory cytokines such as interleukin (IL)-1, IL-6, and cyclooxygenase-2. Additionally, fucoxanthin decreased dysfunctional cell proliferation and reversed the cell cycle arrest in the G0/G1 phase. Docking and network analyses revealed that fucoxanthin interacted with seven major proteins related to inflammation and senescence. Senescence-associated β-galactosidase and matrix metalloproteinases were downregulated by fucoxanthin following exposure to PM2.5. Conclusively, fucoxanthin attenuates the cellular oxidative stress caused by PM2.5 and suppresses inflammatory responses and senescence, thereby implying its potential in alleviating PM2.5-induced skin damage.

ABSTRACTBenign prostate hyperplasia (BPH) is characterized by abnormal prostate epithelial and stromal cell growth, which leads to bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTS). BPH pathogenesis involves key signaling pathways, including androgen/androgen receptor (AR) and transforming growth factor‐beta (TGF‐β)/Smad, which contribute to cell proliferation, transformation, and epithelial–mesenchymal transition (EMT). To date, the effect of Hovenia dulcis honey (HH) on BPH has not been reported. Herein, in vivo and in vitro BPH models were used to determine whether HH has therapeutic effects and its underlying mechanisms, if present. To evaluate the anti‐BPH effect of HH in vivo, mice were treated with testosterone propionate (TP; 10 mg/kg, s.c.), finasteride (Fi; 10 mg/kg, i.p.), or HH (600 mg/kg, p.o.) for 4 weeks. Additionally, HH in vitro efficacy was evaluated using a dihydrotestosterone (DHT)‐stimulated RWPE‐1 prostate cell model. HH significantly reduced prostate size, epithelial thickness, and markers of AR signaling (prostate‐specific antigen [PSA], proliferating cell nuclear antigen [PCNA], and DHT) as well as exhibited anti‐inflammatory effects by lowering the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase‐2 (COX‐2), interleukin‐6 (IL‐6), and tumor necrosis factor‐α (TNF‐α) and inhibited the EMT process by decreasing α‐smooth muscle actin (α‐SMA), neural cadherin (N‐cadherin), and vimentin levels while restoring epithelial cadherin (E‐cadherin) expression. These findings suggest that HH inhibits the androgen/AR and TGF‐β/Smad signaling pathways and may offer a novel therapeutic approach for BPH treatment.

Atopic dermatitis (AD), a chronic inflammatory skin condition, is a common allergic disorder. The human skin, the largest organ, serves as the first barrier in protecting the body against various external threats. Human epidermal keratinocytes (HEKs) in the epidermal layer and human dermal fibroblasts (HDFs) in the dermis of the skin are implicated in AD-associated skin inflammation through the secretion of diverse inflammatory mediators, including chemokines. Sigesbeckia pubescens Makino (SP), a traditional Korean and Chinese herbal remedy, is used for treating inflammatory conditions. While several pharmacological effects of SP extract (SPE) have been documented, its specific inhibitory effect on AD-related skin inflammation remains unexplored. Hence, oral administration of SPE to NC/Nga mice reduced the severity of house dust mite extract-induced dermatitis, accompanied by lowered levels of serum inflammatory mediators, decreased epidermal thickness, reduced mast cell infiltration, and restoration of skin barrier function within skin lesions. In conclusion, SPE has demonstrated the ability to alleviate skin inflammation and protect the skin barrier and shows potential as a therapeutic option for AD. SPE inhibited proinflammatory chemokine production by modulating the Janus kinase (JAK) 2/signal transducer and activator of transcription proteins (STAT) 1/STAT3 signaling pathway in IFN-γ- and TNF-α-stimulated skin cells.

Ficus erecta Thunb. has been used to treat various inflammatory diseases owing to its anti-inflammatory and antioxidative properties. However, scientific evidence on the safety of F. erecta extract is limited. We evaluated the genotoxicity of ethanol extract of F. erecta (EEFE) using multiple tests. The bacterial reverse mutation (Ames) test showed that EEFE treatment of five bacterial strains (Salmonella typhimurium TA98, TA100, TA1535, TA1537, and Escherichia coli WP2uvrA) did not affect the number of revertant colonies in the absence or presence of S9 mix, a metabolic activator, up to a concentration of 312.5 µg/plate. The number of chromosomal aberrations associated with EEFE was similar to that in the negative controls, with no significant increase up to a concentration of 31.3 µg/mL EEFE. The chromosomal aberration assay showed that EEFE was not associated with any abnormalities in combination with or without S9 mix. The in vivo micronucleus test revealed that EEFE did not influence the frequency of bone marrow micronuclei up to 2000 mg/kg body weight of male ICR mice. Moreover, no changes in mouse body weight or mortality rates were observed. Our study demonstrates the safety of EEFE in genotoxicity tests, providing proof-of-concept for its use as a medicine and functional food.

This study aimed to evaluate the effect of fermented garlic extract (FGE) containing nitric oxide (NO) on arterial pulse waves in hypertension patients using a noninvasive radial artery tonometry device. Forty-one participants were recruited for this study investigating changes in arterial pulse wave characteristics following the ingestion of FGE containing NO over a 2-week period. Arterial pulse wave measurements were taken before and 15, 20, and 25 min after FGE administration and 2 weeks after the end of the ingestion period. One participant withdrew, and five participants refused to undergo pulse wave measurements. These six participants were excluded, resulting in 35 participants being included for analysis. Fifteen minutes after the administration of FGE with NO, the systolic and diastolic blood pressure (BP) significantly decreased. The radial augmentation index (RAI), width (w), width/time (w/t) ratio, and stroke volume index (SVI) significantly decreased, while the mean pulse width significantly increased. Notably, the RAI, w, w/t ratio, and SVI exhibited a decreasing trend at 15, 20, and 25 min compared to the values before the administration of FGE. After 2 weeks of ingestion, no pulse wave variables showed significant changes compared to those before the administration of FGE. The oral administration of low-dose FGE containing NO showed acute positive effects on the wrist artery, including a reduction in BP and an improvement in arterial stiffness. These findings suggest that this study successfully evaluated the effects of FGE containing NO using quantitative and objective pulse parameters as noninvasive indicators.