Endothelial dysfunction is closely linked to inflammation and oxidative stress and ultimately contributes to the development of cardiovascular diseases. Lipopolysaccharide (LPS), a major component of Gram-negative bacteria, induces vascular inflammation and oxidative damage in experimental models. Curcumin (Cur), a polyphenol from Curcuma longa, is well known for its anti-inflammatory and antioxidant properties. In this study, we examined the protective effects of CUD003, a novel synthetic Cur derivative, on the LPS-induced impairment of endothelium-dependent relaxation in the thoracic aorta of mice. Male ICR mice were pretreated with CUD003 or Cur (3 or 10 mg/kg, p.o.) 30 min prior to LPS injection (10 mg/kg, i.p.). Twenty-four hours after LPS injection, vascular reactivity was assessed in isolated aortic rings by evaluating vasorelaxation and vasoconstriction responses. LPS markedly impaired acetylcholine-induced vasorelaxation in the phenylephrine (PE)-precontracted aortic rings, while PE-induced contraction and sodium nitroprusside-induced relaxation were preserved, indicating that LPS impaired endothelium-dependent relaxation without affecting smooth muscle function. Immunohistochemical analysis revealed a reduction in eNOS expression and elevated levels of TNF-α, COX-2, O₂⁻, and malondialdehyde, indicating enhanced inflammation and oxidative stress in the aorta. Pretreatment with CUD003 (10 mg/kg) significantly ameliorated these changes and showed superior protective effects compared to the same dose of Cur. These findings suggest that CUD003 protects against LPS-induced vascular dysfunction and suppresses inflammation and oxidative stress, supporting its potential as a preventive candidate against vascular inflammation and dysfunction.

Psoriasis is a chronic inflammatory skin disease characterized by erythema, infiltration, and scaling, which is mainly caused by interleukin (IL)-17. The use of molecular targeted drugs in specific therapies offers high efficacy; however, high medical costs and a significant risk of side effects highlight the need for novel therapeutic agents. We previously observed that Morus alba extract (MAE) suppressed IL-17-induced CCL20 mRNA expression in normal human epidermal keratinocytes (NHEKs). In this study, we focused on the IL-17 signaling pathway and investigated the effects of pentacyclic triterpenoids, betulinic acid (BA), and ursolic acid (UA), which are present in MAE, on NHEK cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) revealed that both BA and UA suppressed CCL20 expression, while only UA alone inhibited CCL20 release. ELISA using specific inhibitors demonstrated that both the p38 and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways were crucial for IL-17-induced CCL20 release in NHEK. UA effectively suppressed ERK1/2 nuclear localization and moderately affected p38 phosphorylation. These results indicated that UA is a potential seed compound for psoriasis treatment through its targeting of the IL-17 pathway.

Numerous natural extracts and compounds have been evaluated for their ability to mitigate the adverse effects of ultraviolet (UV) overexposure. However, variability in the UV doses that trigger biological responses across studies likely arises from inconsistencies in UV exposure standardization. We hypothesize that these discrepancies are due to variations in culture plates and dishes. The UV dose (D) required to reduce cell viability by 50% differed by a factor of ten between 3.5 cm dishes and 96-well plates. Similarly, the EC₅₀ dose for IL-6 release (D_1/2) varied, potentially correlating with the surface area (S). UV exposure to wells with increasing height in 3.5 cm dishes resulted in a decrease in IL-6 release, suggesting that the greater the well height, the more it may influence UV exposure through reflection or shielding effects, thereby contributing to the physiological effects on the cells. To compare these differences among plates, we defined the height-to-diameter ratio (r). Analysis revealed a linear correlation between D_1/2 and S in a log-log plot, and between D_1/2 and r in a semi-log plot. From this, we defined two empirical indices σ and ρ for UV dose adjustment. A deductive model was also developed to derive a D′ value that adjusts UV doses without requiring training. As with σ and ρ, the UV dose D was effectively adjusted using D′ as well. These attempts suggest that D′ offers a foundational framework for evaluating UVB effects on cultured cells.