Psoriasis is an autoimmune and inflammatory skin disease. Psoriatic patients express higher levels of plasma homocysteine (Hcy) concentration and pro-inflammatory mediators than healthy people; this is frequently associated with vitamin D deficiency. The aim of this clinical study was to investigate the effects of high doses of vitamin D supplementation on the parameters of Hcy metabolism and cytokines in sera of psoriatic patients. This prospective study was conducted on 40 psoriatic patients who had the vitamin D deficiency. All patients received vitamin D 5000 IU/day for three months. Clinical and biochemical measurements were taken at baseline and at follow up (3 months). The results showed that the severity of clinical features, measured by the psoriasis area severity index (PASI) score, were considerably improved in patients after vitamin D supplementation. After vitamin D supplementation, most of the patients (n = 25 or 62.5%) had mild clinical form (p < 0.001). After twelve weeks of intervention period, there were significant increases in vitamin D and B₁₂ serum levels in comparison to the levels that had been measured at the beginning of the study (56.77 ± 14.66 nmol/L and 301.08 ± 95.02 pg/mL vs. 103.85 ± 32.20 nmol/L and 362.81 ± 118.56 pg/mL, respectively; p < 0.001). Moreover, serum levels of Hcy and folate were significantly lower at the end of the study in comparison with the initial levels (12.45 ± 1.92 µmol/L and 8.01 ± 3.88 mg/mL vs. 10.38 ± 1.66 µmol/L and 6.27 ± 2.60 mg/mL, respectively). High doses of vitamin D supplementation led to a significant decrease in pro-inflammatory cytokines (IFN-ɤ, TNF-α, IL-1β, IL-6, IL-8, and IL-17) and high-sensitivity C-reactive protein (hsCRP), whereas the production of anti-inflammatory cytokines (IL-10, IL-5) was up-regulated. In conclusion, supplementation with high doses of vitamin D could be one of the possible preventive and therapeutic measures to reduce systemic inflammation in psoriatic patients.

Oxidative stress is a critical pathophysiological factor in sepsis. Ursodeoxycholic acid (UDCA), a bile acid with anti-inflammatory, antioxidant, and anti-apoptotic properties, may protect against lipopolysaccharide (LPS)-induced myocardial injury. In an experimental study, 32 male Wistar rats were randomly assigned to four groups: control, LPS, UDCA, and UDCA + LPS. UDCA was administered orally for 10 days prior to LPS-induced endotoxemia. Serum levels of high-sensitive troponin I (hsTnI), homocysteine, and oxidative stress markers were measured, and immunohistochemistry and immunofluorescence were used to assess inflammation (nuclear factor kappa B, NF-κB), apoptosis (caspase 3), and signaling pathways related to protein kinase B (Akt)/NF-κB and silent information regulator 1 (SIRT1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1). UDCA pretreatment significantly reduced myocardial pathological changes, serum hsTnI, homocysteine, and total oxidative stress compared with LPS alone. It enhanced catalase (CAT) activity and glutathione (GSH) levels while lowering thiobarbituric acid reactive substances (TBARS) and nitrite concentrations in cardiac tissue. UDCA modulated cellular signaling by decreasing Akt phosphorylation and activating the SIRT1/Nrf2/HO-1 pathway. These results indicate that UDCA protects the heart from LPS-induced damage by reducing oxidative stress, inflammation, and apoptosis. UDCA modulates cellular signaling by decreasing pro-inflammatory pathways and activating anti-inflammatory pathways associated with SIRT1/Nrf2/HO-1 signaling, emphasizing its key role in myocardial protection during sepsis.

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, despite significant advances in diagnostics and pharmacotherapy. This persistent burden has shifted attention toward adjunct therapeutic strategies targeting key mechanisms of myocardial and vascular injury, including oxidative stress, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, apoptosis, inflammation, endothelial dysfunction, and metabolic dysregulation. A particular interest of contemporary research is focused on bile acid (BA) signaling through nuclear and membrane receptors, primarily the Farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5), as central regulators of metabolic, inflammatory, and vascular responses. Ursodeoxycholic acid (UDCA), a hydrophilic BA widely used to treat hepatobiliary disorders, has emerged as a potential modulator of cardiometabolic processes. UDCA exerts direct effects through low-affinity but functionally relevant activation of the TGR5 receptor, as well as indirect effects through alterations in BA pool composition, thereby influencing FXR/TGR5 signaling pathways. Experimental studies suggest that UDCA reduces oxidative stress, stabilizes mitochondrial function, alleviates ER stress, suppresses apoptosis and inflammation, and improves endothelial function and nitric oxide (NO) bioavailability. Despite promising mechanistic evidence, currently available clinical data remain limited and are largely based on small studies and surrogate biomarkers, without confirmation of benefits in terms of major cardiovascular outcomes. This review summarizes current knowledge regarding the role of UDCA in the modulation of BA receptor signaling and its potential relevance for cardiovascular protection.