This study aimed to confirm the immunomodulatory effects of fermented Benincasa hispida extract (HR1901-BS) on RAW 264.7 macrophages. B. hispida was fermented for 72 h using Bacillus subtilis CJH 101. To evaluate the efficacy of HR1901-BS in enhancing macrophage function, we measured and compared the levels of macrophage activation-related markers in HR1901-BS-stimulated RAW 264.7 cells. We evaluated the effects on nitric oxide (NO) production and the release of pro-inflammatory cytokines (interleukin IL-1β, IL-6, and tumor necrosis factor TNF-β) in the RAW 264.7 cell line. We confirmed that HR1901-BS affected macrophage activation by inducing a significantly high dose-dependent NO production and increasing the release of pro-inflammatory cytokines in RAW 264.7 macrophages. It also suggested that the immunomodulatory effect by HR1901-BS occurred mainly as a result of the activation of cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS), and mitogen-activated protein kinase (MAPK)/nuclear factor-κB (NF-κB) pathways. Our results indicate that HR1901-BS is a promising candidate as a functional material that enhances immune responses through macrophage activation.

(i) Background: The increasing prevalence of allergic diseases highlights the need for effective treatments. Lonicera caerulea fruit has been recognized for its anti-inflammatory, anti-cancer, and neuroprotective effects, but the mechanisms underlying its anti-allergic properties remain unclear. (ii) Objective: This study aims to evaluate the total phenolic, total flavonoid, and cyanidin-3-glucoside (C3G) contents of Lonicera caerulea extract (HR2302-30E) and to investigate its antioxidant and anti-allergic activities. (iii) Methods: Using an IgE-stimulated RBL-2H3 cell model, we assessed the effects of HR2302-30E and C3G on mast cell degranulation, β-hexosaminidase and histamine release. Western blot analysis was performed to evaluate the expression of high-affinity IgE receptor (FcεRI)β/γ and the phosphorylation of Src family kinases (Syk, Fyn). We also examined the phosphorylation of downstream factors phospholipase Cγ, protein kinase Cδ, and mitogen-activated protein kinase. (iv) Results: Total phenolic, flavonoid, and C3G contents of HR2302-30E were 18.73 mg GAE/g, 11.83 mg QE/g, and 7.02 mg/g, respectively. In IgE-activated mast cells, HR2302-30E and C3G inhibited β-hexosaminidase and histamine release. Western blot analysis revealed reduced expression of FcεRIβ/γ and decreased phosphorylation of key downstream signaling molecules. Conclusions: These findings suggest that HR2302-30E and C3G modulate FcεRI signaling, indicating their potential as natural anti-allergic agents.

The incidence of cardiovascular diseases, such as high blood pressure, is increasing worldwide, owing to population aging and irregular lifestyle habits. Previous studies have reported the vasorelaxant effects of Prunus yedoensis bark methanol extract. However, various solvent extracts of P. yedoensis bark and their vascular relaxation mechanisms have not been sufficiently studied. We prepared extracts of P. yedoensis bark using various solvents (water, 30% ethanol, and 70% ethanol). P. yedoensis bark 30% ethanol extract (PYB-30E) decreased the expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin in human umbilical vein endothelial cells (HUVECs) activated with 200 ng/mL TNF-α. Additionally, PYB-30E showed vasodilatory effects on isolated rat aortic rings. This was confirmed to be the result of the activation of the NO/cGMP pathway, regulation of non-selective calcium-activated K⁺ channels, and calcium channel blockade. Additionally, PYB-30E significantly reduced systolic and diastolic blood pressure in spontaneously hypertensive rats (SHR). Taken together, our results indicated that PYB-30E is a candidate functional material with preventive and therapeutic effects against hypertension.