Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

BACKGROUND:Studies have shown that both Panax notoginseng saponins and concentrated growth factor can promote fracture healing,but there are few studies addressing their combined effects on fracture healing.Panax notoginseng saponins may accelerate fracture healing by promoting the release of concentrated growth factor-related factors over a certain period of time. OBJECTIVE:To study the effect of Panax notoginseng saponins on concentrated growth factor release and fracture healing in rats. METHODS:Eighteen 8-week-old Sprague-Dawley rats were numbered and randomly divided into three groups:Panax notoginseng saponins group,model control group and blank group.Panax notoginseng saponins group was fed with Panax notoginseng saponins for 2 weeks.Model control group was given 2 mL of normal saline for 2 weeks and blank group was fed normally.Concentrated growth factor was obtained by the centrifugation method both from the Panax notoginseng saponins group and model control group.After 1 week of normal feeding,all animals underwent modeling for femoral fracture.The Panax notoginseng saponins group and the model control group were implanted with autologous concentrated growth factor,and then the release concentration of growth factors at different time points(1 hour,1,3,5,7,9 and 11 days)were measured by ELISA.Fracture healing was assessed based on postoperative X-ray and hematoxylin-eosin staining of bone tissues. RESULTS AND CONCLUSION:Compared with the model control group,the Panax notoginseng saponins group had higher release concentrations of vascular endothelial growth factor A and transforming growth factor β at 7,9,and 11 days,Platelet-derived growth factor BB at 5,9,and 11 days,and basic fibroblast growth factor at 1-11 days(P<0.01).X-ray examinations indicated that fracture healing in the Panax notoginseng saponins group was better than that in the model control group,and fracture healing in these two groups was better than that in the blank group at 2 months after surgery.Hematoxylin-eosin staining results found that the constituent osteocyte density in the Panax notoginseng saponins group was greater than that in the model control group,and the constituent osteocyte density in these two groups was better than that in the blank group.These findings indicate that Panax notoginseng saponins can increase the concentration of concentrated growth factor-related factors.After intervention with Panax notoginseng saponins,concentrated growth factors are more advantageous in promoting fracture healing in rats.