scholarly journals The Cyclopentenone 15-Deoxy-Δ12,14-Prostaglandin J2 Delays Lipopolysaccharide-Induced Preterm Delivery and Reduces Mortality in the Newborn Mouse

Endocrinology ◽  
2009 ◽  
Vol 150 (2) ◽  
pp. 699-706 ◽  
Author(s):  
Grisha Pirianov ◽  
Simon N. Waddington ◽  
Tamsin M. Lindström ◽  
Vasiliki Terzidou ◽  
Huseyin Mehmet ◽  
...  

Intrauterine infection is a common trigger for preterm birth and is also a risk factor for the subsequent development of neurodevelopmental abnormalities in the neonate. Bacterial lipopolysaccharide (LPS) binds to toll-like receptor-4 (TLR-4) to activate proinflammatory signaling pathways, which are implicated in both preterm delivery and antenatal brain injury. The transcription factor nuclear factor-κB (NF-κB) is a key player in the orchestration of the inflammatory response and has a central role in parturition. Here we show that intrauterine administration of TLR-4-specific LPS to pregnant mice results in the activation of NF-κB in the maternal uterus and the fetal brain, up-regulation of proinflammatory proteins cyclooxygenase-2, chemokine ligand 1, ChemoKine (C-C motif) ligand 2, and cytosolic phospholipase A2 in myometrium, and induction of preterm delivery. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an antiinflammatory prostaglandin that plays a role in promoting the resolution of inflammation. We report that coadministration of 15d-PGJ2 and LPS to pregnant mice delays LPS-induced preterm delivery and confers protection from LPS-induced fetal mortality. This is associated with inhibition of myometrial NF-κB, cytosolic phospholipase A2, and c-Jun N-terminal kinase activation, and of inflammatory protein synthesis. Therefore 15d-PGJ2 has anti-inflammatory effects via inhibition of multiple aspects of inflammation-driven TRL-4 signaling pathway. Thus, 15d-PGJ2 or compounds with similar antiinflammatory functions may have potential as therapeutic agents in the management of preterm labor with the added advantage of preventing detrimental effects to the fetus that may result from infection/inflammation. Intrauterine lipopolysaccharide administration to pregnant mice activates nuclear factor-κ and Jun N-terminal kinase, causing preterm labor. 15-deoxy-Δ12,14-prostaglandin J2 inhibits this via multiple aspects of the toll-like receptor-4 signaling pathway.

2021 ◽  
Vol 19 (4) ◽  
pp. 432-437
Author(s):  
Lin Gao ◽  
Ming Yang ◽  
San Cai ◽  
Liping Gao ◽  
Chunfeng Gui ◽  
...  

Osteoarthritis is a progressive joint disease characterized by degeneration and destruction of articular cartilage. The incidence of osteoarthritis has increased steadily over the years leading to more than 50% in people over the age of 65. Due to associated side effects of prevailing therapeutics, better drugs are needed for osteoarthritis management. Asiaticoside is a bioactive component isolated from the medicinal plant Centella asiatica. It has been reported to possess neuroprotective, antiulcer, wound healing, anti-inflammatory, antioxidative, and other pharmacological properties. However, the potential of asiaticoside in the management of osteoarthritis remains to be explored. To this end, we examined the effect of asiaticoside on lipopolysaccharides induced inflammatory injury and apoptosis of chondrocytes. The results show that asiaticoside promotes viability and decrease in apoptosis of ATDC5 cells through decreased production of proinflammatory cytokines and the regulation of toll-like receptor 4/nuclear factor-kappa b signaling pathway. In summary, our results provide the evidence that asiaticoside could serve as a promising therapeutic drug for osteoarthritis treatment.


2021 ◽  
Vol 19 (3) ◽  
pp. 326-332
Author(s):  
Jinsi Tian ◽  
Xiaoya Xu ◽  
Da Tian

Traumatic brain injury refers to brain injury caused by mechanical impact often leading to severe morbidity and mortality. Despite increasing awareness, there are no effective treatments strategies. Therefore, there is a need to develop new effective treatments for this injury. Forsythiaside A is a monomer of phenylethanolglucoside extracted from Forsythia, which has a wide range of pharmacological properties including protective effects on brain tissue. Herein, using a rat model of traumatic brain injury, we have shown that forsythiaside A can improve nerve function and brain tissue injury in rats with traumatic brain injury, and reduce brain inflammation and neuronal apoptosis. We have further shown that forsythiaside A regulates toll-like receptor 4/myeloid differentiation factor 88/nuclear factor-kappa B signaling pathway. This opens the possibility of a potentially promising therapeutic drug for the treatment of traumatic brain injury.


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