Lucidone inhibits iNOS and COX-2 expression in LPS-induced RAW 264.7 murine macrophage cells via NF-κB and MAPKs dual pathways

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
S Kumar ◽  
K Jayabal ◽  
SY Wang
2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Amy Seewald ◽  
Fatima Pina ◽  
Kandice Beverly ◽  
Brenda Jane Smith ◽  
Edralin Lucas

Processes ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 2062
Author(s):  
Thuy Thi Trinh ◽  
Ailyn Fadriquela ◽  
Johny Bajgai ◽  
Subham Sharma ◽  
Md. Habibur Rahman ◽  
...  

Excessive oxidative stress (OS) is a common cause of various diseases such as cancer, diabetes, and obesity; thus, an anti-oxidative solution is essential for the improvement of human health. Increasing evidence suggests that alkaline reduced water (ARW), especially between pH 9.5–10.0, has antioxidant capacity; however, relatively few studies have reported the effect of weak ARW at pH 8.5 on OS, especially in vitro. This study was conducted to evaluate the anti-oxidative efficacy of weak ARW with negative oxidation-reduction potential (ORP) and relatively high hydrogen (H2) concentration, as compared to tap water (TW) and ARW at pH 9.5. RAW 264.7 murine macrophage cells, stimulated by hydrogen peroxide (H2O2) and lipopolysaccharide (LPS) to induce OS, were used as a control (Con) and then treated with TW and ARW at pH 8.5 (ARW_8.5) and pH 9.5 (ARW_9.5) at different concentrations (0.1%, 1%, and 10% v/v). Results showed that cell viability was significantly restored after treatment with both ARW_8.5 and ARW_9.5 compared to Con/H2O2 and Con/LPS, while TW treatment did not induce significant changes. Levels of reactive oxygen species (ROS), nitric oxide (NO), Ca2+, catalase, and glutathione peroxide (GPx) showed significant differences in a concentration-dependent manner in ARW_8.5 and ARW_9.5 groups compared to Con/H2O2 and Con/LPS groups. Likewise, the expression of p-p38, p-JNK, and p-ERK was also significantly reduced in the ARW-treated groups, but not in the TW group. In conclusion, ARW_8.5 exhibited anti-oxidative effects through the regulation of the MAPK signaling pathway in RAW 264.7 murine macrophage cells, indicating the health-promoting potential of weak ARW through daily intake.


Author(s):  
Lenisa Dandara dos Santos ◽  
Thamires Quadros Froes ◽  
Miriam Cristina Contin de Melo ◽  
Gloria Emília Petto de Souza ◽  
Denis de Melo Soares ◽  
...  

Background:: Microsomal prostaglandin E synthase-1 (mPGES-1) catalyzes the terminal step of prostaglandin E2 (PGE2) production, which plays an important role in the regulation of febrile response. In our previous work, ligand-based pharmacophore models, built with mPGES-1 inhibitors, were employed to identify a novel series of compounds that reduce the febrile response in rats. Objectives:: Evaluate the mechanism of action of the most active compound (1). Methods:: For in vivo assays, rats were pretreated with the antipyretic compounds 1-8, 30 min before LPS injection. For in vitro assays, RAW 264.7 macrophage cells were incubated with the antipyretic compounds 1-8 for 1 hour before LPS stimu-lus. After 16 h, quantitative real-time PCR was carried out. Additionally, the PGE2 concentration in hypothalamus was quantified by ELISA and the inhibitory effect of N-cyclopentyl-N'-[3-(3-cyclopropyl-1H-1,2,4-triazol-5-yl)phenyl]ethanediamide (1) over human COX-2 enzymatic activity was determined with a COX Colorimetric Inhibitor Screening Assay Kit. Results:: Compound 1 and CAY10526 have comparable efficacy to reduce the febrile response when injected i.v. (com-pound 1: 63.10%, CAY10526: 70.20%). Moreover, compound 1 significantly reduces the mPGES-1 mRNA levels, in RAW264.7 cells, under inflammatory conditions. A chemically-similar compound (8- ) also significantly reduces the mRNA levels of the gene target. On the other hand, compounds 6 and 7, which are also somewhat similar to compound 1, do not, significantly, impact mPGES-1 mRNA levels. Conclusions:: PGE2 concentration reduction in hypothalamus, due to compound 1 central injection, is related to decreased mPGES-1 mRNA levels but not to COX-2 inhibition (IC50> 50 μM). Therefore, compound 1 is a promising lead for inno-vative antipyretic drug development.


2009 ◽  
Vol 25 (2) ◽  
pp. 240-246 ◽  
Author(s):  
Dong Hee Lee ◽  
Na Ryoung Kim ◽  
Bum-Soon Lim ◽  
Yong-Keun Lee ◽  
Hyeong-Cheol Yang

Sign in / Sign up

Export Citation Format

Share Document