Journal
INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY
Volume 36, Issue -, Pages -Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/03946320221133017
Keywords
niloticin; anti-inflammatory activity; myeloid differentiation protein 2; mechanism
Categories
Funding
- National Natural Science Foundation of China [81303205, 81803681]
- intercollegiate joint training program of colleges and universities in Liaoning Province and Scientific research project of Liaoning Provincial Department of Education [LJKZ0897]
Ask authors/readers for more resources
This study evaluated the potential therapeutic effects of Niloticin and its ability to bind to MD-2, a protein involved in inflammatory responses mediated by TLR4. The results showed that Niloticin could significantly decrease the levels of inflammatory cytokines induced by LPS and inhibit the activation of the LPS-TLR4/MD-2-NF-kappa B signaling pathway.
Objectives Niloticin is an active compound isolated from Cortex phellodendri with uncharacterized anti-inflammatory activity. We assessed the drug potential of niloticin and examined its ability to target myeloid differentiation protein 2 (MD-2) to ascertain the mechanism for its anti-inflammatory activity. Methods The Traditional Chinese Medicine Systems Pharmacology Database was used to evaluate niloticin. Bio-layer interferometry and molecular docking technologies were used to explore how niloticin targets MD-2, which mediates a series of toll-like receptor 4 (TLR4)-dependent inflammatory responses. The cytokines involved in the lipopolysaccharide (LPS)-TLR4/MD-2-NF-kappa B pathway were evaluated using ELISA, RT-qPCR, and western blotting. Results Niloticin could bind to MD-2 and had no evident effects on cell viability. Niloticin treatment significantly decreased the levels of NO, IL-6, TNF-alpha, and IL-1 beta induced by LPS (p < 0.01). IL-1 beta, IL-6, iNOS, TNF-alpha, and COX-2 mRNA expression levels were decreased by niloticin (all p < 0.01). Compared with that in the control group, the increase in TLR4, p65, MyD88, p-p65, and iNOS expression levels induced by LPS were suppressed by niloticin (all p < 0.01). Conclusion Our results suggest that niloticin has therapeutic potential and binds to MD-2. Niloticin binding to MD-2 antagonized the effects of LPS binding to the TLR4/MD-2 complex, resulting in the inhibition of the LPS-TLR4/MD-2-NF-kappa B signaling pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available