Alkannin reverses lipopolysaccharides-induced inflammatory responses by suppressing mitogen-activated protein kinase and nuclear factor kappa-B signalling.

Abstract

Rheumatoid arthritis (RA) is an inflammatory disease that seriously affects human health worldwide. Meanwhile, inflammation in RAW264.7 cells could lead to the progression of RA. Alkannin (ALK) is derived from Alkanna tinctoria and is known to exert anti-tumor effects. However, the function of ALK in inflammation of RAW264.7 cells remains unclear. Thus, this research sought to investigate the detailed function of ALK in inflammatory responses of RAW264.7 cells. To induce an inflammatory response, RAW264.7 cells were exposed to lipopolysaccharide (LPS). MTT assay was applied to examine cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to assess the levels of inflammatory cytokines. Furthermore, the mechanism underlying ALK function in inflammatory responses was investigated using RT-qPCR and western blotting. The data revealed that LPS significantly increased the expression of cyclooxygenase 2 (COX-2), Interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and IL-6, whereas ALK reversed this effect. ALK also restored LPS-induced nuclear factor kappa-B (NF-κB) activation by inhibiting the downregulation of p-inhibitor kappa B alpha (IκBα). LPS elevated p-extracellular regulated protein kinases 1/2 (ERK1/2), phosphorylated p38 (p-p38), and phosphorylated -c-Jun N-terminal kinase (p-JNK) levels, which were markedly decreased in the presence of ALK. In summary, Alkannin attenuated LPS-induced inflammation by inhibiting NF-κB and MAPK signaling. Thus, our research might provide a new theoretical basis for exploring new strategies against RA.

• Authors: Jingya Yang, Jing Li, Lanzhu Yang, Ruohui Guo
• Journal: Bioengineered (Bioengineered) 2022 Jul-Dec Vol. 13 Issue 7-12 Pg. 14936-14946 ISSN: 2165-5987 [Electronic] United States
• PMID: 37105673 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• Mitogen-Activated Protein Kinases
• Lipopolysaccharides
• alkannin
• Anti-Inflammatory Agents
• Receptor Protein-Tyrosine Kinases
• Nitric Oxide
• Cyclooxygenase 2

Topics

• Humans
• NF-kappa B (metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• Lipopolysaccharides (adverse effects)
• Anti-Inflammatory Agents (pharmacology)
• Inflammation (metabolism)
• Receptor Protein-Tyrosine Kinases (metabolism, pharmacology, therapeutic use)
• Nitric Oxide (metabolism)
• Cyclooxygenase 2 (metabolism)
• MAP Kinase Signaling System