Anti-Inflammatory Mechanism of An Alkaloid Rutaecarpine in LTA-Stimulated RAW 264.7 Cells: Pivotal Role on NF-κB and ERK/p38 Signaling Molecules.

Abstract

Lipoteichoic acid (LTA) is a key cell wall component and virulence factor of Gram-positive bacteria. LTA contributes a major role in infection and it mediates inflammatory responses in the host. Rutaecarpine, an indolopyridoquinazolinone alkaloid isolated from Evodia rutaecarpa, has shown a variety of fascinating biological properties such as anti-thrombotic, anticancer, anti-obesity and thermoregulatory, vasorelaxing activity. It has also potent effects on the cardiovascular and endocrine systems. Herein, we investigated rutaecarpine's (Rut) anti-inflammatory effects in LTA-stimulated RAW macrophage cells. The Western blot and spectrophotometric results revealed that Rut inhibited the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1β in the LTA-induced macrophage cells. Successively, our mechanistic studies publicized that Rut inhibited LTA-induced phosphorylation of mitogen-activated protein kinase (MAPK) including the extracellular signal-regulated kinase (ERK), and p38, but not c-Jun NH2-terminal kinase (JNK). In addition, the respective Western blot and confocal image analyses exhibited that Rut reserved nuclear transcription factor kappa-B (NF-κB) by hindering inhibitor of nuclear factor κB-α (IκBα) and NF-κB p65 phosphorylation and p65 nuclear translocation. These results indicate that Rut exhibits its anti-inflammatory effects mainly through attenuating NF-κB and ERK/p38 signaling pathways. Overall, this result suggests that Rut could be a potential therapeutic agent for the treatment of Gram-positive bacteria induced inflammatory diseases.

• Authors: Thanasekaran Jayakumar, Chun-Ming Yang, Ting-Lin Yen, Chia-Yuan Hsu, Joen-Rong Sheu, Chih-Wei Hsia, Manjunath Manubolu, Wei-Chieh Huang, Cheng-Ying Hsieh, Chih-Hsuan Hsia
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 23 Issue 11 (May 24 2022) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 35682568 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Indole Alkaloids
• Lipopolysaccharides
• NF-kappa B
• Quinazolines
• Teichoic Acids
• Nitric Oxide
• lipoteichoic acid
• rutecarpine
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2
• Extracellular Signal-Regulated MAP Kinases
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Cyclooxygenase 2 (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Indole Alkaloids (pharmacology)
• Lipopolysaccharides (pharmacology)
• Mice
• NF-kappa B (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Quinazolines
• RAW 264.7 Cells
• Teichoic Acids
• p38 Mitogen-Activated Protein Kinases (metabolism)