Abietic acid attenuates sepsis-induced lung injury by inhibiting nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway to inhibit M1 macrophage polarization.

Abstract

Lung injury is one of the leading causes of death in sepsis. Abietic acid (AA) has demonstrated anti-inflammatory and bacteriostatic properties. Herein, we established a mouse model of sepsis by cecal ligation and puncture, and intraperitoneally injected AA to treat. Lung injury was assessed by H&E staining and the inflammation in bronchoalveolar lavage fluid (BALF) were assessed by counting the number of inflammatory cells and detecting the content of inflammatory factors. Meanwhile, we also designed to study the effect of AA on lipopolysaccharide (LPS)-induced inflammatory response and macrophage marker gene expression in RAW264.7 cells in vitro. In this study, we found that AA inhibited LPS-induced secretion of inflammatory mediators (IL-1β, TNF-α, IL-6 and MIP-2), and decreased the expression of M1 macrophage e markers (CD16 and iNOS) and p-p65 protein, while increased the expression of M2 macrophage markers (CD206 and Arg-1) in RAW264.7 cells in vitro. In vivo, the therapy of AA not only rescued septic animals, but also attenuated lung injury in sepsis mice. Moreover, AA decreased the number of total cells, neutrophils and macrophages, the conceration of total protein, and the levels of inflammatory mediators in BALF of sepsis mice. Further, we found that AA inhibited M1 macrophage polarization and blocked nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway in BALF of sepsis mice. In conclusion, Abietic acid attenuates sepsis-induced lung injury, and its mechanism may be related to reducing inflammation by inhibiting NF-κB signaling to inhibit M1 macrophage polarization.

• Authors: Honglong Fang, Juan Chen, Jian Luo, Jianhua Hu, Danqiong Wang, Liang Lv, Weiwen Zhang
• Journal: Experimental animals (Exp Anim) Vol. 71 Issue 4 Pg. 481-490 (Nov 10 2022) ISSN: 1881-7122 [Electronic] Japan
• PMID: 35644586 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• Lipopolysaccharides
• abietic acid
• Inflammation Mediators

Topics

• Mice
• Animals
• NF-kappa B (metabolism)
• Lipopolysaccharides (adverse effects)
• Macrophages (metabolism)
• Sepsis (complications, drug therapy)
• Acute Lung Injury (etiology, chemically induced)
• Inflammation Mediators (metabolism)
• Inflammation