2. Academic Validation
  3. Nargenicin A1 attenuates lipopolysaccharide-induced inflammatory and oxidative response by blocking the NF-κB signaling pathway

Nargenicin A1 attenuates lipopolysaccharide-induced inflammatory and oxidative response by blocking the NF-κB signaling pathway

  • EXCLI J. 2021 May 28:20:968-982. doi: 10.17179/excli2021-3506.
Da Hye Kwon 1 2,  Gi-Young Kim 3,  Hee-Jae Cha 4,  Suhkmann Kim 5,  Heui-Soo Kim 6,  Hye-Jin Hwang 7,  Yung Hyun Choi 1 2
Affiliations

Affiliations

  • 1 Anti-Aging Research Center, Dong-eui University, Busan, Republic of Korea.
  • 2 Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, Republic of Korea.
  • 3 Department of Marine Life Science, School of Marine Biomedical Sciences, Jeju National University, Jeju, Republic of Korea.
  • 4 Department of Parasitology and Genetics, College of Medicine, Kosin University, Busan, Republic of Korea.
  • 5 Department of Chemistry, College of Natural Sciences, Pusan National University, Busan, Republic of Korea.
  • 6 Department of Biological Sciences, College of Natural Sciences, Pusan National University, Busan, Republic of Korea.
  • 7 Department of Food and Nutrition, College of Nursing, Healthcare Sciences & Human Ecology, Dong-eui University, Busan, Republic of Korea.
PMID: 34267609 DOI: 10.17179/excli2021-3506
Abstract

Inflammation caused by the excessive production of pro-inflammatory mediators and cytokines in abnormally activated macrophages promotes the initiation and progression of many diseases along with oxidative stress. Previous studies have suggested that nargenicin A1, an Antibacterial macrolide isolated from Nocardia sp. may be a potential treatment for inflammatory responses and oxidative stress, but the detailed mechanisms are still not well studied. In this study, we investigated the inhibitory effect of nargenicin A1 on inflammatory and oxidative stress in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish (Danio rerio) models. Our results indicated that nargenicin A1 treatment significantly inhibited LPS-induced release of pro-inflammatory mediators including nitric oxide (NO) and prostaglandin E2, which was associated with decreased inducible NO Synthase and cyclooxygenase-2 expression. In addition, nargenicin A1 attenuated the LPS-induced expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and monocyte chemotactic protein-1, reducing their extracellular secretion. Nargenicin A1 also suppressed LPS-induced generation of Reactive Oxygen Species. Moreover, nargenicin A1 abolished the LPS-mediated nuclear translocation of nuclear factor-kappa B (NF-κB) and the degradation of inhibitor IκB-α, indicating that nargenicin A1 exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. Furthermore, nargenicin A1 showed strong protective effects against NO and ROS production in LPS-injected zebrafish larvae. In conclusion, our findings suggest that nargenicin A1 ameliorates LPS-induced anti-inflammatory and antioxidant effects by downregulating the NF-κB signaling pathway, and that nargenicin A1 can be a potential functional agent to prevent inflammatory- and oxidative-mediated damage.

Keywords

NF-kappaB; ROS; inflammation; nargenicin A1.

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