Andrographolide inhibits inflammatory responses in LPS-stimulated macrophages and murine acute colitis through activating AMPK.

Abstract

Andrographolide (Andro), a well-known labdane diterpenoid of Andrographis paniculata, has been reported to have anti-inflammatory effects in various inflammatory disease models. Despite ongoing efforts to elucidate the anti-inflammatory mechanism of Andro, its specific mechanism is not entirely clear. In this study, we confirmed the inhibitory effect of Andro on inflammatory activity and studied its mechanism in depth to find potential anti-inflammatory targets of Andro using lipopolysaccharide (LPS)-induced macrophages in vitro and a dextran sulfate sodium (DSS)-induced mouse model of acute colitis in vivo. We found that Andro significantly reduced proinflammatory cytokines by suppressing nuclear factor kappa B (NF-κB), mitogen-activated protein kinase (MAPK) and their upstream signaling pathways and activating the AMP activated protein kinase (AMPK) pathway in LPS-induced macrophages. Interestingly, Andro could not regulate the activation of the AMPK/NF-κB/MAPK pathway nor inhibit NF-κB and activator protein 1 (AP-1) nuclear translocation and nitric oxide (NO) production following knockdown of AMPKα2. Moreover, Andro attenuated DSS-induced intestinal barrier dysfunction and inflammation by suppressing the NF-κB and MAPK pathways in colon tissues while activating the AMPK pathway. In conclusion, our study demonstrates that Andro effectively inhibits LPS-induced inflammatory responses via AMPK activation in macrophages, whereby Andro can ameliorate DSS-induced acute colitis in mice.

• Authors: Nami Kim, Peeraphong Lertnimitphun, Yiwen Jiang, Hongsheng Tan, Hua Zhou, Yue Lu, Hongxi Xu
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 170 Pg. 113646 (12 2019) ISSN: 1873-2968 [Electronic] England
• PMID: 31545974 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Diterpenes
• Inflammation Mediators
• Lipopolysaccharides
• andrographolide
• AMP-Activated Protein Kinases

Topics

• AMP-Activated Protein Kinases (metabolism)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Cell Survival (drug effects, physiology)
• Colitis (drug therapy, metabolism)
• Diterpenes (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Humans
• Inflammation Mediators (antagonists & inhibitors, metabolism)
• Lipopolysaccharides (toxicity)
• Macrophages (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred BALB C
• RAW 264.7 Cells
• U937 Cells