5’AMP-activated protein kinase: an emerging target of phytochemicals to treat chronic inflammatory diseases

Abstract

Inflammation is a defensive response of the organism to traumatic, infectious, toxic, ischemic, and autoimmune injury. Inflammatory mediators are released to effectively eliminate the inflammatory trigger and restore homeostasis. However, failure of these processes can lead to chronic inflammatory conditions and diseases such as inflammatory bowel diseases, rheumatoid arthritis, inflammatory lung diseases, atherosclerosis, and neurodegenerative diseases. The cure of chronic inflammatory diseases remains challenging as current therapies have various limitations, such as pronounced side effects, progressive loss of efficacy, and high cost especially for biologics. In this context, phytochemicals (such as alkaloids, flavonoids, lignans, phenolic acids, saponins, terpenoids, and other classes) are considered as an interesting alternative approach. Among the numerous targets of phytochemicals, AMP-activated protein kinase (AMPK) can be considered as an interesting target in the context of inflammation. AMPK regulates inflammatory response by inhibiting inflammatory pathways (NF-κB, JAK/STAT, and MAPK) and regulating several other processes of the inflammatory response (oxidative stress, autophagy, and apoptosis). In this review, we summarize and discuss the studies focusing on phytochemicals that showed beneficial effects by blocking different inflammatory pathways implicating AMPK activation in chronic inflammatory disease models. We also highlight elements to consider when investigating AMPK in the context of phytochemicals.

Keywords:

• Dorsomorphin
• curcuminoids
• stilbenoids
• AICAR
• ARDS
• acute lung injury

Acknowledgements

The authors gratefully acknowledge Higher Education Commission, Pakistan for financial support under the project “Faculty Development Program of Bahauddin Zakariya University Multan (100 PhD foreign scholarships) (Prime Minister’s directive)”. M.A. is a research associate from the FRS-FNRS (Fonds de la Recherche Scientifique) Belgium.

Disclosure statement

The authors have no conflict of interest to declare.

Additional information

Funding

Funding (to HAK) was provided by Higher Education Commission, Pakistan under the project “Faculty Development Program of Bahauddin Zakariya University Multan (100 PhD foreign scholarships) (Prime Minister’s directive)”.