AMPK Signalling Pathway: A Potential Strategy for the Treatment of Heart Failure with Chinese Medicine

Abstract

Heart failure (HF) is a complex clinical syndrome that represents the advanced stage of cardiovascular disease, characterized by systolic and diastolic dysfunction of the heart. Despite continuous updates in HF treatment drugs, the morbidity and mortality rates remain high, necessitating ongoing exploration for new therapeutic targets. Adenosine monophosphate-activated protein kinase (AMPK) is the serine/ threonine protein kinase which responds to adenosine monophosphate (AMP) levels.Activation of AMPK shifts cellular metabolic patterns from synthesis to catabolism, enhancing energy metabolism in pathological conditions such as inflammation, ischemia, obesity, and aging. Numerous studies have identified AMPK as a vital target for HF treatment, with herbal monomers/extracts and compounds affecting key signaling factors including rapamycin targeting protein (mTOR), silencing regulator protein 1 (SIRT1), nuclear transcription factor E2-related factor 2 (Nrf2), and nuclear transcription factor-κB (NF-κB) through regulation of the AMPK signaling pathway.This modulation can achieve the effects of improving metabolism, autophagy, reducing oxidative stress and inflammatory response in the treatment of heart failure, with the advantages of multi-targeting, comprehensive action and low toxicity.The modulation of the AMPK pathway by Traditional Chinese Medicine (TCM) has emerged as a crucial research direction for the prevention and treatment of HF, but a systematic summary and generalization in this field is lacking. This article provides an overview of the composition, regulation, and mechanism of the AMPK signaling pathway's influence on HF, as well as a summary of current research on the regulation of the AMPK pathway by TCM for HF prevention and treatment. The aim is to serve as a reference for the diagnosis and treatment of HF using TCM and the development of new drugs.

The signaling pathways of selected traditional Chinese medicine prescriptions and their metabolites in the treatment of diabetic cardiomyopathy: a review

“…In addition, AMPK can improve DCM by regulating glycolipid metabolism, regulating protein synthesis and degradation, affecting the transcription of proteins related to gluconeogenesis, lipogenesis, and mitochondrial biogenesis, and regulating vascular endothelial dysfunction. Therefore, AMPK is a potential therapeutic target for DCM ( Nellaiappan et al, 2019 ; Peng et al, 2022 ; Entezari et al, 2022 ; Liu et al, 2023 ).…”

Modulation of atherosclerosis‐related signaling pathways by Chinese herbal extracts: Recent evidence and perspectives

“…Chinese medicine extracts, derived from single Chinese medicines and further isolated and purified, offer the benefits of high efficiency and low toxicity (Hu et al, 2021; Zhang, Lin, & Ye, 2018), gaining prominence in AS prevention and treatment research due to their well‐defined active ingredients and ease of dosage precision (Junren et al, 2021). An increasing number of domestic and international researchers have undertaken ex vivo and in vivo studies to investigate the mechanisms of action of active components in single herbs (Liu, Guo, et al, 2023; Liu, Tan, et al, 2023). This article aims to explore the relevant signal transduction pathways crucial to the pathological formation of AS and the mechanisms by which herbal extracts combat AS.…”

Xinbao Pill ameliorates heart failure via regulating the SGLT1/AMPK/PPARα axis to improve myocardial fatty acid energy metabolism

“…Currently, novel strategies have emerged in managing HF that focus on increasing energy supply and counteracting metabolic remodelling [ 5 , 6 ]. Numerous studies have proven that activation of the AMPK/PPARα signalling pathway prevents the development of HF by increasing cardiac fatty acid metabolism [ 7 ]. AMPK acts as a “switch” of cellular energy metabolism, capable of self-activation in response to changes in the intracellular AMP/ATP ratio [ 8 ].…”