Natural AMPK Activators in Cardiovascular Disease Prevention

Abstract

Cardiovascular diseases (CVD), as a life-threatening global disease, is receiving worldwide attention. Seeking novel therapeutic strategies and agents is of utmost importance to curb CVD. AMP-activated protein kinase (AMPK) activators derived from natural products are promising agents for cardiovascular drug development owning to regulatory effects on physiological processes and diverse cardiometabolic disorders. In the past decade, different therapeutic agents from natural products and herbal medicines have been explored as good templates of AMPK activators. Hereby, we overviewed the role of AMPK signaling in the cardiovascular system, as well as evidence implicating AMPK activators as potential therapeutic tools. In the present review, efforts have been made to compile and update relevant information from both preclinical and clinical studies, which investigated the role of natural products as AMPK activators in cardiovascular therapeutics.

Methotrexate and cardiovascular prevention: an appraisal of the current evidence

“…[204][205][206][207][208][209][210][211] Furthermore, AMPK exerts beneficial effects on glucose homeostasis by stimulating cellular glucose uptake and glycolysis. [212][213][214] Redox balance Methotrexate has been traditionally used at high doses to induce cytotoxicity in the treatment of malignancies as well as in experimental studies investigating the effects of rescuing treatments. The cytotoxic effects of methotrexate are ascribed to the inhibition of dihydrofolate reductase, involved in the conversion of dihydrofolate into tetrahydrofolate, required for the synthesis of the nucleotides of both DNA and RNA and the de novo purine synthesis of both purine and thymidylate synthase, which further inhibits DNA synthesis (Figure 1).…”

Vascular homeostasis in atherosclerosis: A holistic overview

“…To this end, several categories of drugs are able to stabilize the “vascular niche” ( 51 ) and prevent atherosclerosis ( Figure 2B ). These drugs include statins (lipid-lowering drugs) ( 52 ), Angptl3 inhibitors ( 53 ), ACLY inhibitors (such as Bempedoic acid) ( 54 ), gliflozins (SGLT2 inhibitors, anti-diabetic drugs) ( 55 ), glutides (GLP-1 receptor agonists, anti-diabetic drugs) ( 56 ), metformin (anti-diabetic drugs) ( 57 – 59 ), aspirin (COX inhibitor, NSAIDs), Angiotensin II converting enzyme inhibitors (ACEI, anti-hypertensive drugs) ( 60 ), Angiotensin II receptor blockers (ARBs, anti-hypertensive drugs) ( 60 , 61 ), naturally-occurring NLRP3 inflammasome inhibitor (colchicine) ( 62 ), KLF2 activators ( 63 , 64 ), AMPK activators (endothelial protective drugs) ( 65 ) and many others. Based on the complex nature of atherosclerosis, polypill or ploypharmacology targeting established mechanisms/risk factors are needed.…”

Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals using in silico prospective screening approaches

“…In 2019, CVDs are clearly considered as a major health complication that causes 17.9 million deaths worldwide. By 2030, the expected deaths of CVDs will increase to 24 million people per year worldwide ( Moghaddam et al, 2022 ). Atherosclerosis, a chronic vascular inflammatory disorder, is clearly introduced as steroid plaques that result from a deposition of low density lipoprotein-cholesterol (LDL-c) on the walls of coronary arteries due to hypercholesterolemia.…”