Natural Products Ameliorate Non-Alcoholic Fatty Liver Disease and Atherosclerosis via the LKB1/AMPK Pathway

Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis (AS) are two major phenotypes of metabolic syndrome that frequently coexist through a “liver–vascular axis” characterized by lipid dysregulation, chronic inflammation, and mitochondrial dysfunction. The liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) signaling pathway, acting as a master regulator of energy and redox balance, has emerged as a central hub in this comorbidity. Activation of this pathway suppresses lipogenesis, enhances fatty acid oxidation, attenuates inflammation, and improves endothelial function, thereby interrupting the vicious metabolic–inflammatory cycle underlying NAFLD and AS. Natural products provide promising multi-target modulators of LKB1/AMPK. Polyphenols (such as curcumin, resveratrol, quercetin), terpenoids (such as nobiletin, betulinic acid), alkaloids (such as berberine), and glycosides (such as ginsenosides, salidroside) restore lipid homeostasis, induce autophagy, regulate oxidative stress, and modulate immune responses via LKB1/AMPK and its crosstalk with sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α), and mammalian target of rapamycin (mTOR) signaling. Preclinical studies highlight their ability to improve hepatic steatosis, vascular inflammation, and plaque stability, underscoring their cross-organ therapeutic potential. However, pharmacological translation remains limited by poor bioavailability, variable pharmacokinetics, species differences, and inconsistent clinical outcomes. This review systematically summarizes comorbidity mechanisms of NAFLD and AS, regulatory roles of the LKB1/AMPK pathway, therapeutic actions of representative natural products, and the challenges ahead, aiming to guide precision strategies for metabolic syndromes.

• Publication year

  2025

• Venue

  Natural Product Communications

• Publication date

  2025-11-01

• Fields of study

  Not labeled

• Identifiers
  DOI 10.1177/1934578X251394620
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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