Pharmacology of bioactive compounds from plant extracts for improving non-alcoholic fatty liver disease through endoplasmic reticulum stress modulation: A comprehensive review

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver condition with significant clinical implications. Emerging research indicates endoplasmic reticulum (ER) stress as a critical pathogenic factor governing inflammatory responses, lipid metabolism and insulin signal transduction in patients with NAFLD. ER stress-associated activation of multiple signal transduction pathways, including the unfolded protein response, disrupts lipid homeostasis and substantially contributes to NAFLD development and progression. Targeting ER stress for liver function enhancement presents an innovative therapeutic strategy. Notably, the natural bioactive compounds of plant extracts have shown potential for treating NAFLD by reducing the level of ER stress marker proteins and mitigating inflammation, stress responses, and de novo lipogenesis. However, owing to limited comprehensive reviews, the effectiveness and pharmacology of these bioactive compounds remain uncertain. Objectives: To address the abovementioned challenges, the current review categorizes the bioactive compounds of plant extracts by chemical structures and properties into flavonoids, phenols, terpenoids, glycosides, lipids and quinones and examines their ameliorative potential for NAFLD under ER stress. Methods: This review systematically analyses the literature on the interactions of bioactive compounds from plant extracts with molecular targets under ER stress, providing a holistic view of NAFLD therapy. Results: Bioactive compounds from plant extracts may improve NAFLD by alleviating ER stress; reducing lipid synthesis, inflammation, oxidative stress and apoptosis and enhancing fatty acid metabolism. This provides a multifaceted approach for treating NAFLD. Conclusion: This review underscores the role of ER stress in NAFLD and the potential of plant bioactive compounds in treating this condition. The molecular mechanisms by which plant bioactive compounds interact with their ER stress targets provide a basis for further exploration in NAFLD management.