Reviving peroxisome proliferator-activated receptors in fatty liver disease: From herbal formula to nuclear receptor targeting

Bibliographic Information
Authors: Fouad Y.; Said E.M.; Kamani L.; El-Khayat H.R.
Journal: World Journal of Gastroenterology
Publisher: Baishideng Publishing Group Inc
Publication Date: 21 September 2026
Volume / Issue: Volume 32 / Issue 35
Article No.: 119168
ISSN: 10079327
DOI: 10.3748/wjg.119168
Scopus: View on Scopus
Document Type: Review
Access: All Open Access; Hybrid Gold Open Access
Authors and Affiliations
Fouad Y., Department of Gastroenterology and Endemic Medicine, Faculty of Medicine Minia University, Minia, 19111, Egypt; Said E.M., Department of Hepatology, Gastroenterology and Infectious Diseases, Faculty of Medicine, Benha University, Benha, 13518, Egypt; Kamani L., Department of Medicine, Aga Khan University Hospital, Sindh, Karachi, 14322, Pakistan; El-Khayat H.R., Department of Gastroenterology and Endemic Medicine, Theodore Research Institute, Cairo, 23323, Egypt
Abstract
Due in large part to its intricate metabolic and inflammatory pathogenesis, metabolic dysfunction-associated fatty liver disease (MAFLD), the most common chronic liver disease in the world, still lacks a widely effective pharmacological treatment. Present mechanistic evidence that Lianhe Xiaozhi ointment (LXO), a formulation derived from traditional Chinese medicine, improves MAFLD by coordinating the activation of peroxisome proliferator-activated receptor alpha (PPARα). The authors show that LXO increases hepatic fatty acid oxidation and ketogenesis while inhibiting inflammatory signaling using an integrated systems approach that combines network pharmacology, hepatic transcriptomics, experimental models, and gut microbiota profiling. Significantly, LXO links intestinal metabolism to hepatic metabolic control by altering the gut microbiota and increasing endogenous fatty acid ligands, which further activate PPARα. In addition to repositioning PPARα as a key metabolic-immune hub, this study shows how multicomponent therapies may be able to overcome the drawbacks of single-target approaches in the treatment of MAFLD. © 2026 Baishideng Publishing Group Inc. All rights reserved.
Keywords
Fatty acid oxidation; Inflammation; Metabolic dysfunction-associated steatotic liver disease; Peroxisome proliferator-activated receptor alpha; Traditional Chinese; cell nucleus receptor; fatty acid; peroxisome proliferator activated receptor; peroxisome proliferator activated receptor alpha; animal experiment; animal model; Chinese medicine; clinical article; controlled study; drug combination; drug comparison; drug therapy; fatty liver; human; intestine flora; ketogenesis; liver; liver disease; male; metabolic disorder; metabolic fatty liver; metabolic regulation; nonhuman; ointment; pharmacology; review; signal transduction; systems pharmacology; transcriptomics
Citation Information
Scopus Citations: 0
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