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

Theodor Bilharz Research Institute

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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