ArticleChinese medicine2023
Cyp4a12-mediated retinol metabolism in stellate cells is the antihepatic fibrosis mechanism of the Chinese medicine Fuzheng Huayu recipe.
Article in Chinese medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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9 citing papers in PubMed, 10 citations in OpenAlex.
- Longevity-driven hepatic transcriptional programs mediate resilience to diet-induced liver injury in Ames dwarf mice.GeroScience · 2026Article
- Ya-Jie-Sha-Ba Decoction Regulates Arachidonic Acid Metabolism to Treat Alcohol-Associated Liver Disease by Activating PPARα-CYP4A14 Axis: Insights From Multi-Omics Analysis and Experimental Validations.Journal of cellular and molecular medicine · 2026Article
- Fatty acid-activated proton transporter SR4 prevents hepatic steatosis and metabolic alterations in diabetic mice by improving mitochondria function, energy balance and oxidative stress.Experimental and therapeutic medicine · 2026Article
- Fuzheng Huayu tablets reduces the risk of further decompensation after the first decompensation in patients with HBV-related cirrhosis: protocol for a randomized, double-blind, placebo-controlled, multicenter trial.Frontiers in pharmacology · 2026Article
- Chinese Guidelines on the Management of Hepatic Encephalopathy in Cirrhosis (2024).Journal of clinical and translational hepatology · 2025Article
- Integrated evidence chain-based effectiveness evaluation of traditional Chinese medicines (Eff-iEC): A demonstration study.Acta pharmaceutica Sinica. B · 2025Article
- Bibliometrics-guided cyberpharmacology and transcriptomics for multidimensional analysis of the antihepatic fibrosis mechanism of kaempferol.Frontiers in molecular biosciences · 2025Article
- [Chinese guidelines on the management of hepatic encephalopathy in cirrhosis (2024)].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2024Article
- Macrophage cytotherapy on liver cirrhosis.Frontiers in pharmacology · 2023Review
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4 authors at 1 institution in 2 countries.
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Abstract
backgroundHepatic stellate cells (HSCs), which contain multiple retinol-containing lipid droplets, are important profibrotic cells in liver fibrosis. Under Cyp4a12a/b oxidation, HSC activation was accompanied by the downregulation of genes involved in retinol metabolism, inducing RAE-1 production. By eliminating activated HSCs, NK cells expressing the activating receptor NKG2D are recruited to alleviate fibrosis. FZHY was found to significantly reduce the severity of liver fibrosis by inhibiting the activation and proliferation of HSCs. The molecular processes that govern retinol metabolism, on the other hand, are largely unexplored. This study focused on the regulation of Cyp4a12a/b by FZHY to elucidate the antifibrotic molecular mechanisms underlying the effect of FZHY on retinol metabolism.
methodsTo investigate mechanisms and altered pathways of FZHY against carbon tetrachloride (CCl4)-induced liver fibrosis based on transcriptomics data. Bioinformatics analysis was used to screen its pharmacological targets. The predicted targets were confirmed by a series of in vitro and in vivo experiments, including mass spectrometry, in situ hybridization, immunofluorescence assays and real-time PCR. Then, the results were further characterized by recombinant adenovirus vectors that were constructed and transfected into the cultured primary HSCs.
resultsTranscriptomics revealed that Cyp4a12a/b is nearly completely lost in liver fibrosis, and these effects might be partially reversed by FZHY therapy recovery. In vitro and in vivo studies indicated that Cyp4a12a/b deletion disrupted retinol metabolism and lowered Rae-1 expression. Activated HSCs successfully escape recognition and elimination by natural killer (NK) cells as a result of reduced Rae-1. Notablely, we discovered that FZHY may restore the Cyp4a12a/b capability, allowing the recovery of the cytotoxic function of NK cells against HSCs, and thereby reducing hepatic fibrosis by suppressing HSC activation.
conclusionOur findings revealed a new role for Cyp4a in retinol metabolism in the development of hepatic fibrosis, and they highlight Cyp4a12/Rae-1 signals as possible therapeutic targets for antifibrotic medicines.
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