ArticleClinical and experimental immunology2016
The pharmacokinetics and dosing of oral 4-methylumbelliferone for inhibition of hyaluronan synthesis in mice.
Article in Clinical and experimental immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- Therapeutic potential of natural coumarins in autoimmune diseases with underlying mechanisms.Frontiers in immunology · 2024Pooled it
- Randomised, placebo-controlled trial of oral hymecromone in adults with pulmonary hypertension.Thorax · 2025Trial
- Oral hymecromone decreases hyaluronan in human study participants.The Journal of clinical investigation · 2022Trial
- Extracellular matrix remodeling therapeutic strategies to tackle central nervous system diseases.Neural regeneration research · 2026Article
- 4-methylumbelliferone attenuates amyloid pathology and learning deficits in the APP/PS1 mouse model.bioRxiv : the preprint server for biology · 2026Article
- Hyaluronan Regulates Vascular Smooth Muscle Cell Osteogenic Differentiation and Vascular Calcification.Biomolecules · 2026Article
- Hyaluronan in cardiac disease: implications for the extracellular matrix beyond collagen.American journal of physiology. Heart and circulatory physiology · 2026Review
- Hyaluronan Accumulates in Inflamed Lymph Nodes and Promotes B-Cell Activation.Proteoglycan research · 2025Article
- Beneficial Actions of 4-Methylumbelliferone in Type 1 Diabetes by Promoting β Cell Renewal and Inhibiting Dedifferentiation.Biomedicines · 2024Article
- Article
- Inhibition of hyaluronan synthesis prevents β-cell loss in obesity-associated type 2 diabetes.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Hyaluronan synthesis inhibition normalizes ethanol-enhanced hepatic stellate cell activation.Alcohol, clinical & experimental research · 2023Article
- 4-Methylumbeliferone Treatment at a Dose of 1.2 g/kg/Day Is Safe for Long-Term Usage in Rats.International journal of molecular sciences · 2023Article
- Hyaluronan in the pathogenesis of acute and post-acute COVID-19 infection.Matrix biology : journal of the International Society for Matrix Biology · 2023Review
- 3'UTR shortening of HAS2 promotes hyaluronan hyper-synthesis and bioenergetic dysfunction in pulmonary hypertension.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Targeting UDP-α-d-glucose 6-dehydrogenase alters the CNS tumor immune microenvironment and inhibits glioblastoma growth.Genes & diseases · 2022Article
- Modulation of hyaluronan signaling as a therapeutic target in human disease.Pharmacology & therapeutics · 2022Review
- Oral treatment of 4-methylumbelliferone reduced perineuronal nets and improved recognition memory in mice.Brain research bulletin · 2022Article
- Plant-Derived Molecule 4-Methylumbelliferone Suppresses FcεRI-Mediated Mast Cell Activation and Allergic Inflammation.Molecules (Basel, Switzerland) · 2022Article
- Skin-specific knockdown of hyaluronan in mice by an optimized topical 4-methylumbelliferone formulation.Drug delivery · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Recently, there has been considerable interest in using 4-methylumbelliferone (4-MU) to inhibit hyaluronan (HA) synthesis in mouse models of cancer, autoimmunity and a variety of other inflammatory disorders where HA has been implicated in disease pathogenesis. In order to facilitate future studies in this area, we have examined the dosing, treatment route, treatment duration and metabolism of 4-MU in both C57BL/6 and BALB/c mice. Mice fed chow containing 5% 4-MU, a dose calculated to deliver 250 mg/mouse/day, initially lose substantial weight but typically resume normal weight gain after 1 week. It also takes up to a week to see a reduction in serum HA in these animals, indicating that at least a 1-week loading period on the drug is required for most protocols. At steady state, more than 90% of the drug is present in plasma as the glucuronidated metabolite 4-methylumbelliferyl glucuronide (4-MUG), with the sulphated metabolite, 4-methylumbelliferyl sulphate (4-MUS) comprising most of the remainder. Chow containing 5% but not 0·65% 4-MU was effective at preventing disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, as well as in the DORmO mouse model of autoimmune diabetes. While oral 4-MU was effective at preventing EAE, daily intraperitoneal injections of 4-MU were not. Factors potentially affecting 4-MU uptake and plasma concentrations in mice include its taste, short half-life and low bioavailability. These studies provide a practical resource for implementing oral 4-MU treatment protocols in mice.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.