ArticleArthritis research & therapy2018
Arhalofenate acid inhibits monosodium urate crystal-induced inflammatory responses through activation of AMP-activated protein kinase (AMPK) signaling.
Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 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
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Systematic review of the subcutaneous air pouch model using monosodium urate and calcium pyrophosphate and recommendations for studying crystal-related arthropathies.Animal models and experimental medicine · 2025Pooled it
- From soluble uric acid to sodium urate crystal: immune metabolic inflammation driven by uric acid morphological transformation and mechanism-oriented therapy.Frontiers in immunology · 2026Review
- Gout and NLRP3 Inflammasome Biology.Arthritis & rheumatology (Hoboken, N.J.) · 2025Review
- Follow the Molecule from Crystal Arthropathy to Comorbidities: The 2024 G-CAN Gold Medal Award Awardee Lecture.Gout, urate, and crystal deposition disease · 2025Article
- The Role of Autophagy in HIV Infection and Immunological Recovery of ART-Treated PLWH.Viruses · 2025Review
- Alcohol promotes CPT1A-induced lipid metabolism disorder to sentinel-regulate acute pancreatitis.European journal of medical research · 2025Article
- ML335 inhibits TWIK2 channel-mediated potassium efflux and attenuates mitochondrial damage in MSU crystal-induced inflammation.Journal of translational medicine · 2024Article
- Mechanism of Reactive Oxygen Species-Guided Immune Responses in Gouty Arthritis and Potential Therapeutic Targets.Biomolecules · 2024Review
- The NADase CD38 is a central regulator in gouty inflammation and a novel druggable therapeutic target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- The Evolving Landscape of Gout in the Female: A Narrative Review.Gout, urate, and crystal deposition disease · 2023Article
- Ozone alleviates MSU-induced acute gout pain via upregulating AMPK/GAS6/MerTK/SOCS3 signaling pathway.Journal of translational medicine · 2023Article
- Maresin1 ameliorates MSU crystal-induced inflammation by upregulating Prdx5 expression.Molecular medicine (Cambridge, Mass.) · 2023Article
- Emerging Urate-Lowering Drugs and Pharmacologic Treatment Strategies for Gout: A Narrative Review.Drugs · 2023Review
- Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis.Frontiers in pharmacology · 2023Article
- Article
- Inflammatory Response to Regulated Cell Death in Gout and Its Functional Implications.Frontiers in immunology · 2022Review
- Dynamin-Related Protein 1 Is Involved in Mitochondrial Damage, Defective Mitophagy, and NLRP3 Inflammasome Activation Induced by MSU Crystals.Oxidative medicine and cellular longevity · 2022Article
- Active Flavonoids FromFrontiers in pharmacology · 2021Article
- Targeting Tristetraprolin Expression or Functional Activity Regulates Inflammatory Response Induced by MSU Crystals.Frontiers in immunology · 2021Article
- Function of Uric Acid Transporters and Their Inhibitors in Hyperuricaemia.Frontiers in pharmacology · 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundArhalofenate acid, the active acid form of arhalofenate, is a non-agonist peroxisome proliferator-activated receptor γ (PPARγ) ligand, with uricosuric activity via URAT1 inhibition. Phase II studies revealed decreased acute arthritis flares in arhalofenate-treated gout compared with allopurinol alone. Hence, we investigated the anti-inflammatory effects and mechanisms of arhalofenate and its active acid form for responses to monosodium urate (MSU) crystals.
methodsWe assessed in-vivo responses to MSU crystals in murine subcutaneous air pouches and in-vitro responses in murine bone marrow-derived macrophages (BMDMs) by enzyme-linked immunosorbent assay (ELISA), SDS-PAGE/Western blot, immunostaining, and transmission electron microscopy analyses.
resultsOral administration of arhalofenate (250 mg/kg) blunted total leukocyte ingress, neutrophil influx, and air pouch fluid interleukin (IL)-1β, IL-6, and CXCL1 in response to MSU crystal injection (p < 0.05 for each). Arhalofenate acid (100 μM) attenuated MSU crystal-induced IL-1β production in BMDMs via inhibition of NLRP3 inflammasome activation. In addition, arhalofenate acid dose-dependently increased activation (as assessed by phosphorylation) of AMP-activated protein kinase (AMPK). Studying AMPKα1 knockout mice, we elucidated that AMPK mediated the anti-inflammatory effects of arhalofenate acid. Moreover, arhalofenate acid attenuated the capacity of MSU crystals to suppress AMPK activity, regulated expression of multiple downstream AMPK targets that modulate mitochondrial function and oxidative stress, preserved intact mitochondrial cristae and volume density, and promoted anti-inflammatory autophagy flux in BMDMs.
conclusionsArhalofenate acid is anti-inflammatory and acts via AMPK activation and its downstream signaling in macrophages. These effects likely contribute to a reduction of gout flares.
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.