Component

Diclofenac

Context-specific entity; species, compartment and exposure are stated on each claim.

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Diclofenac inhibited steviol glucuronidation in human liver microsomes, with reported Ki 4.2 micromolar.

    Diclofenac → Human microsomal steviol glucuronidation source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    In vitro human liver microsomes.
    limitations
    Clinical relevance at ordinary sweetener exposure was not established; steviol is the possible interaction victim.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    A drug can interfere with the clearance step for a plant-derived metabolite.
    primary_references
    Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24296138/ · DOI 10.1016/j.fct.2013.11.028

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 66–72

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro human liver microsomes. · source_derived_draft · unverified_draft

    ## stevia-diclofenac-conjugation A drug can interfere with the clearance step for a plant-derived metabolite. Diclofenac inhibited steviol glucuronidation in human liver microsomes, with reported Ki 4.2 micromolar. Model: In vitro human liver microsomes. Limitations: Clinical relevance at ordinary sweetener exposure was not established; steviol is the possible interaction victim. Evidence access: Primary abstract Steviol glucuronidation and its potential interaction with UDP-glucuronosyltransferase 2B7 substrates. · 2014 · https://pubmed.ncbi.nlm.nih.gov/24296138/ · DOI 10.1016/j.fct.2013.11.028
    Complete structured claim and evidence

  2. Diclofenac inhibited OAT3-mediated steviol-glucuronide uptake, with IC50 8.0 micromolar.

    Diclofenac → Human OAT3-mediated steviol-glucuronide uptake source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    In vitro uptake assay; distinct from the glucuronidation experiment.
    limitations
    Combining the two records does not quantify a net in vivo interaction.
    nutrient_topic
    Stevia collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · Stevia
    plain_language
    The same drug intersects two different clearance steps.
    primary_references
    Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26525112/ · DOI 10.1016/j.fct.2015.10.011

    Stevia: glycoside metabolism, taste, ion channels and cross-nutrient mechanisms (2026-09-19) · lines 138–144

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · In vitro uptake assay; distinct from the glucuronidation experiment. · source_derived_draft · unverified_draft

    ## stevia-diclofenac-oat3 The same drug intersects two different clearance steps. Diclofenac inhibited OAT3-mediated steviol-glucuronide uptake, with IC50 8.0 micromolar. Model: In vitro uptake assay; distinct from the glucuronidation experiment. Limitations: Combining the two records does not quantify a net in vivo interaction. Evidence access: Primary abstract Transmembrane transport of steviol glucuronide and its potential interaction with selected drugs and natural compounds. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26525112/ · DOI 10.1016/j.fct.2015.10.011
    Complete structured claim and evidence

  3. The production of 15-HETE by aspirin-modified cyclooxygenase-2 was sensitive to inhibition by most non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors and the inhibition by indomethacin was time-dependent, but two potent structurally related drugs, diclofenac and meclofenamic acid, did not inhibit either the acetylated enzyme or the S516M mutant, so Ser516 plays an important role in the interaction with fenamate inhibitors.

    Diclofenac → 15(R)-hydroxyeicosatetraenoic acid source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/9016346.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2cc2efefceabbee7bb4f1052db8fc86ee218409fe56981cf92b707c7b0ef531b", "start_char": 0, "end_char": 1899, "text_sha256": "2cc2efefceabbee7bb4f1052db8fc86ee218409fe56981cf92b707c7b0ef531b"}
    experimental_model
    Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs
    exposure
    Aspirin acetylation and the methionine mutant, tested with indomethacin, diclofenac, meclofenamic acid and selective inhibitors
    limitations
    Quantifies how efficient the new activity is, which most descriptions of the switch do not. Purified and recombinant enzyme rather than intact cells.
    nutrient_topic
    Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid
    organism
    Enzyme
    plain_language
    Two common anti-inflammatories cannot touch the rerouted enzyme, because they needed the serine aspirin has taken.
    primary_references
    [asa-p9016346] Altered sensitivity of aspirin-acetylated prostaglandin G/H synthase-2 to inhibition by nonsteroidal anti-inflammatory drugs. (1997). https://pubmed.ncbi.nlm.nih.gov/9016346/ DOI: 10.1124/mol.51.1.52
    tissue_or_cell_type
    Cyclooxygenase-2

    Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 273–284

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs · source_derived_draft · unverified_draft

    ### asa-fenamates-do-not-block-it The production of 15-HETE by aspirin-modified cyclooxygenase-2 was sensitive to inhibition by most non-steroidal anti-inflammatory drugs including selective cyclooxygenase-2 inhibitors and the inhibition by indomethacin was time-dependent, but two potent structurally related drugs, diclofenac and meclofenamic acid, did not inhibit either the acetylated enzyme or the S516M mutant, so Ser516 plays an important role in the interaction with fenamate inhibitors. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Two common anti-inflammatories cannot touch the rerouted enzyme, because they needed the serine aspirin has taken. organism: Enzyme tissue_or_cell_type: Cyclooxygenase-2 experimental_model: Kinetic characterisation of aspirin-acetylated cyclooxygenase-2 and the S516M mutant against a panel of non-steroidal anti-inflammatory drugs limitations: Quantifies how efficient the new activity is, which most descriptions of the switch do not. Purified and recombinant enzyme rather than intact cells. exposure: Aspirin acetylation and the methionine mutant, tested with indomethacin, diclofenac, meclofenamic acid and selective inhibitors evidence_span: {"source_cache": "artifacts/aspirin-research/9016346.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2cc2efefceabbee7bb4f1052db8fc86ee218409fe56981cf92b707c7b0ef531b", "start_char": 0, "end_char": 1899, "text_sha256": "2cc2efefceabbee7bb4f1052db8fc86ee218409fe56981cf92b707c7b0ef531b"} [asa-p9016346] Altered sensitivity of aspirin-acetylated prostaglandin G/H synthase-2 to inhibition by nonsteroidal anti-inflammatory drugs. (1997). https://pubmed.ncbi.nlm.nih.gov/9016346/ DOI: 10.1124/mol.51.1.52
    Complete structured claim and evidence

What acts on it

  1. Diclofenac inhibition was unaffected by mutation of Arg-120 to alanine but was dramatically attenuated by the S530A mutation, and the crystal structure of diclofenac with murine COX-2 shows it bound in an inverted conformation with its carboxylate hydrogen-bonded to Tyr-385 and Ser-530, the first experimental demonstration that an acidic non-steroidal anti-inflammatory drug can bind in an orientation that precludes a salt bridge with Arg-120; Ser-530 is also important in time-dependent inhibition by nimesulide and piroxicam.

    Serine 530 of cyclooxygenase-1 → Diclofenac source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/12925531.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "732e941e7f912ae2495715634eabdef176dae39e32359609f15b05a230d5f6e0", "start_char": 0, "end_char": 1473, "text_sha256": "732e941e7f912ae2495715634eabdef176dae39e32359609f15b05a230d5f6e0"}
    experimental_model
    Site-directed mutants of COX-2 at Arg-120, Tyr-355, Tyr-348 and Ser-530 tested against a series of inhibitors, with a diclofenac co-crystal structure
    exposure
    Diclofenac, nimesulide and piroxicam against the mutant panel
    limitations
    Shows the acetylation serine is also a general binding determinant for other drugs. The structural work is on murine rather than human enzyme.
    nutrient_topic
    Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid
    organism
    Mouse enzyme
    plain_language
    The same serine aspirin attacks is where several other anti-inflammatories anchor themselves.
    primary_references
    [asa-p12925531] A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. (2003). https://pubmed.ncbi.nlm.nih.gov/12925531/ DOI: 10.1074/jbc.m305481200
    tissue_or_cell_type
    Cyclooxygenase-2

    Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 169–180

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Site-directed mutants of COX-2 at Arg-120, Tyr-355, Tyr-348 and Ser-530 tested against a series of inhibitors, with a diclofenac co-crystal structure · source_derived_draft · unverified_draft

    ### asa-ser530-binds-other-drugs Diclofenac inhibition was unaffected by mutation of Arg-120 to alanine but was dramatically attenuated by the S530A mutation, and the crystal structure of diclofenac with murine COX-2 shows it bound in an inverted conformation with its carboxylate hydrogen-bonded to Tyr-385 and Ser-530, the first experimental demonstration that an acidic non-steroidal anti-inflammatory drug can bind in an orientation that precludes a salt bridge with Arg-120; Ser-530 is also important in time-dependent inhibition by nimesulide and piroxicam. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: The same serine aspirin attacks is where several other anti-inflammatories anchor themselves. organism: Mouse enzyme tissue_or_cell_type: Cyclooxygenase-2 experimental_model: Site-directed mutants of COX-2 at Arg-120, Tyr-355, Tyr-348 and Ser-530 tested against a series of inhibitors, with a diclofenac co-crystal structure limitations: Shows the acetylation serine is also a general binding determinant for other drugs. The structural work is on murine rather than human enzyme. exposure: Diclofenac, nimesulide and piroxicam against the mutant panel evidence_span: {"source_cache": "artifacts/aspirin-research/12925531.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "732e941e7f912ae2495715634eabdef176dae39e32359609f15b05a230d5f6e0", "start_char": 0, "end_char": 1473, "text_sha256": "732e941e7f912ae2495715634eabdef176dae39e32359609f15b05a230d5f6e0"} [asa-p12925531] A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. (2003). https://pubmed.ncbi.nlm.nih.gov/12925531/ DOI: 10.1074/jbc.m305481200
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Aspirin maximally acetylates one monomer of human cyclooxygenase-2, the acetylated monomer forming 15-hydroperoxyeicosatetraenoic acid from arachidonic acid while the nonacetylated partner monomer forms mainly prostaglandin H2 but at only 15 to 20% of the rate of native enzyme, conclusions based on diclofenac binding a single monomer of native enzyme having an unmodified Ser530 and on diclofenac inhibiting prostaglandin H2 but not 15-hydroperoxyeicosatetraenoic acid formation by the acetylated enzyme.

    Aspirin / acetylsalicylic acid → The cyclooxygenase-2 homodimer source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/aspirin-research/20194532.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf", "start_char": 0, "end_char": 1441, "text_sha256": "09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf"}
    experimental_model
    Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them
    exposure
    Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates
    limitations
    Measures rates rather than presence, and reaches a much less generous estimate of resolvin formation than the reports it tests. It is an in vitro enzyme study, so it does not exclude accumulation or amplification in a living tissue.
    nutrient_topic
    Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. · Aspirin / acetylsalicylic acid
    organism
    Human enzyme
    plain_language
    Aspirin only ever modifies half of the paired enzyme, and the untouched half carries on at a fifth speed.
    primary_references
    [asa-p20194532] Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. (2010). https://pubmed.ncbi.nlm.nih.gov/20194532/ DOI: 10.1124/mol.109.063115
    tissue_or_cell_type
    Cyclooxygenase-2 homodimer

    Aspirin: the serine it acetylates, the enzyme that acetylation creates, the dose that separates platelet from vessel wall, and the metabolite that is a different drug (2026-09-22) · lines 325–336

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them · source_derived_draft · unverified_draft

    ### asa-only-one-monomer-is-acetylated Aspirin maximally acetylates one monomer of human cyclooxygenase-2, the acetylated monomer forming 15-hydroperoxyeicosatetraenoic acid from arachidonic acid while the nonacetylated partner monomer forms mainly prostaglandin H2 but at only 15 to 20% of the rate of native enzyme, conclusions based on diclofenac binding a single monomer of native enzyme having an unmodified Ser530 and on diclofenac inhibiting prostaglandin H2 but not 15-hydroperoxyeicosatetraenoic acid formation by the acetylated enzyme. Condition category: normal nutrient_topic: Aspirin research collection; topical membership is not evidence of a direct clinical effect, and aspirin is recorded separately from salicylate, the metabolite it becomes. plain_language: Aspirin only ever modifies half of the paired enzyme, and the untouched half carries on at a fifth speed. organism: Human enzyme tissue_or_cell_type: Cyclooxygenase-2 homodimer experimental_model: Quantitative characterisation of aspirin-acetylated human cyclooxygenase-2 monomers using diclofenac to distinguish them limitations: Measures rates rather than presence, and reaches a much less generous estimate of resolvin formation than the reports it tests. It is an in vitro enzyme study, so it does not exclude accumulation or amplification in a living tissue. exposure: Aspirin acetylation with arachidonic, eicosapentaenoic and docosahexaenoic acid as substrates evidence_span: {"source_cache": "artifacts/aspirin-research/20194532.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf", "start_char": 0, "end_char": 1441, "text_sha256": "09427e18078449741ea9ea42dc91a16f50ca9f604ec05c4decbb255731104eaf"} [asa-p20194532] Asymmetric acetylation of the cyclooxygenase-2 homodimer by aspirin and its effects on the oxygenation of arachidonic, eicosapentaenoic, and docosahexaenoic acids. (2010). https://pubmed.ncbi.nlm.nih.gov/20194532/ DOI: 10.1124/mol.109.063115
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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