Mitraphylline

Mitraphylline at a Glance

Mitraphylline is the marker pentacyclic oxindole alkaloid of cat’s claw (Uncaria tomentosa).

That chemotype distinction matters commercially: Uncaria tomentosa occurs as pentacyclic and tetracyclic oxindole chemotypes, the two are held to be pharmacologically opposed, and mitraphylline identifies the pentacyclic one — which is the type used for immune and inflammatory indications.

Its preclinical anti-inflammatory and cytokine-modulating activity is the mechanistic rationale for cat’s claw’s use in arthritis.

What It's Used For

Mitraphylline is the marker pentacyclic oxindole alkaloid (POA) of cat’s claw (Uncaria tomentosa) — chemically distinct from the Uncaria indole alkaloids such as its co-alkaloid hirsutine. Its own literature is a coherent but entirely preclinical anti-inflammatory/immunomodulatory story — the mechanistic rationale behind cat’s claw’s one genuinely human-anchored use (rheumatoid/osteoarthritis) — plus micromolar cytotoxicity against tumor lines. The load-bearing honesty point: cat’s claw’s clinical trials used the whole/purified extract, not isolated mitraphylline, so the clinical benefit cannot be attributed to this molecule. (One accuracy note: the popular “good POA / bad TOA alkaloid” marketing framing is not supported by the primary literature — both classes occur in both chemotypes.)

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. No human isolate data, so scores stay low by design.

01Anti-inflammatory / immunomodulatoryShaky32%In-vivo murine + primary human-cell cytokine studies ^{1,2,3Reference 1Rojas-Durán R et al. · 2012Anti-inflammatory activity of mitraphylline isolated from Uncaria tomentosa barkView study →Reference 2Montserrat-de la Paz S et al. · 2015Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human monocytes: skew toward M2 macrophagesView study →Reference 3Montserrat-de la Paz S et al. · 2016Mitraphylline inhibits lipopolysaccharide-mediated activation of primary human neutrophilsView study →}

02Anticancer / cytotoxicShaky20%Micromolar cytotoxicity across tumor lines ^{4,5,6Reference 4García Giménez D et al. · 2010Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline from Uncaria tomentosa bark on human Ewing’s sarcoma and breast cancer cell linesView study →Reference 5García Prado E et al. · 2007Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa, on human glioma and neuroblastoma cell linesView study →Reference 6Bacher N et al. · 2006Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cellsView study →}

03NeuroprotectiveShaky10%One in-vitro amyloid-β study ^{7Reference 7Tan MA · 2020Neuroprotective potential of the oxindole alkaloids isomitraphylline and mitraphylline in human neuroblastoma SH-SY5Y cellsView study →}

Mechanisms

NF-κB is the widely-cited upstream node for cat’s claw’s cytokine effects, but the isolated-mitraphylline studies demonstrate the downstream cytokine outputs rather than assaying NF-κB directly — stated honestly, not over-claimed.

Pharmacokinetics

Mitraphylline’s pharmacokinetics are poorly characterized, with no isolated-compound human data (Cmax, half-life, bioavailability). It is a low-abundance oxindole alkaloid — total oxindole alkaloids in cat’s claw bark are on the order of tenths of a percent and vary widely by chemotype, part and season ^{9Reference 9Heitzman ME et al. · 2005Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae)View study →} — so isolate exposure from crude preparations is small. Oral 30 mg/kg was pharmacologically active in mice ^{1Reference 1Rojas-Durán R et al. · 2012Anti-inflammatory activity of mitraphylline isolated from Uncaria tomentosa barkView study →}, implying some oral absorption, but there is no formal ADME. A 2024 study found U. tomentosa extract and its major constituents (including mitraphylline) modulate multispecific drug transporters, flagging herb–drug-interaction potential ^{8Reference 8Szilvásy N et al. · 2024Modulation of multispecific transporters by Uncaria tomentosa extract and its major phytoconstituentsView study →} — though the frequently-cited CYP3A4/protease-inhibitor interaction is a whole-extract finding, not demonstrated for isolated mitraphylline.

Clinical trials

There are no trials of isolated mitraphylline. Human cat’s claw trials (rheumatoid arthritis, knee osteoarthritis, breast-cancer chemo-adjuvant) all used whole/purified/freeze-dried extract and cannot be attributed to this single alkaloid.

Last checked: July 2026.

Toxicity & Safety

Mitraphylline looks benign on the preclinical data — it spared normal cells at concentrations that killed tumor lines — but there is no human safety data at all, and the practical concern is a theoretical herb–drug interaction rather than the molecule’s own toxicity.

Safety at a Glance

✅ Low / no toxicityDrug interactions

• Comparatively selective. No cytotoxicity against normal murine macrophages up to 100 µM, well above the concentrations that affect tumor lines.
• Not kratom’s mitragynine. A chemically distinct molecule; kratom’s opioid pharmacology does not apply here.
• Avoid in pregnancy and lactation. Cat’s claw is traditionally cautioned in pregnancy.
• Theoretical herb–drug interaction. Transporter and CYP modulation has been shown at the whole-extract level.
• No human safety data. No genotoxicity or organ-toxicity studies exist for the isolate.

Full Safety & Interactions Detail

Mitraphylline has a low toxicity verdict on the available preclinical data — it showed no cytotoxicity against normal murine peritoneal macrophages up to 100 µM, so its tumor-line cytotoxicity (IC50 ~12–17 µM) is comparatively selective ^{1,4Reference 1Rojas-Durán R et al. · 2012Anti-inflammatory activity of mitraphylline isolated from Uncaria tomentosa barkView study →Reference 4García Giménez D et al. · 2010Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline from Uncaria tomentosa bark on human Ewing’s sarcoma and breast cancer cell linesView study →}.

There are no genotoxicity, organ-toxicity or human safety data for the isolate, and the main practical concern is a theoretical herb–drug interaction via transporter/CYP modulation at the extract level ^{8Reference 8Szilvásy N et al. · 2024Modulation of multispecific transporters by Uncaria tomentosa extract and its major phytoconstituentsView study →}.

This is a chemically distinct molecule from kratom’s mitragynine, and kratom’s opioid pharmacology must not be attributed to it.

Dosage

There is no established dose for isolated mitraphylline — it is not used as a standalone supplement but functions as the standardization marker for cat’s claw pentacyclic-chemotype extracts (products are standardized to POA content), not as a dosed ingredient, so no human dosing guidance exists.

References

1. Rojas-Durán R, et al. (2012). Anti-inflammatory activity of mitraphylline isolated from Uncaria tomentosa bark. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/22846434/
2. Montserrat-de la Paz S, et al. (2015). Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human monocytes: skew toward M2 macrophages. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/25975515/
3. Montserrat-de la Paz S, Fernandez-Arche A, de la Puerta R, et al. (2016). Mitraphylline inhibits lipopolysaccharide-mediated activation of primary human neutrophils. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/26926175/
4. García Giménez D, et al. (2010). Cytotoxic effect of the pentacyclic oxindole alkaloid mitraphylline from Uncaria tomentosa bark on human Ewing’s sarcoma and breast cancer cell lines. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/19724995/
5. García Prado E, et al. (2007). Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa, on human glioma and neuroblastoma cell lines. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/17296291/
6. Bacher N, et al. (2006). Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells. British Journal of Haematology. https://pubmed.ncbi.nlm.nih.gov/16445836/
7. Tan MA, An SSA (2020). Neuroprotective potential of the oxindole alkaloids isomitraphylline and mitraphylline in human neuroblastoma SH-SY5Y cells. 3 Biotech. https://pubmed.ncbi.nlm.nih.gov/33194521/
8. Szilvásy N, Lajer P, Horváth A, et al. (2024). Modulation of multispecific transporters by Uncaria tomentosa extract and its major phytoconstituents. Pharmaceutics. https://pubmed.ncbi.nlm.nih.gov/39598486/
9. Heitzman ME, et al. (2005). Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae). Phytochemistry. https://pubmed.ncbi.nlm.nih.gov/15649507/

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