Cat's Claw (Uncaria tomentosa): A Comprehensive Reference
1. Identity and Botanical Classification
Nomenclature and Taxonomy
Cat's claw (Uncaria tomentosa (Willd. ex Schult.) DC., Family: Rubiaceae) is a tropical medicinal vine originating in the Amazon rainforest and other areas of South and Central America. It is commonly known as cat's claw, a name derived from the Spanish word uña de gato, which identifies the small, curved-back thorns on the stem at the leaf junction. Additional vernacular names include "the life-giving vine of Peru," "saventaro," and "uña de gato."
Cat's claw is a woody vine that grows wild in the Amazon rainforest and other tropical areas of Central and South America. The two most common species are U. tomentosa and U. guianensis. Most commercial preparations of cat's claw in the United States contain U. tomentosa. Note that Uncaria tomentosa is not the same as Uncaria rhynchophylla (twig and thorn; Uncaria sinensis; Ramulus) or Uncaria guianensis; they are three different species.
Morphology and Geography
Cat's claw is a scrambling liana up to 20–30 meters long, with a main stem up to 25 cm in diameter. It grows as high as altitudes of 500–600 meters above sea level, in high forests with abundant insolation, reaching 18–19 m in height. It is widely distributed in Bolivia, Brazil, Colombia, Costa Rica, Ecuador, Guatemala, French Guiana, Guyana, Nicaragua, Panama, Peru, and Venezuela.
Plant Parts Used and Common Preparations
The parts primarily utilized for medicinal purposes are the inner bark and root. Several formulations of cat's claw, including tinctures, decoctions, capsules, extracts, and teas, are available in the market. A decoction of U. tomentosa bark, root, and leaves is used traditionally for different health problems.
2. Traditional and Historical Use
Indigenous Amazonian Traditions
Cat's claw is a Rubiaceae used for at least 2,000 years among some Peruvian tribes, especially the Asháninka. U. tomentosa has been used in Peru for over 2,000 years, but it was first introduced to Europe in the 1990s as a supplemental medicine for AIDS and cancer.
Peruvian tribes — with the longest recorded history of use being the Asháninka Indians — have used cat's claw as an anti-inflammatory agent, contraceptive, and emmenagogue; for cancer, gastric ulcer, diarrhoea, asthma, wounds, gonorrhoea, arthritis, rheumatism, acne, diabetes, diseases of the urinary tract, and menstrual irregularity; to recover from childbirth; and as a tonic to ward off disease or as an abortifacient.
Uncaria tomentosa is widely used in Peruvian and Brazilian traditional medicine as an anti-inflammatory, antinociceptive, and antiasthmatic agent, and to prevent diseases. It is included in Brazil's National List of Essential Medicines (RENAME), provided by the Brazilian Ministry of Health to all municipalities through the National Health System (SUS).
Preparation Methods in Traditional Practice
Cat's claw has a long history within the indigenous tribes of the Amazon River basin, whereby the bark and roots were prepared as a decoction to treat various ailments. Sometimes cat's claw is used in combination with other local herbs, such as chuchuhuasi (Maytenus krukovii) bark, to treat arthritis.
Traditional Contraindications
It has been traditionally contraindicated in pregnancy, during lactation, and for children. A related species (Uncaria guianensis) has been used in South America for wound healing, as a sedative, and to treat intestinal ailments, but is not considered as strong as Uncaria tomentosa.
3. Key Phytochemical Constituents
Overview of Chemical Classes
Phytochemical studies have shown the presence of a wide range of bioactive compounds in various parts of U. tomentosa, including alkaloids of the indole and oxindole type; triterpenes based on ursolic, oleanolic, or quinovic acid; glycosides, sterols and phenolic compounds; phenolic acids; and flavan-3-ol–related compounds like proanthocyanidins.
Constituents of cat's claw extracts include oxindole alkaloids (isopteropodine, pteropodine, rhynchophylline, mitraphylline, speciophylline, uncarine F, uncarine E), indole alkaloidal glucosides (cadambine, 3-dihydrocadambine, and 3-isodihydrocadambine), quinovic acid glycosides, tannins, polyphenols, catechins, and beta-sitosterol.
Oxindole Alkaloids: The Principal Bioactive Compounds
U. tomentosa is rich in alkaloids, including tetracyclic indole, tetracyclic oxindole, pentacyclic indole, pentacyclic oxindole, and glycoindole alkaloids. These are widely regarded as the primary pharmacologically active constituents. Currently, the pentacyclic and tetracyclic oxindole alkaloids (POA and TOA) are being used as chemical markers in quality control of raw material and derivatives from U. tomentosa, but other studies indicate that other phytochemicals contribute to its biological activities.
Pentacyclic oxindole alkaloids (POAs) include mitraphylline, isomitraphylline, pteropodine, and isopteropodine. These are associated with immune-modulating effects. Mitraphylline, in particular, is a major POA known for its anti-inflammatory activity. Tetracyclic oxindole alkaloids (TOAs), including rhynchophylline and isorhynchophylline, may have different effects, potentially influencing the central nervous system and cardiovascular system, for example blood pressure reduction.
The Two Chemotypes
Uncaria tomentosa occurs in two chemotypes, each varying greatly in its alkaloid content. One predominantly contains pentacyclic oxindole alkaloids, while the other is rich in the tetracyclic oxindoles. The alkaloid composition of U. tomentosa changes significantly over time and between plant generations. The total alkaloid content has been reported to vary from 0.036 to 3.83% (w/w) of the dried root bark, depending on harvesting; and individual plants can switch from one alkaloid pattern to the other over time.
It has been stated that a mixture of the two chemotypes of cat's claw is unsuitable for therapeutic use unless certified to contain less than 0.02% tetracyclic oxindole alkaloids. The TOAs are believed to be POA antagonists with respect to the POAs' desirable effects, and therefore it is important to distinguish between the two chemotypes. More recent phytochemical work has identified a third chemotype: three chemotypes based on the oxindole alkaloid profile have been noticed in U. tomentosa, namely chemotype I (POA cis D/E ring junction), chemotype II (POA trans D/E ring junction), and chemotype III (TOA).
Other Notable Constituents
Different organic and aqueous extracts of Uncaria tomentosa contain biologically active substances including immunostimulating pentacyclic oxindole alkaloids, ursane-type pentacyclic triterpenes and quinovic acid glycosides (with reported anti-inflammatory properties and ability to inhibit viral replication), and carboxyl alkyl esters including quinic acid derivatives (reported to reduce proliferation of neoplastic cells and stimulate DNA repair), as well as antioxidants such as catechin monomers and proanthocyanidins.
Specific proanthocyanidins — namely epicatechin dimers and variants thereof — are polyphenolic components within Uncaria tomentosa that have been shown to possess both plaque- and tangle-reducing and inhibitory activity in preclinical Alzheimer's research, though this remains preliminary.
4. Mechanisms of Action
Anti-Inflammatory Mechanisms
The inhibition of the activation of nuclear factor-κB (NF-κB), which serves as an important regulator of host immune and anti-inflammatory responses, and TNF-α inhibition tests have demonstrated the ability of U. tomentosa extracts to suppress chronic inflammation. The latter is considered the primary mechanism of the anti-inflammatory and immunomodulatory actions of this species.
Cat's claw extract has been found effective in inhibiting lipopolysaccharide (LPS)-induced free radical production and subsequent lipid peroxidation in murine macrophage cell lines. TNF-α production and iNOS expression via NF-κB were also inhibited by the extract.
Immunomodulatory Mechanisms
Pentacyclic oxindole alkaloids present in the extracts are suggested as the bioactive compounds for immune modulation; these are known to modulate the cellular immune system by affecting T and B lymphocytes, influencing phagocytosis, and inhibiting the activation of lymphocyte proliferation.
In vitro research has shown that pentacyclic but not tetracyclic oxindole alkaloids from U. tomentosa induced endothelial cells to release factors that significantly enhanced the proliferation of normal human resting or weakly activated B and T lymphocytes, while inhibiting the proliferation of lymphoblasts. Tetracyclic oxindole alkaloids dose-dependently reduced the activity of pentacyclic oxindole alkaloids on human endothelial cells.
U. tomentosa extracts preserve CD4+ and CD8+ T cells and possibly stimulate cytokines that favor the polarization of CD4+ Th2 cells. These cells play an important role in autoimmune diseases such as rheumatoid arthritis by modulating the excessive activity of Th1 cells.
DNA Repair Enhancement
Repair of DNA single strand breaks (SSB) and double strand breaks (DSB) 3 hours after 12 Gy whole body irradiation of rats were significantly improved in C-MED-100 (an aqueous extract of U. tomentosa)–treated animals (P < 0.05).
Antiviral Mechanisms
The antiviral activity of quinovic acid glycosides has been demonstrated in vitro against vesicular stomatitis, RNA (a minus-strand RNA virus), and rhinovirus 1B. The in vitro antiherpetic activity of hydroethanolic U. tomentosa extract, as well as purified fractions of oxindole alkaloids and quinovic acid glycosides, against herpes simplex virus (HSV) infections and the protective activity of these preparations against UV-induced DNA damage have also been assessed.
5. Scientific Evidence by Area of Use
Overall Evidence Assessment
There have been very few high-quality clinical trials (studies done in people) of cat's claw. There is no conclusive scientific evidence based on studies in people that supports using cat's claw for any health purpose, including COVID-19. Some research has been done in people on the effect of cat's claw on various conditions, but many of the studies did not use rigorous methods and did not include enough study participants to allow definite conclusions to be reached.
Osteoarthritis
Among 45 patients with painful osteoarthritis of the knee treated with cat's claw (100 mg once daily) or placebo for 4 weeks, pain scores decreased more with cat's claw, but nighttime pain and swelling did not change. Cat's claw was well tolerated and there were no serious adverse events or changes in serum ALT and AST values during treatment. This trial used freeze-dried Uncaria guianensis.
A study was designed to determine if a natural mineral supplement (sierrasil), alone and in combination with a cat's claw extract (Uncaria guianensis, 100 mg/day), had therapeutic potential in mild to moderate osteoarthritis of the knee. Patients (n = 107) were randomly assigned to one of four groups in a double-blind study for 8 weeks. Primary efficacy variables were WOMAC scores, with VAS pain scores, rescue medication use, and tolerability as secondary variables. The combination group demonstrated earlier symptom relief compared to placebo.
In humans, the evidence for efficacy of cat's claw extracts has been mixed. A critical review concluded there is little evidence for its efficacy in treating arthritis or inflammatory conditions, and that, although generally well tolerated, it can cause drug–drug interactions, particularly with anticoagulants.
Rheumatoid Arthritis
In a published randomized, 52-week, 2-phase study evaluating safety and clinical efficacy of a pentacyclic chemotype extract of U. tomentosa in patients with active rheumatoid arthritis, 40 patients undergoing sulfasalazine or hydroxychloroquine treatment were enrolled. During the first 24-week double-blind phase, patients were treated with the extract or placebo. The second phase (28 weeks) had all patients receive the plant extract. Twenty-four weeks of treatment with the extract resulted in a reduction of the number of painful joints compared to placebo (53.2% vs. 24.1%; p = 0.044).
In this randomized trial of cat's claw (30 mg daily) vs. placebo in 40 patients with rheumatoid arthritis, adverse events were uncommon and minor, the most common being dyspepsia and pruritus; laboratory results did not change. The trial was small and the clinical significance of findings remains uncertain; replication in larger studies has not been performed.
An extract of U. tomentosa was superior to placebo in 50 patients with rheumatoid arthritis, decreasing the number of painful joints, morning stiffness, pain intensity, and joint edema (Mur et al., 2002).
DNA Repair and Immune Enhancement
In a human volunteer study, one group was supplemented with a 250 mg tablet containing an aqueous extract of U. tomentosa (C-Med-100), and another group with a 350 mg tablet, for 8 consecutive weeks. DNA repair after induction of DNA damage by hydrogen peroxide was measured three times before supplementation and three times in the final 3 weeks of the supplement period. There were no drug-related toxic responses. There was a statistically significant decrease in DNA damage and a concomitant increase in DNA repair in both supplement groups (250 and 350 mg/day) compared with non-supplemented controls (p < 0.05).
In a companion human volunteer study, C-MED-100 was given daily at 5 mg/kg for 6 consecutive weeks to four healthy adult males. No toxicity was observed and white blood cell counts were significantly elevated (P < 0.05) after supplementation. These trials were limited by very small sample sizes and must be considered preliminary.
Adjuvant Use in Cancer / Chemotherapy
A randomized clinical trial assessed the effectiveness of U. tomentosa in reducing the adverse effects of chemotherapy. Patients with invasive ductal carcinoma (Stage II) undergoing FAC chemotherapy (fluorouracil, doxorubicin, cyclophosphamide) were divided into two groups: one received chemotherapy plus 300 mg dry U. tomentosa extract per day, the other received chemotherapy alone as control. Blood samples were collected before each of the six chemotherapy cycles. Uncaria tomentosa reduced neutropenia caused by chemotherapy and was able to restore cellular DNA damage. The authors concluded that it is an effective adjuvant treatment for breast cancer. This finding warrants independent replication before conclusions can be drawn.
Antiviral Activity
U. tomentosa has demonstrated antiviral effects against SARS-CoV-2 in vitro, with a reduction in viral titer and cytopathic effect (CPE) after 48 hours of treatment on Vero E6 cells. The authors hypothesized that U. tomentosa stem bark could be promising in the development of new therapeutic strategies against SARS-CoV-2. No completed human clinical trials of cat's claw specifically for COVID-19 or most viral infections have been published.
Neurodegenerative Disease (Preclinical)
A specific plant extract (PTI-00703 cat's claw, Uncaria tomentosa from a specific Peruvian source) was identified in preclinical research as a potent inhibitor and reducer of both beta-amyloid fibrils (the main component of plaques) and tau protein paired helical filaments/fibrils (the main component of tangles). Specific proanthocyanidins — namely epicatechin dimers and variants thereof — are newly identified polyphenolic components within Uncaria tomentosa that possess both plaque- and tangle-reducing and inhibitory activity. This work is preclinical; no human clinical trials in Alzheimer's disease have been conducted.
6. Body Systems and Health Areas
- Musculoskeletal / Rheumatological: Cat's claw is used for its antiinflammatory and immune-modulating effects in the treatment of muscle and joint aches and the symptoms of chronic inflammatory conditions.
- Immune System: This plant has potent immunostimulant action, antioxidant, and anti-inflammatory activities.
- Gastrointestinal: U. tomentosa has traditional uses including gastritis, rheumatism, cirrhosis, gonorrhea, and cancers of the female genital tract.
- Cardiovascular: Antihypertensive activity is among the pharmacological properties reported for the plant.
- Oncology (adjuvant/supportive): Preclinical and clinical studies highlight the potential of Uncaria-derived compounds as a multifaceted approach to cancer treatment.
- DNA Repair / Cellular Integrity: In a human clinical study, Uncaria tomentosa treatment led to a decrease in DNA damage and an increase in DNA repair.
- Neurological (preclinical only): Proanthocyanidins from the plant show preclinical plaque- and tangle-reducing activity relevant to Alzheimer's disease models.
7. Dosage Forms and Reported Study Dosages
The typical recommended dose of U. tomentosa is one gram given two to three times daily. A standardized extract attributed to the specific chemotype of this species may consist of less than 0.5% oxindole alkaloids and 8% to 10% carboxy alkyl esters.
The following dosages have been specifically reported in published studies:
- In the osteoarthritis knee trial (Piscoya et al., 2001), patients received freeze-dried cat's claw at 100 mg once daily for 4 weeks.
- In the rheumatoid arthritis trial (Mur et al., 2002), patients received 30 mg of a standardized extract daily.
- In the sierrasil/cat's claw combination osteoarthritis RCT (Miller et al., 2005), patients received low-dose sierrasil (2 g/day) plus cat's claw extract (100 mg/day) for 8 weeks.
- In the breast cancer adjuvant trial, patients received 300 mg dry U. tomentosa extract per day concurrently with FAC chemotherapy.
- In the DNA repair human volunteer trial (Sheng et al., 2001), subjects received either 250 mg or 350 mg daily of the aqueous extract C-Med-100 for 8 consecutive weeks.
- In the C-MED-100 immune study, C-MED-100 was given daily at 5 mg/kg for 6 consecutive weeks to healthy adult males.
Several formulations of cat's claw are available in the market, including tinctures, decoctions, capsules, extracts, and teas. The specific chemical makeup, particularly the alkaloid profile, can vary depending on the plant's chemotype, geographical source, harvest time, and preparation methods.
8. Safety, Adverse Effects, and Drug Interactions
General Safety Profile
Cat's claw appears to be safe when used orally for short periods of time, as much as 6 months. Cat's claw has not been implicated in causing liver injury according to the NIH LiverTox database. Although rats were treated daily with U. tomentosa extracts at doses of 10–80 mg/kg for 8 weeks or 160 mg/kg for 4 weeks, no acute or chronic toxicity signs were observed symptomatically.
Adverse Effects Reported in Clinical Trials
In the rheumatoid arthritis randomized trial, adverse events were uncommon and minor, with the most common being dyspepsia and pruritus; laboratory results did not change. At higher doses, cat's claw can lead to constipation, increased uric acid levels, and cardiovascular problems.
A case was reported of a 59-year-old woman with mantle-cell lymphoma who had raised liver enzymes; self-medication with cat's claw was deemed the most likely cause. Cat's claw was withdrawn and her liver tests normalized within 60 days. This is an isolated case report, and cat's claw has not been implicated in causing liver injury more broadly.
Pregnancy and Lactation
Cat's claw has been traditionally contraindicated in pregnancy, during lactation, and for children. Cat's claw contains alkaloids that have been shown to have antiproliferative effects in breast cancer cells and leukemic and lymphoma cell lines through induction of apoptosis. While there are no definitive data, it is plausible that the contraceptive effects of cat's claw are related to its antiproliferative effects and induction of apoptosis — thus, the fetus may be at risk due to failure of cellular replication and/or differentiation.
Drug Interactions
There are theoretical reasons to suspect that cat's claw might interact with anticoagulant, antiplatelet, and blood pressure drugs, and other supplements as well.
Cat's claw might decrease how quickly the liver breaks down some medications, meaning taking cat's claw along with some medications metabolized by the liver can increase their effects and side effects. In vitro studies have specifically examined CYP enzyme inhibition: CYP3A4 was inhibited approximately 40% at a Samento (cat's claw) concentration of 1%. Samento significantly induced mRNA expression of CYP2J2, UGT1A3, UGT1A9, ABCB1, and SLCO1B1 and strongly activated the pregnane X receptor (PXR). Clinical studies are strongly recommended to clarify whether the effects observed in vitro are of clinical significance.
U. tomentosa extract significantly inhibited all ABC transporters and the majority of the SLC transporters tested in vitro. Of the investigated oxindole alkaloids, isopteropodine significantly inhibited OATP, OCT1 and OCT2, OAT3, ENT4, MDR1, and BCRP transporters.
Certain individuals should use cat's claw with caution: its immune-stimulating potential may counteract the effects of immunosuppressant drugs, such as cyclosporine and corticosteroids.
Renal Safety
The use of this plant has been associated in individual cases with development of acute interstitial nephritis leading to acute renal failure. This is based on isolated case reports, not systematic data, and should be noted as a theoretical concern.
Chemotype and Standardization Considerations
Discrepancies between studies reinforce the importance of standardizing U. tomentosa extracts, since diverse chemotypes might present differential pharmacological activities. The determination of the chemotype is crucially important in the plant's analysis and processing, for the purpose of obtaining a pharmaceutical preparation.
References
- National Center for Complementary and Integrative Health (NCCIH): Cat's Claw: Usefulness and Safety
- NIH LiverTox (NCBI Bookshelf): Cat's Claw
- European Medicines Agency (EMA): Draft Assessment Report on Uncaria tomentosa (Willd. ex Schult.) DC., cortex
- Yepes-Pérez et al. (2020). Uncaria tomentosa (Willd. ex Schult.) DC.: A Review on Chemical Constituents and Biological Activities. Applied Sciences, 10(8), 2668. MDPI.
- Uncaria tomentosa as a Promising Natural Source of Molecules with Multiple Activities: Review of Its Ethnomedicinal Uses, Phytochemistry and Pharmacology. PMC / NCBI.
- Frontiers in Pharmacology (2024): Anti-inflammatory and/or immunomodulatory activities of Uncaria tomentosa (cat's claw) extracts: A systematic review and meta-analysis of in vivo studies.
- Mur E, Hartig F, Eibl G, Schirmer M. Randomized double blind trial of an extract from the pentacyclic alkaloid-chemotype of Uncaria tomentosa for the treatment of rheumatoid arthritis. J Rheumatol. 2002;29(4):678–81. PubMed.
- Sheng Y, Li L, Holmgren K, Pero RW. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study. Phytomedicine. 2001;8(4):275–82. PubMed.
- Sheng Y, Bryngelsson C, Pero RW. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa. J Ethnopharmacol. 2000;69(2):115–26. PubMed.
- Uncaria tomentosa — Adjuvant Treatment for Breast Cancer: Clinical Trial. PMC / NCBI.
- Snow AD et al. The Amazon rain forest plant Uncaria tomentosa (cat's claw) and its specific proanthocyanidin constituents are potent inhibitors and reducers of both brain plaques and tangles. Scientific Reports. 2019. PMC.
- Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer and Normal Cells, and Effects Cisplatin Cytotoxicity. PMC / NCBI.
- Biological Basis for the Use of Botanicals in Osteoarthritis and Rheumatoid Arthritis: A Review. PMC / NCBI.
- Modulation of Multispecific Transporters by Uncaria tomentosa Extract and Its Major Phytoconstituents. PMC / NCBI.
- Weiss J. Herb–Drug Interaction Potential of Anti-Borreliae Effective Extracts from Uncaria tomentosa (Samento) and Otoba parvifolia (Banderol) Assessed In Vitro. Molecules. 2018. PMC.
- Wurm M et al. Pentacyclic oxindole alkaloids from Uncaria tomentosa induce human endothelial cells to release a lymphocyte-proliferation-regulating factor. PubMed.
- Uncaria tomentosa: Overview. ScienceDirect Topics.
- EBM Consult: Why Cat's Claw (Uncaria tomentosa) Should Be Avoided During Pregnancy.