Cat's Claw

Scientific Name(s): Uncaria tomentosa (Willd.) DC and Uncaria guianensis (Aubl.) Gmel. Family: Rubiaceae

Common Name(s): Cat's claw , Cortex Uncariae , life-giving vine of Peru , samento , uña de gato , various commercial preparations, including C-Med 100 and Reparagen

Uses

Despite multiple purported effects, controlled clinical trials are lacking. Suggested anti-inflammatory, anticancer, and immunostimulant properties are largely based on in vitro and limited animal studies.

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Dosing

One gram of root bark given 2 to 3 times daily is a typical dose, while 20 to 30 mg of a root bark extract has been recommended. Clinical trials are generally lacking to support appropriate dosages. A standardized extract containing 8% to 10% carboxy alkyl esters and less than 0.5% oxindole alkaloids has been used in clinical studies in doses of 250 to 300 mg.

Contraindications

Cat's claw products should be avoided before and after surgery, as well as by those using immunosuppressant therapy and in children due to lack of safety data.

Pregnancy/Lactation

Information regarding safety and efficacy during pregnancy and lactation is lacking.

Interactions

Case reports are generally lacking; however, there is a reported interaction with protease inhibitors.

Adverse Reactions

Although reports of adverse effects are rare, GI complaints (nausea, diarrhea, stomach discomfort), renal effects, neuropathy, and an increased risk of bleeding with anticoagulant therapy are possible.

Toxicology

Historical ethnomedicinal evidence and current use by consumers suggest low toxicity; however, toxicological studies are limited.

Botany

Cat's claw is a tropical vine of the madder family (Rubiaceae). The name describes the small, curved-back spines on the stem at the leaf juncture. The genus Uncaria is found mainly in tropical regions of Southeast Asia, the Asian continent, and South America. There are 34 reported species of Uncaria .

U. tomentosa and U. guianensis species are found in South America and are lianas, or high-climbing, twining, woody vines growing up to 305 m in length and several centimeters in diameter. Both species are known in Peru as uña de gato (Spanish for cat's claw). Large amounts of U. guianensis are collected in South America for the European market, while American sources prefer U. tomentosa . By 1997, over 50 dietary supplement manufacturers offered cat's claw products in the United States.

One Asian species, known as gambir or pole catechu ( Uncaria gambir [Hunter] Roxb.), is a widely used tanning agent that also has had a long history of medicinal use as an astringent and antidiarrheal. The related species Uncaria rhynchophylla is more commonly used in China. 1 , 2 , 3

History

Cat's claw has had a history of folkloric use in South America for wound healing and for treating arthritis, gastric ulcers, intestinal disorders, and some skin disorders and tumors. The part used medicinally is the inner bark of the vine or root. In Peru, a boiled decoction of U. guianensis is used as an anti-inflammatory, antirheumatic, and contraceptive agent, as well as for treating gastric ulcers and tumors, gonorrhea (by the Bora tribe), dysentery (by the Indian populations of Colombia and Guiana), and cancers of the urinary tract in women. The Ashanica Indians believe that samento ( U. tomentosa ) has life-giving properties and ingest a cup of the decoction every 1 to 2 weeks to ward off disease, treat bone pain, and cleanse the kidneys. Other reported uses include treatment for abscesses, asthma, chemotherapy adverse effects, fever, hemorrhage, rheumatism, skin impurities, urinary tract inflammation, weakness, and wounds, as well as for disease prevention and recovery from childbirth.

Demand for the bark has been partially attributed to European reports of its clinical use with zidovudine in AIDS treatment. The demand for the bark in the United States is based on its purported use as a tea in treating diverticulitis, hemorrhoids, peptic ulcers, colitis, gastritis, parasites, and “leaky gut syndrome.” There are, however, no controlled clinical trials to support these uses. 2 , 4 , 5

Chemistry

Many reports exist on the chemical composition of the various Uncaria species and differentiations of the compounds found in different plant parts; reviews have also been published. More than 150 chemical compounds have been isolated from the genus, with approximately 50 chemical entities attributed to U. tomentosa , some of which possibly novel to that species.

Two different chemotypes of U. tomentosa have been described, while U. guianensis and U. rhynchophylla have also been extensively studied. No official standardization exists, and commercially available preparations may consist of mixed plant sources despite claiming to be “100% pure.” Inter-batch variations have been reported.

Key compounds common to the genus are primarily the indole and oxindole alkaloids, pentacyclic triterpenoids, and flavonoids. Alkaloids found in most of the species include hirsuteine, hirsutine, mitraphylline, and rhychophylline. The terpenoids include cytotoxic phenolic acid esters, uncarric acids, and glycosides, while other novel compounds include quinovic acids, sterols, and coumarins. 3 , 6 , 7 , 8 , 9

Uses and Pharmacology

Anti-inflammatory

Cat's claw is a potent inhibitor of production of the pro-inflammatory cytokine tumor necrosis factor (TNF)-alpha in vitro. The anti-inflammatory activity appears to involve suppression of TNF-alpha synthesis, as well as the secretion of nitric oxide and interleukins. 10 , 11 , 12 , 13 The antioxidant activity associated with the phenolic and flavonoid content does not appear to be related to inhibition of nuclear factor kappaB (NF-kB) because quinic acid esters have no inherent antioxidant potential, but inhibit NF-kB. 11 , 14

Animal data

The pentacyclic oxindole alkaloids were possibly associated with the anti-inflammatory activity of 2 extracts from U. tomentosa when tested in mouse paw edema 15 ; however, CNS pathways such as serotonin receptors may also be involved. 16 Induced lung inflammation was reduced in mice pretreated with U. tomentosa bark extract. 17

Clinical data

Limited clinical studies suggest an anti-inflammatory action of cat's claw in osteoarthritis. 18 , 19 A small trial (N = 45) found improved subjective measures of pain with cat's claw; however, other objective measures were not significantly altered. Adverse effects were comparable with placebo. 20 In another small randomized trial (N = 40), U. tomentosa extract resulted in a reduction in the number of painful joints in patients with rheumatoid arthritis compared with placebo. 21

Cancer

Experimental studies have shown antiproliferative (antimitotic) and apoptotic activity of extracts of U. tomentosa . Cell lines evaluated include human leukemic 22 , 23 ; lymphoma 3 , 7 ; lung, cervical, and colon carcinoma 24 ; as well as neuroblastoma and glioma. 25 A protective effect was demonstrated in vitro against ultraviolet damage of skin cells. 26 Different preparations of U. tomentosa contain different alkaloids and result in varying cellular responses that may be related to antioxidant action on signaling pathways. 3 , 7 , 22 , 26 , 27 Extracts of U. guianensis and U. rhynchophylla containing uncarine triterpenes have also been evaluated for their cytotoxic effects. 7 , 28

Animal data

Studies in animal rodent models have shown a reduction in tumor growth with use of extracts of U. tomentosa . 24

Clinical data

Clinical studies are lacking. However, one ex vivo study using human leukemic cells obtained from children demonstrated an increased survival when exposed to extracts of U. tomentosa ; therefore, caution is advised. 29

Other effects
Antimicrobial activity

Alkaloidal extracts of U. tomentosa have shown in vitro antiviral activity against the vesicular stomatitis virus, rhinovirus, and Dengue virus. 30 , 31 Antibacterial activity has been demonstrated in vitro to human oral pathogens, such as S. mutans and S. aureus , but not C. albicans or P. aeruginosa . 32 Clinical studies are lacking.

Cardiovascular effects

Older data from in vitro and animal studies suggested hypotensive, diuretic, and vasorelaxant activity of rhynchophylline, mytraphylline, and gambirine. 9 , 33 , 34 , 35 However, clinical studies are lacking.

CNS

Although the mechanism of action remains unclear, pteropodine and isopteropodine may increase the affinity of agonists or act as positive modulators of muscarinic M 1 and 5-HT 2 receptors, improving impaired cognitive processes. 36 In vitro binding of mitraphylline to amyloid protein 37 and an apparent improvement in functioning in amyloid precursor protein transgenic mice by Yokukansan (a combination preparation containing Uncaria hook) 38 suggest investigative potential as Alzheimer disease therapeutic agents. Yokukansan and U. rynchophylla have been evaluated for other CNS effects, including epilepsy. 39 , 40 , 41 , 42

Estrogen

Studies are conflicting on the effect of U. tomentosa extracts on estrogen receptors. 43 In rats with induced endometriosis, cat's claw preparations decreased the volume of foci and exerted possible anti-inflammatory and immune-modulatory activity. 44

Immunomodulating

All individual alkaloids of U. tomentosa , with the exception of rhynchophylline and mitraphylline, have immunostimulant properties 45 and the ability to enhance phagocytosis in vitro. Researchers have shown that pteropodine and isopteropodine have immune-stimulating effects. 46 Controlled clinical trials are lacking; however, an uncontrolled study suggested a positive effect on lymphocytes in HIV-positive individuals. 8

Dosage

One gram of root bark given 2 to 3 times daily is a typical dose, while 20 to 30 mg of a root bark extract has been recommended. 2 Clinical trials are generally lacking to support appropriate dosages. A standardized extract based on a particular chemotype of this species containing 8% to 10% carboxy alkyl esters and less than 0.5% oxindole alkaloids has been used in clinical studies in doses of 250 to 300 mg. 47 , 48

Pregnancy/Lactation

Information regarding safety and efficacy during pregnancy and lactation is lacking. U. tomentosa has traditionally been used as an emmenagogue. 2 , 8

Interactions

Case reports are generally lacking; however, a report of an interaction with protease inhibitors exists. Theoretical interactions exist based on in vitro inhibition of cytochrome P450 3A4 isoenzyme, and may include protease inhibitors, nonnucleoside reverse transcriptase inhibitors, cyclosporine, benzodiazepines, and calcium channel blockers. Interactions with anticoagulants and chemotherapeutic agents have also been suggested. 8 , 49 , 50

Adverse Reactions

Case reports of adverse events are rare, although information is lacking. The American Herbal Products Association rates Uncaria preparations as class 4 (lack of data to support safety). 8 , 20

Possible adverse effects include GI complaints (nausea, diarrhea, stomach discomfort), renal effects (a case report of acute renal failure exists), hormonal effects (in vitro data suggest extracts may interact with estrogen-receptor binding sites), neuropathy (a case report of worsened Parkinson disease symptoms exists), and an increased risk of bleeding with anticoagulant therapy. 8 , 51

It is therefore recommended that Uncaria -containing products be avoided around before and after surgery, by those using immunosuppressant therapy, and in children due to lack of safety data. 8

Toxicology

Historical ethnomedicinal evidence and current use by consumers suggest low toxicity; however, toxicological studies are limited. In rats, the median lethal dose of a single dose of a water extract of U. tomentosa was determined to be greater than 8 g/kg. In humans, there were no toxic adverse effects observed at a repeated dose of 350 mg/day for 6 consecutive weeks. 2 , 52 , 53 , 54

Bibliography

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25. García Prado E, García Gimenez MD, De la Puerta Vázquez R, Espartero Sánchez JL, Sáenz Rodríguez MT. Antiproliferative effects of mitraphylline, a pentacyclic oxindole alkaloid of Uncaria tomentosa on human glioma and neuroblastoma cell lines. Phytomedicine . 2007;14(4):280-284.
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41. Lo WY, Tsai FJ, Liu CH, et al. Uncaria rhynchophylla upregulates the expression of MIF and cyclophilin A in kainic acid-induced epilepsy rats: A proteomic analysis. Am J Chin Med . 2010;38(4):745-759.
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49. López Galera RM, Ribera Pascuet E, Esteban Mur JI, Montoro Ronsano JB, Juárez Giménez JC. Interaction between cat's claw and protease inhibitors atazanavir, ritonavir and saquinavir. Eur J Clin Pharmacol . 2008;64(12):1235-1236.
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51. Vogel JH, Bolling SF, Costello RB, et al; American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (Writing Committee to develop an Expert Consensus Document on Complementary and Integrative Medicine). Integrating complementary medicine into cardiovascular medicine. A report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents (Writing Committee to Develop an Expert Consensus Document on Complementary and Integrative Medicine). J Am Coll Cardiol . 2005;46(1):184-221.
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