Cat's Claw / Uncaria Tomentosa (Wild DC)

Common Name:
Cat's Claw

Other names:
Deixa, garabato, garabato amarillo, garabato colorado, garra gavilán, jipotatsa, kug kukjaqui, micho-mentis, paotati-mosha, samento, toroñ, tsachik, uncucha, unganangi, cat's claw of the highlands.

Botanical description:
It is a large climbing or creeping vine over 40 m long. It can be 20 m high and reach around 20 cm of diameter. Its bark is brown, with longitudinal fissures and persistent rhytidome. The internal part has a slightly dusty fibrous and laminar texture: a characteristic ferruginous dust. It has flowing-consistency watery secretions and extremely astringent taste. Moreover, it has quadrangular section terminal branches, with yellowish green internal medulla, glabra and small lance-shaped leaves. The older branches have a couple of curved-straight thorns, not twisted and sharp-pointed, with woody consistency, about 8 to 20 mm long and 3 to 6 mm wide. 
Its leaves are simple, opposite and distichous, oblong, oblong-ovate or elliptical-vaulted, 7,5 to 17 cm long and 4,3 to 12 cm wide, with the entire border slightly sinuate, with rarely acuminate acute apex, round and/or cordate base and membranous consistency; with oblique pinnate venation and secondary veins having eight to ten pairs. The petiole is 8 to 28 mm long and 1,2 to 2,5 mm wide, it is dark green on the face and pale green on the back. In this zone, there are tiny fine woolly hairs called tomentum -from which derives the name tomentosa- being dense and closely matted in all its extension. In other occasions, they only appear in the veins or nervation of the back. It also has deltoid-shaped inter-petiole stipules which are about 6 to 12 mm long and 4 to 8 mm wide. 
Its flowers appear is raceme inflorescences (chapter), like globoid head tops. Their diameter measures 1,5 to 2,8 cm. The inflorescence can be 7 to 18 cm long. Its flowers are small, hermaphroditic, actinomorphic and sessile; its calyx is tubular, with 5 sharp-pointed lobules, with villous hairs in the edge of the lobules, 1 to 1,5 mm long. The corolla is infundibuliform, with five round yellow lobules, densely pubescent in the external part and almost glabrous in the internal part, 7 to 13 mm long. The hypanthium is tubular and the calyx and corolla coincide at this point. The androecium has five stamens congenitally joined to the throat of the corolla and alternate petals. The anthers are oblong, with 1 to 1,2 mm-long prolonged and diverging bases. The gyneceum has an inferior linear-style bicarpellary divided ovary, until 4 mm long. The ellipsoid stigma is 0,5 mm long.
The fruit is dry, dehiscent and polysperm. It has two valves; it is ellipsoid and ovate-oblong. It measures 5 to 9 mm in length and 2 to 6 mm in diameter. Its calyx is persistent and crescent. The hairy dry carpels are mostly white. 
The seeds are fusiform, with membranous-like wings: one extreme is linear and the other one is deeply cleft. They have two aristas and measure 2,5 to 4 mm in length and 0,5 to 0,8 mm in width (Obregón 1995: 27-29; Zavala et al. 1997: 45-54).

Life Behavior:
It is a climbing vine found in primary forest, usually in the crown of trees measuring 20 to 30 m in height. The plant reaches over 40 m in length.

Chemical Composition:

• Alkaloids (rhynchophylline, isorhynchophylline, Isomitraphylline, dihydrocorynantheine, uncarine F, hirsuteine, hirsutine, uncarine C and uncarine E) are found in the leaves.
   

• Alkaloides (rhynchophylline, isorhynchophylline, Isomitraphylline, dihydrocorynantheine, uncarine F, uncarine C, uncarine E, hirsuteine and hirsutine), as well as isopentane compounds (three polyhydroxilated three-terpenes) and glycosides (three glycosides of the quinovic acid) are found in the leaves.

Actions:
Cat's Claw has immunostimulant (stimulates and strengthens the body's defenses) anti-inflammatory and cytostatic (stops the growth and development of tumor-like cells) properties. It has a contraceptive effect when used in high concentrations. It has an anti-inflammatory and oncostatic effect in comparatively low concentrations.

Distribution:
This species can be found from Panama and Guyana until Bolivia and Brazil. In our country, we find it in the low Amazonian jungle, until 800 m a.s.l.

Traditional Uses:

	As anticarcinogenic: The root and bark infusion is consumed.
	Against arthritis: The root and stem infusion is used.
	Anti-inflammatory action: The use of the bark infusion is recommended.
	Diuretic action: The bark infusion is consumed.

Pharmacological Information:
Action in cell cultures
The plant's water extract, alkaloid fractions and unique alkaloids capacity to increase the phagocytes was analyzed in the granulocyte test according to Brandt and in the chemical luminescense test. It was demonstrated that it is necessary to reduce the increasing activity of the phagocytes on the isopteropodine and alkaloid pteropodine, with which a 66% increase of the phagocytes is achieved; that is, 27% in a 27 mg/ml concentration (3; 16; 35; 36).
Research has been conducted on the antitumorous effect of the water extract, of the alkaloid fractions and of the unique alkaloids of the plant in different tumorous cellular lines.
Different degrees of inhibitory influence of the test substances proliferation were obtained in all the cellular lines. This influence, which was achieved with a 70 mg/mL per 100% concentration (2; 3; 15; 16; 24; 37) was more pronounced with the isopteropodine and pteropodine monosubstances.
The protecting effect of the substances against the hemolyzing influence of the yperite nitrogen (10-4 M) and valinomicine (2,5 x 10-7 M) was analyzed with a total extract (0,3 mg/mL) in erythrocyte concentrates. A 50% decrease of the hemolysis against the controls (4; 5; 6) was observed at this point. 
The antiviral effect against the simplex herpes -1 and -2 was analyzed with a total extract in vero and hep-2 cells. The minimum inhibitory concentration (=MIC, dose in which the apparition of the cytopathic effect is decreased by 25%) is 100 g/mL for vero and 330 g/mL for hep-2 (22).
The inhibitory effect of the total extract on the reversible transcriptase activity was analyzed. The medium concentration (=ID50, concentration in which the activity was decreased by 50%) became evident at 60 g/mL (1).

Toxicological Information:
Acute toxicity
The acute toxicity of the watery lyophilized extract was tested at the Huntington research center. The test substance was orally administered in a suspension at 40% in thick tragacanth at 0,5%, through a esophageal sound. The maximum volume of the application was 40 ml/kg BW (17).

Results:
About five animals of the study group, male and female, died with the tested dose of 16g/kg BW. A lower dose was not tested. Lethargy and piloerection appeared after the application. They died within four hours after the administration. The dead animals showed stomachic and intestinal hemorrhage, as well as liver and spleen discoloration. 
The surviving animals resisted five days. The weight gain of the surviving animals was similar to the weight gain of the control group. The autopsy showed a discreet result. In the two dead animals, the hemorrhage observed in the stomach-intestinal tract must have been consequence of the high concentration (40%) together with the great volume of the dose (1ml/25g); thus, the observation had little importance for the therapeutic application. In a later research, the oral and intraperitoneal toxicity of the total extract and of the pure alkaloid compound was tested in mice (16).
The total extract was administered orally at a dose of up to 5g/kg, and parenterally up to 2g/kg. In the pure alkaloid compound, the maximum oral or intraperitoneal dose was 2g/kg or 1g/kg.
The animals continued to be under observation for fourteen days. No difference was noticed in the normal behavior.

Conclusion: 
In a single dose, the Uncaria tomentosa extract employed in the research with animals seems to be practically atoxic. One of the five animals died with a 16g/kg dose.
A maximum 2 g/kg dose of the extract was applied intraperitoneally. The alkaloid fraction tested in a maximum 1g/kg dose was not toxic.

Subacute Toxicity
An oral toxicity study was conducted in rats during 28 days In the Uepp Room of Scantox. The study consisted in a OED-straight line limit test for chemical products Nº 407, section 4, with a 1000 mg/kg dose of the Uncaria tomentosa extract titrate.
The substance was diluted in water (100 mg/ml) and daily applied through an esophageal probe. The control and Verum groups were formed by ten Wistar rats, among males and females, respectively.
The evolution of the corporal weight, the food intake, the hematology -including blood count-, the thrombosplastin time, the creatin and the alaninaminotransferase in blood were analyzed. 

Moreover, changes in the behavior of the animals and the symptoms of the illness were observed.
By the end of the treatment, the autopsy was performed on the animals and the weight of organs such as kidneys, liver, suprarenal capsules and testicles was registered. The kidneys, liver, suprarenal capsules, testicles, heart and spleen, as well as all the organs showing macroscopic differences, were also histologically studied.

Results:
No clinical or behavioral differences were observed. No deaths took place during the observation period. The evolution of the weight and need for food were the same as in the control group.
The hematological parameters were discreet, except in the case of the lymphocytes and granulocytes. While the lymphocytes in the Verum group were slightly high, the percentage of neutrophil granulocytes was significantly lower than in the control group. Although all the values suffered changes, they were within the normal limits.
A slight increase of phagocyte esterases was recognized in the phagocyte test in the Verum group. The phagocyte activity in the males was higher than in the females of both groups. 
There were no changes in the creatinin nor in the alaninaminotransferase.
In the macroscopic level, only a slight color change was observed in the kidneys of four males. This phenomenon was observed in the females of the control and Verum groups.
The absolute weight of the organs remained almost without variation. Regarding the relative weight of the organs, a slight increase in the values of the kidneys of the Verum group was observed. However, the kidneys showed no histological variation.

Conclusion:
It was demonstrated that the Uncaria tomentosa extract orally administered to rats on a daily basis in a 1000 mg/kg dose for 28 days is practically atoxic.