Cat's claw

Uncaria Tomentosa (of the family Rubiaceae) is one of two herbs, the other being Uncaria guianensis, that have the common name of Cat's Claw; these two herbs are vines that grow in the Amazon forest and have traditional usage as anti-inflammatory agents,^[1] with other traditionally claimed benefits extending to arthritis, bursitis, lupus, chronic fatigue syndrome, and both stomach and intestine disorders.^[2] This article describes the properties of Uncaria Tomentosa unless otherwise specified.

There are two known chemotypes of Uncaria Tomentosa, which share the species name but may have differing chemical composition; due to this, benefits attributed to alkaloids may be variable due to which chemotype is being consumed.^[3]

The components of Uncaria Tomentosa are:

• Mitraphylline and Isomitraphylline, seen as the main bioactives and usually present in older leaves or the stem bark^[3]
• Rhynchophylline and Isorhynchophylline^[4]
• Isopteropodine^[4]
• Uncarine C (aka. Pteropodine), Uncarine D (Speciophylline)^[3] and Uncarine F^[4]
• Alkaloids Hirsutine, Hirsuteine, Dihydrocorynantheine and Corynantheine at times in young leaves^[3]
• (Polyhydroxylated) Triterpenes Uncaric Acid, Floridic Acid, and 3β,6β,19α-trihydroxy-23-oxo-urs-12-en-28-oic acid^[5] and two other unnamed triterpenoids in the stem^[6]
• The triterpenoid Quinivic Acid (around 0.11%^[7]) and numerous glycosides (may total around 0.31%^[7]),^[8][9][10] as well as common triterpenoids ursolic acid and Oleanolic acid
• Pyroquinovic acid and its glycosides, Tomentosides A and B (known as 27-nortriterpene glycosides)^[11]
• Quinic Acid^[12]
• Glucoindole alkaloids 3α-Dihydrocadambine and Dolichantoside^[4] as well as 3,4-dehydro-5- carboxystrictosidine,^[13] 5α-carboxystrictosidine,^[14] and Lyaloside^[13]
• Epicatechin and Cinchonain Ia and Ib, known as procyanidines (as chains of them form Procyanidins)^[15] as well as the Procyanidins A1, B1, B2, and B4^[16]

The entire structural class of pentacyclic triterpenoids may be relevant (many named 'Uncarines' after the Uncaria genera), with Mitraphylline being most relevant to Cat's Claw; the structurally class of Glucoindole alkaloids are also plentiful

With some bioactives found in Uncaria Guianensis (possibly related to supplementation) being:

• Also has a Mitraphylline and Isomitraphylline content^[17]
• Rhynchophylline and Isorhynchophylline,^[3] except higher levels than that usually seen in Tomentosa^[17]
• Corynoxeine and Isocorynoxeine^[3]
• Quinovic acid as four glycosides (Glucose(3-1)Fucose with a Galactose, Fucose, Quinovose, and Fucose with a Galactose)^[18]

The sum of all alkaloids appears to vary from 0.156 to 0.962%,^[19] and may vary widely between the two chemotypes of Uncaria Tomentosa (with one higher in pentacyclic triterpenoids and the other tetracyclic).^[3] Oddly, one study has suggested that a beneficial effect of pentacyclic oxindole alkaloids (promotion of leukocytes) is effectively antagonized by tetracyclic alkaloids.^[20]

Both main species of Cat's Claw (tomentosa and guianensis) appear to share anti-inflammatory and anti-oxidant properties.^[21][22][23]

One study using isolated Quinic Acid (component of Cat's Claw, the Cinchonia genera, and Coffee) was found to prolong life of C.Elegans under heat (17.8%) and oxidative (29.7%) stress and extend the lifespan of C.Elegans by 15.7% independent of stress; with the latter thought to be related to induction of DAF-16.^[12] An increase in DNA repair rates has also been noted in rats who were irradiated (to damage DNA) and then observed over 3 hours, where both single strand and double strand breaks over 3 hours were reduced in a dose-dependent manner with 40-80mg/kg oral intake;^[24] this increased rate of DNA repair has been noted in human immune cells undergoing chemotherapy, where damage assessed by Comet Assay was reduced more than half.^[25]

One study in erythrocytes (red blood cells) noted that 250ug/mL of Cat's Claw (both ethanolic and aqueous extracts of the leaves and stems) were able to preserve Catalase activity in the presence of the pesticide 2,4-D-Na and its metabolites(2,4-DCP, Catechol)^[26] that are known to reduce catalase activity;^[27] these protective effects against 2,4-D-Na were noted elsewhere,^[28] although a failure to exert anti-oxidative effects against organic radicals, such as semiquinones, was noted at 5-500ug/mL.^[28]

Erythrocyte structural changes have been noted with concentrations of up to 250ug/mL, but were not seen as adverse (benign structural changes occur when polyphenolics embed themselves within a cellular membrane^[29][30]); higher concentrations of 50-100ppm induced considerable morphological changes, however.^[31] No Cat's Claw induced hemolysis is noted up to 500ug/mL^[31][28]

Studies conducted in humans include 350mg of Cat's Claw for 6 weeks which failed to alter any serum reading related to red blood cells^[32] and one trial using Uncaria Guianensis failing to note alterations in hematocrit or haemoglobin.^[33]

Mitraphylline (when fed to mice at 30mg/kg for 3 days) is able to reduce LPS-induced TNF-α release by 50%, IL-1α and IL-1β by 70%; this slightly underperformed relative to 2mg/kg Dexamethasone (active control).^[34] IL-4 was also reduced 40% and IL-17 by 50%.^[34]

Mitraphylline may be the active ingredient in suppressing inflammatory cytokine release from activated immune cells

Cat's Claw appears to be one of the more popular herbal supplements recommended against inflammatory joint diseases.^[1]

In isolated chondrocytes, 10μg/mL Uncaria tomentosa (Vincaria brand name) can increase IGF-1 levels by 67% when incubated over 48 hours and preserve up to half of IGF-1 levels when IL-1β is introduced;^[35] IL-1β and other proinflammatory cytokines tend to suppress IGF-1 via silencing genomic transcription.^[36][37]

On normal blood mononuclear cells, concentrations between 50-250ug/mL of either the ethanolic or aqueous extracts appear to dose-dependently induce apoptosis, although only the ethanolic bark extract at 250ug/mL exceeded 10% apoptosis, although an increase in cell granularity was seen at 50ug/mL.^[38]

One study noted that the pentacyclic oxindoles were able to induce endothelial release of factors (not named in study) to promote production of lymphocytes and weakly activated B and T cells while suppressing lymphoblasts;^[20] these effects were antagonized by tetracyclic oxindole alkaloids.^[20]

When human volunteers (n=4) are given Cat's Claw water extract (C-MED-100) at 350mg daily for 6 weeks, that a small increase in white blood cell count (6.60+/-0.35 to 7.18+/-0.50 WBC/10⁹/L; 8.7% increase).^[24] These researched followed up this small study with a proper trial, where 250-350mg of C-MED-100 increase leukocyte count over 6 weeks in healthy volunteers.^[32]

A trial in women with breast cancer undergoing chemotherapy noted that the reductions in Leukocytes and Lymphocytes were attenuated, while levels of Neutrophils and Monocytes actually exceeded baseline levels despite chemotherapy.^[25] This may be related to prolonging the survival of leukocytes (noted in vivo^[39]), meaning the increase is indirect through reduced apoptosis of immune cells.

Cat's Claw is investigating for adjunct therapy (to be taken alongside chemotherapy to either enhance actions or attenuate side effects) due to its immunostimulating properties; this was first evidence when rats given Doxorubicin had lower rates of Leukopenia (depletion of leukocytes) when given Cat's Claw concurrently.^[40]

In persons with breast cancer undergoing FAC Therapy (Fluorouracil, Doxorubicin, Cyclophosphamide) noted that the addition of 300mg Cat's Claw extract (70% ethanolic extract with 2.57% pentacyclic oxindole alkaloids) was able to reduce the degree of neutropenia and improve DNA repair relative to FAC paired with placebo.^[25] This study noted that the reduction of immune cells over 6 cycles of chemotherapy in control (Leukocytes by 52%, Neutrophils by 70%, Lymphocytes by 44%, and Monocytes by 8%) was attenuated by 39% and 6.5% (Leukocytes and Lymphocytes) with both Neutrophils and Monocytes increasing to levels higher than baseline despite chemotherapy.^[25] This is seen as promising since a Neutrophil count below 500cells/mm^3[41] is the point when chemotherapy is discontinued on account of Neutropenia and excessive risk to the patient.^[42] Another study in persons undergoing colon cancer chemotherapy (Fluorouracil/leucovorin with oxaliplatin; also underwent colectomy) with 300mg Uncaria Tomentosa noted a trend to increase neurophil count after six cycles but this failed to reach statistical significance, with all cycles prior to the end of the study also failing to note significant differences.^[43]

May have potential as an adjunct therapy during chemotherapy to reduce the suppression on the immune system and genomic damage, seems to influence neutrophils more than other types of immune cells and help with Neutropenia. Despite human studies, it is still preliminary as the main bioactive is not yet known and it doesn't appear to be reliable

Cat's Claw appears to have anti-estrogenic properties, as in a concentration dependent manner in vitro between 10-20mcg Cat's Claw noncompetitively inhibits the estrogen receptor (possibly by preventing formation of estrogen receptor complexes required for genomic signalling) with the higher concentration (20mcg) reducing binding of estradiol by 47.2%.^[44] This was lesser than the active control of 20mcg Tamoxifen, a direct antagonist inhibiting 69.3% of signalling.^[44]

Lepidium meyenii, known as Maca, is able to increase IGF-1 levels in human chondrocytes by approximately 2.7 fold when a concentration of 50μg/mL is used; coadministration of 10μg/mL Cat's Claw increases this induction to 3.8 fold despite having weak effects in isolation.^[35] The partial inhibition of IL-1β induced reductions in IGF-1 by both Maca and Cat's Claw (50 and 10μg/mL) is nearly absolute with the combination and similar normalizing effects were seen on IL-1β induced GAG release.^[35]

At least one in vitro study suggests that Maca and Cat's Claw may have additive benefits in regards to osteoarthritis; synergism not yet demonstrated nor any trials in living systems

The LD₅₀ of Cat's Claw water extract in rats appears to be greater than 8g/kg.^[24]

In a rat model of endometriosis, Cat's Claw (2.8-4mg/kg bodyweight) was able to reduce the rate of growth of endometrial cells from primary to mature (seen in 100% of control) to 10%, halting 90% of rats in the primary stage of cell growth; this was comparable to the active control of Leuprolide Acetate at 1mg/kg.^[45] Mature Corpus Luteum was similarly reduced from 100% in control to 10% in Cat's Claw, with the percentage of atrophied Corpus Luteums increased to 70%. Due to these mechanisms the authors hypothesized that Uncaria Tomentosa has contraceptive properties,^[45] as the changes are similar to those observed after intake of well known contraceptives.^[46]