Cat's Claw Research Articles

ChemInform Abstract: Oxindole: A Chemical Prism Carrying Plethora of Therapeutic Benefits

AbstractReview: 149 refs.

Dietary supplement interactions with antiretrovirals: a systematic review.

Many patients who take antiretroviral drugs also take alternative therapies including dietary supplements. Some drug-supplement combinations may result in clinically meaningful interactions. We aimed to investigate the evidence for dietary supplement interactions with antiretrovirals. A systematic review was conducted using multiple resources including PubMed, Natural Medicine Comprehensive Database, The Review of Natural Products, and Google Scholar. All human studies or case reports evaluating an interaction between a dietary supplement and an antiretroviral were selected for inclusion. Twenty-eight pharmacokinetic studies and case-series/case reports were selected for inclusion. Calcium carbonate, ferrous fumarate, some forms of ginkgo, some forms of garlic, some forms of milk thistle, St. John's wort, vitamin C, zinc sulfate, and multivitamins were all found to significantly decrease the levels of selected antiretrovirals and should be avoided in patients taking these antiretrovirals. Cat's claw and evening primrose oil were found to significantly increase the levels of antiretrovirals and patients should be monitored for adverse effects while taking these dietary supplements with antiretrovirals. This systematic review shows the importance of screening all human immunodeficiency virus patients for dietary supplement use to prevent treatment failure or adverse effects related to an interaction.

Uncaria tomentosa extract alters the catabolism of adenine nucleotides and expression of ecto-5′-nucleotidase/CD73 and P2X7 and A1 receptors in the MDA-MB-231 cell line

Ethopharmacological relevanceUncaria tomentosa (Willd.) DC. (Rubiaceae) (Ut), also known as cat's claw, is a woody liana widely spread throughout the Amazon rainforest of Central and South America, containing many chemical constituents such as oxindole alkaloids, which are responsible for various biological activities. Since ancient times, the indigenous people of Peru have used it as a bark infusion for the treatment of a wide range of health problems gastric ulcers, arthritis and rheumatism. Recently, Ut is distributed worldwide and used as an immunomodulatory and anti-inflammatory herbal remedy. Additionally, U. tomentosa also has antitumural activity. However, little is known about the action of U. tomentosa on the purinergic system mechanisms, which is involved in tumor progression. Aim of the studyConsidering the pharmacological properties of U. tomentosa, we sought to evaluate the hydroalcoholic extract U tomentosa is able to influence the purinergic system in breast cancer cells, MDA-MB-231. Through the activity and expression of ectonucleotidases (NTPDase – CD39; Ecto-5′-nucleotidase – CD73) and purinergic repceptores (P2X7 and A1). Materials and methodsA hydroalcoholic extract was prepared in two concentrations, 250 and 500μg/mL. (Ut250; Ut500). The effect of these concentrations on the activity and expression of ectonucleotidases, as well as on the density of purinergic receptors were investigated in MDA-MB-231 breast cancer cells. Cells were treated with the hydroalcoholic extract of Uncaria tomentosa and/or doxorubicin (Doxo 1μM; Ut250+Doxo; Ut500+Doxo) for 24h. ResultsAlthough the results were not significant for the hydrolysis of the ATP, they presented an increase in the ADP hydrolysis in the Ut500+Doxo group when compared to the control group. Additionally, the activity of 5′-nucleotidase was inhibited in all groups when compared with the untreated group of cells. Inhibition of the enzyme was more evident in groups with U. tomentosa per se. The expression of CD39 was increased in the Ut250 and Ut250+Doxo groups when compared to the control group. No changes were found in the CD73 expression. Furthermore, a reduction in the density of the P2X7 receptor in all treated groups was detected. On the other hand, the density of the A1 receptor increased in all groups compared to the control group, with the exception of the Ut500+Doxo group. ConclusionTherefore, we conclude that hydroalcoholic extract of U. tomentosa may be responsible for the reduction of adenosine levels in the extracellular medium, which accelerates tumor progression. Interestingly, the dysregulation of A1 and P2X7 receptors in the MDA-MB-231 cells exacerbate the proliferation of this cells and U. tomentosa treatment may be stimulate the antitumor activity of adenosine A1 receptor and control the P2X7 effects. Our study demonstrates the significant participation of purinergic pathway in the regulation of MDA-MB-231 progression; additionally, U. tomentosa treatment alone or combined with chemotherapy may favor the action of doxorubicin.

Genotoxicity and cytotoxicity of oxindole alkaloids from Uncaria tomentosa (cat's claw): Chemotype relevance

Ethnopharmacological relevanceUncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) or cat's claw is a climber vine from the South American rainforest used in folk medicine for cancer treatment. Its antitumor activity has been mostly ascribed to pentacyclic oxindole alkaloids (POA) from stem bark and leaves while the activity of tetracyclic oxindole alkaloids (TOA) remains unknown. In recent times, the occurrence of three chemotypes based on its oxindole alkaloid profile was noticed in U. tomentosa, namely, chemotype I (POA cis D/E ring junction); chemotype II (POA trans D/E ring junction) or chemotype III (TOA). Consequently, the relationship between the chemotype and cytotoxic and genotoxic activities deserves attention. Aim of the studyTo evaluate the influence of cat's claw chemotypes on genotoxicity and cytotoxicity against non malignant and malignant human cell line models. Material and methodsFour authentic stem bark cat's claw samples (SI-SIV) and two leaf samples (LII and LIII) were analyzed by HPLC-PDA, properly extracted and fractioned by ion-exchange to obtain oxindole alkaloid purified fractions (OAPFs). The freeze-dried fractions were assayed for genotoxicity and cytotoxicity against human leukocytes (non malignant cell line) by the micronuclei frequency method and the alkaline comet DNA assay, and the trypan blue method, respectively. Moreover, the cytotoxicity of each OAPF was evaluated against a human bladder cancer cell line (T24) and human glioblastoma cell line (U-251-MG) by MTT method (malignant cell lines). Additionally, the isomerization of oxindole alkaloids throughout the course of cell incubation was monitored by HPLC-PDA. ResultsBased on HPLC-PDA analyses, sample SI was characterized as chemotype I, while samples SII and LII were characterized as chemotype II, and samples SIII, SIV and LIII as chemotype III. The chemotypes showed comparable cytotoxic activity toward malignant cell lines (T24 and U-251-MG) unlike human leukocytes (non malignant cell line), where this activity was clearly distinct. Chemotype II (POA trans D/E ring junction) showed a higher selectivity index (SI) against malignant cells (SI=1.11–3.04) than chemotype I (SI=0.10−0.19) and III (SI=0.21–0.57). No important genotoxic potential was found by micronuclei frequency and alkaline comet DNA assays. Despite the isomerization of oxindole alkaloids during the cell incubation, the chemotype of the cat's claw samples remained unchanged. ConclusionCat's claw chemotypes showed different selectivity against human malignant cells, so that the correct identification of each chemotype seems to be important to better understand its antitumor potential.

Uncaria tomentosa increases growth and immune activity in Oreochromis niloticus challenged with Streptococcus agalactiae.

Cat's claw (Uncaria tomentosa) is an Amazon herb using in native cultures in Peru. In mammals, it has been described several effects of this herb. However, this is the first report of its use on the diet of fish. The aim of this study was to determinate the effect of this plant on the growth and immune activity in Oreochromis niloticus. Nile tilapia (81.3 ± 4.5 g) were distributed into 5 groups and supplemented with 0 (non-supplement fish), 75, 150, 300, and 450 mg of U. tomentosa.kg(-1) of diet for a period of 28 days. Fish were inoculated in the swim bladder with inactivated Streptococcus agalactiae and samples were taken at 6, 24, and 48 h post inoculation (HPI). Dose dependent increases were noted in some of the evaluated times of thrombocytes and white blood cells counts (WBC) in blood and exudate, burst respiratory activity, lysozyme activity, melanomacrophage centers count (MMCs), villi length, IgM by immunohistochemistry in splenic tissue, and unexpectedly on growth parameters. However, dietary supplementation of this herb did not affect red blood cells count (RBC), hemoglobin, and there were no observed histological lesions in gills, intestine, spleen, and liver. The current results demonstrate for the first time that U. tomentosa can stimulate fish immunity and improve growth performance in Nile tilapia.

Uncaria tomentosa Gel against Denture Stomatitis: Clinical Report.

The objective of this study is to report the clinical use of 2% Uncaria tomentosa gel against denture stomatitis (DS) as an alternative treatment. The patient was a 65-year-old, denture-wearing woman. At the clinical examination, her palate showed hyperplasic and erythematous mucosa indicating DS type II. DS is a chronic oral disease that affects denture wearers. It occurs as an inflammatory reaction in denture-wearing patients under maxillary prostheses. Candida albicans has been reported as the principal etiological agent. An alternative treatment, the topical application of a gel of 2% U. tomentosa three times a day for 1 week was given to the patient. After 1 week of this treatment, she had significantly reduced signs of the disease. Despite the existence of a great number of antifungal agents, treatment failure is observed frequently. Phytotherapy is becoming more popular worldwide. Currently, the most promising medicinal Amazonian herb is U. tomentosa (Willd.) DC., known as Cat's Claw. Studies of the chemical and pharmacological properties of this medicinal plant have allowed researchers to develop indications for its use. This report demonstrates the effectiveness of U. tomentosa against DS.

CHEMICAL COMPOSITION VARIABILITY IN THEUncaria tomentosa(cat's claw) WILD POPULATION

Uncaria tomentosa (cat's claw) is a vine widely distributed throughout the South-American rainforest. Many studies investigating the chemical composition of cat's claw have focused on the pentacyclic (POA) and tetracyclic oxindole alkaloids (TOA), quinovic acid glycosides (QAG), and polyphenols (PPH). Nevertheless, it is still uncertain how environmental factors affect chemical groups. The aim of this work was to better understand the influence of environmental factors (geographic origin, altitude, and season) on cat's claw chemical composition. Stem bark, branches and leaf samples were extracted and analyzed by HPLC-PDA. The data obtained were explored by multivariate analysis (HCA and PCA). Higher amounts of oxindole alkaloids and PPH were found in leaves, followed by stem bark and branches. No clear relationship was verified among geographic origin or altitude and chemical composition, which remained unchanged regardless of season (dry or rainy). However, three oxindole alkaloid chemotypes were clearly recognized: chemotype I (POA with cis D/E ring junction); chemotype II (POA with trans D/E ring junction); and chemotype III (TOA). Thus, environmental factors appear to have only a minor influence on the chemical heterogeneity of the cat's claw wild population. Nevertheless, the occurrence of different chemotypes based on alkaloid profiles seems to be clear.

Studies on the mechanisms of tumour inhibition by fractions from two species of Cat's Claw

South America has two predominant species of Cat's Claw (Uña de Gato), Uncaria tomentosa and U. guianensis, which are used in traditional medicine to treat inflammation and cancer. We have shown that their anti-tumour activity may be due, at least in part, to a reduction in pro-tumoural inflammatory processes in the tumour microenvironment, specifically to a reduction in inflammatory mediators (TNF, IL-6, nitric oxide and prostaglandins) and in infiltration by inflammatory cells of the primary tumour [1]. The aim of this study was to determine whether the two active subfractions, Sam A1 from U. tomentosa and Ug AIV from U. guianensis, also inhibited two other key processes involved in tumour growth and metastasis, specifically cell-cell adhesion and migration. These fractions were obtained by bioassay-guided fractionation following these steps: a) extraction in ethanol, b) solid/liquid extraction in different solvents, c) size exclusion chromatography, d) high pressure liquid chromatography. Sam A1 and Ug AIV did not affect the expression of the adhesion molecules ICAM-1 or VCAM-1 in liver sinusoidal endothelial cells (LSEC) by flow cytometry nor did they alter the adhesion of fluorescent 4T1 tumour cells to LSEC in co-culture. However, both preparations reduced the migration of tumour cells (4T1) and endothelial cells (LSEC) by approximately 40% at 10 mg/ml in a 24h scratch assay. Our results indicate that the effect of the two subfractions on migration, which plays a fundamental role in tumour cell invasion and angiogenesis, may contribute to their overall antitumour activity.

Alkaloid and polyphenolic profiles of Brazilian Uncaria tomentosa leaves

The leaf alkaloidal and polyphenolic profiles from four wild Uncaria tomentosa (Willd.) DC specimens (cat's claw), harvested in different locations of the Brazilian Amazon rainforest have been analyzed. Methanol leaf extracts were treated with HCl 0.1N followed by partition with ethyl acetate to afford phenol-rich fractions. The aqueous fractions were then alkalinized with NH4OH and extracted with ethyl acetate to afford alkaloid fractions. The alkaloid fractions from three specimens showed similar HPLC-DAD profiles, with the pentacyclic oxindole alkaloids mitraphylline and isomytraphylline predominating [1]. The fourth specimen showed a distinct profile with tetracyclic oxindole alkaloids as major components as revealed by [M+H]+ ions at m/z 385 in UHPLC-MS, corroborated by diagnostic signals in 1H-NMR. Apart from the sample with a distinct alkaloidal chemotype no significant differences occurred in the phenol-rich fraction profiles revealed by TLC and HPLC-DAD. They contain mostly phenolic acid derivatives complemented by minor flavonoids. The common signal for chlorogenic acid was quantified in these phenol-rich fractions by comparison with an external standard, enabling evaluation of the linearity, detection limit and recovery. The chlorogenic acid content varied from 0.15 ± 0.01 to 0.58 ± 0.02 mg/g of dry leaves as measured at 280nm, whereas the total phenolic content varied between 147 ± 22 and 632 ± 58 µg GAE/g by Folin-Ciocalteu. This study of the chemistry of the aerial parts of the species complements earlier studies most of which have been performed on commercial alkaloid-based roots and bark materials.

CUANTIFICACIÓN DE POLIFENOLES EN HOJAS DE UN CLON DE Uncaria tomentosa (WILLD. EX SCHULT) D.C., PROVENIENTE DE TRES LOCALIDADES DE LA REGIÓN UCAYALI

Uña de gato (Uncaria tomentosa Willd. ex D.C.), de la familia Rubiaceae, es un arbusto que en el bosque toma forma de liana y del cual se utiliza, tradicional y comercialmente la corteza, debido a su actividad antiinflamatoria, antimicrobiana, inmunoestimulante, antioxidante, etc. Se ha realizado diversos estudios sobre la composición química, principalmente en corteza, abundando los estudios en el grupo de los alcaloides. El objetivo de la presente investigación se centra en la cuantificación de polifenoles totales presentes en las hojas, para lo cual se tuvo como material de estudio plantas de un mismo clon establecido en tres localidades de la región de Ucayali, Perú, con condiciones edafoclimáticas diferentes. Las muestras de hojas se recolectaron en noviembre de 2009, en las localidades de Tres de Octubre, El Porvenir y Nuevo Ucayali, de las provincias de Padre Abad y Coronel Portillo. Previo tratamiento post cosecha, se obtuvo un extracto por el método de percolación utilizando como solventes soluciones hidroalcohólicas en una relación 1:25 de hojas y solvente. Los extractos obtenidos fueron sometidos a pruebas cualitativas (marcha fitoquímica), en las que se detectaron metabolitos como alcaloides, compuestos grasos, flavonoides, azúcares, taninos condensados y saponinas, y también pruebas cuantitativas que permitieron determinar el contenido de polifenoles en el extracto y de taninos condensados presentes en las muestras.

Septic Implantation Syndrome Following Anterior Lens Capsule Disruption by Cat Claw in Three Dogs

Septic Implantation Syndrome Following Anterior Lens Capsule Disruption by Cat Claw in Three Dogs

Insights into mechanism of anticancer activity of pentacyclic oxindole alkaloids of Uncaria tomentosa by means of a computational reverse virtual screening and molecular docking approach

Alkaloid-rich extract from Uncaria tomentosa (cat's claw) has been reported to cause apoptosis in cancer lines. Oxindole pentacyclic alkaloids of the plant are responsible for this effect, yet their biological mechanism of action is not fully understood. In this work the set of these alkaloids underwent an extensive theoretical study with reverse virtual screening and molecular docking methods implemented in AutoDock, AutoDock Vina, and Molegro Virtual Docker. The results from these computa- tional methods indicate that inhibition of several important targets including dihydrofolate reductase and mouse dou- ble minute 2 homolog (MDM2) may be responsible for the biological activity of the alkaloids. The docking results also show that the alkaloids can interact with Dvl-2, Akt-2, and leukotriene A4 hydrolase. Reverse virtual screening and molecular docking are valuable tools to aid identification of protein targets for bioactive hit molecules and could guide the design of in-depth biochemical activity tests and utilization of these alkaloids in anticancer drug development.

Evaluation of in vitro absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine, 7-hydroxymitragynine, and mitraphylline.

Mitragyna speciosa (kratom) is a popular herb in Southeast Asia, which is traditionally used to treat withdrawal symptoms associated with opiate addiction. Mitragynine, 7-hydroxymitragynine, and mitraphylline are reported to be the central nervous system active alkaloids which bind to the opiate receptors. Mitraphylline is also present in the bark of Uncaria tomentosa (cat's claw). Several therapeutic properties have been reported for these compounds but limited information is available on the absorption and distribution properties. This study focuses on evaluating the absorption, distribution, metabolism, and excretion (ADME) properties of these compounds and their effect on major efflux transporter P-glycoprotein, using in vitro methods. Quantitative analysis was performed by the Q-TOF LC-MS system. Mitragynine was unstable in simulated gastric fluid with 26 % degradation but stable in simulated intestinal fluid. 7-Hydroxymitragynine degraded up to 27 % in simulated gastric fluid, which could account for its conversion to mitragynine (23 %), while only 6 % degradation was seen in simulated intestinal fluid. Mitraphylline was stable in simulated gastric fluid but unstable in simulated intestinal fluid (13.6 % degradation). Mitragynine and 7-hydroxymitragynine showed moderate permeability across Caco-2 and MDR-MDCK monolayers with no significant efflux. However, mitraphylline was subjected to efflux mediated by P-glycoprotein in both Caco-2 and MDR-MDCK monolayers. Mitragynine was found to be metabolically stable in both human liver microsomes and S9 fractions. In contrast, both 7-hydroxymitragynine and mitraphylline were metabolized by human liver microsomes with half-lives of 24 and 50 min, respectively. All three compounds exhibited high plasma protein binding (> 90 %) determined by equilibrium dialysis. Mitragynine and 7-hydroxymitragynine inhibited P-glycoprotein with EC50 values of 18.2 ± 3.6 µM and 32.4 ± 1.9 µM, respectively, determined by the calcein-AM fluorescent assay, while no inhibition was seen with mitraphylline. These data indicate the possibility of a drug interaction if mitragynine and 7-hydroxymitragynine are coadministered with drugs that are P-glycoprotein substrates.

Evaluation of different treatment methods against denture stomatitis: a randomized clinical study.

The aim of this clinical study was to determine the efficacy of Uncaria tomentosa (cat's claw) against denture stomatitis (DS). Fifty patients with DS were randomly assigned into 3 groups to receive 2% miconazole, placebo, or 2% U tomentosa gel. DS level was recorded immediately, after 1 week of treatment, and 1 week after treatment. The clinical effectiveness of each treatment was measured using Newton's criteria. Mycologic samples from palatal mucosa and prosthesis were obtained to determinate colony forming units per milliliter (CFU/mL) and fungal identification at each evaluation period. Candida species were identified with HiCrome Candida and API 20C AUX biochemical test. DS severity decreased in all groups (P < .05). A significant reduction in number of CFU/mL after 1 week (P < .05) was observed for all groups and remained after 14 days (P > .05). C albicans was the most prevalent microorganism before treatment, followed by C tropicalis, C glabrata, and C krusei, regardless of the group and time evaluated. U tomentosa gel had the same effect as 2% miconazole gel. U tomentosa gel is an effective topical adjuvant treatment for denture stomatitis.

Martynia annua: An Overview

Martynia annua belongs to family Martyniaceae is an herbaceous annual plant, spread throughout India. It is commonly known as the Cat's claw or Devil’s claw. In India, traditional healers used M. annua in the treatment of epilepsy, inflammation, sore throat, burns, itching, skin affections and tuberculosis. M. annua contains alkaloids, tannins, saponins, glycosides, flavonoids, anthocyanins, amino acid, steroids and phenols. The researcher scientifically documented various pharmacological activities such as anthelmintic, analgesic, antipyretic, antibacterial, anti convulsant, antifertility, antinociceptive, antioxidant, CNS depressant, antidiabetic and wound healing activity of this plant. The reported activities make the plant in great interest among scholars to determine the mechanism of pharmacological activities of crude extracts. Hence the review paper outlines the previous research done on M. annua.

Uncaria tomentosa Alkaloidal Fraction Reduces Paracellular Permeability, IL-8 and NS1 Production on Human Microvascular Endothelial Cells Infected with Dengue Virus

Dengue is the major Arbovirus in the world, annually causing morbidity and death. Severe dengue is associated with changes in the endothelial barrier function due to the production of inflammatory mediators by immune cells and by the endothelium. Dengue virus (DENV) replicates efficiently in human endothelial cells in vitro and elicits immune responses resulting in endothelial permeability. Uncaria tomentosa (Willd.) DC.(Rubiaceae), known as cat's claw, has been used in folk medicine for the treatment of a wide-array of symptoms, and several scientific studies reported its antiviral, immunomodulatory, anti-inflammatory and antioxidant properties. Here we infected a human lineage of dermal microvascular endothelial cells (HMEC-1) with DENV-2 and treated it with an alkaloidal fraction from U. tomentosa bark (AFUT). We showed antiviral and immunomodulatory activities of U. tomentosa by determining the NS1 antigen and IL-8 in supernatant of DENV-2 infected HMEC-1. Furthermore, by measurement of transendothelial electrical resistance (TEER) we demonstrated, for the first time, that a plant derivative contributed to the reduction of paracellular permeability in DENV-2 infected HMEC-1. We also showed that IL-8 contributed significantly to the induction of permeability. Although further investigations should be conducted before a new drug can be suggested, our in vitro data support evidence that AFUT could be potentially useful in developing a treatment for severe dengue.

The Potency of some Natural Products on Dimethyl Benz ( A ) antheracene( DMBA ) Induced Hepatotoxicity in Rats

Aim of the work:the present study was carried out to investigate the possible ameliorating effects of three herbs: hops(H) 1.5g/kg diet , rosemary(R) 5g/kg diet and cat's claw (C C) 1.7g/kg diet on hepatic toxicity induced by 7,12-Dimethyl benz(A)antheracene , a hydrocarbon involves various negative consequence for human health and ecosystems conversation .Results:in this work,48 female rats at 50 day of age were divided into 8 groups; control ,hops(H), rosemary(R), cat's claw(CC),DMBA, DMBA+H,DMBA+R and DMBA+CC groups.Results:the results indicated that a single intraperitonial (i.p) dose of DMBA (30mg/Kg b.W) caused significant decrease in the percentage of body weight gain, but an increase in the hepatosomatic index. In addition , the results illustrated an increase in the liver malondialdehyde (MDA) contents and hydrogen peroxide levels (H2O2) accompanied by significant decrease in reduced glutathione (GSH) content and superoxide dismutase (SOD) and glutathione-S-transferase (GST) activities.The results, also reported significant decrease in serum total proteins, total albumin , globulin and liver total protein but serum total bilirubin was significantly elevated in the DMBA intoxicated group. Furthermore, aspartate aminotransaminase (ASAT), alanine aminotransaminase (ALAT) , γ-glutamyltransferase (GGT) and alkaline phosphatase (ALP) activities were significantly increased in serum but significantly decreased in the liver. On the other hand, intake of hops, rosemary and cat's claw minimize the disturbances observed in most of the tested parameter's resulted from DMBA administration and improve the liver functions mostly in the following order, rosemary ˃ hops ˃ cat's claw. Conclusion: it can be concluded that intake of such herbs (hops , rosemary, cat's claw)may be effective in reducing DMBA toxicity.

Catʼs Claw Oxindole Alkaloid Isomerization Induced by Cell Incubation and Cytotoxic Activity against T24 and RT4 Human Bladder Cancer Cell Lines

The antitumor activity of Uncaria tomentosa, a native vine from the Amazonian rainforest, has been ascribed to pentacyclic oxindole alkaloids occurring in its bark. Former studies have shown that this activity, as well as its intensity, depends on whether cat's claw alkaloids occur as original compounds or isomerized derivatives. This work addresses this aspect, using T24 and RT4 human bladder cancer cell lines for that purpose. Bark samples were extracted by dynamic maceration, prepurified with cross-linked polyvinylpyrrolidone and properly fractioned by an ion exchange process to obtain an oxindole alkaloid purified fraction. Alkaloid isomerization was induced by heating it under reflux at 85 °C. Samples collected after 5, 15, and 45 min of heating were analyzed by HPLC-PDA, freeze-dried at once, and separately assayed using the non-isomerized purified fraction for comparison purposes. The latter showed significant and dose-dependent cytotoxic activity against both T24 and RT4 cancer cell lines (IC50: 164.13 and 137.23 µg/mL, respectively). However, results for both cell lines were equivalent to those observed for isomerized samples (p > 0.05). The alkaloid isomerization induced by the incubation conditions (buffered medium pH 7.4 and temperature 37 °C) helps to explain the similar results obtained from non-isomerized and isomerized samples. Mitraphylline, speciophylline, uncarine F, and, to a lesser degree, pteropodine were more susceptible to isomerization under the incubation conditions. Thus, the alkaloid profile of all fractions and their cytotoxic activities against T24 and RT4 human bladder cancer cell lines are determined to a large extent by the incubation conditions.

Anti-inflammatory and anti-tumour effects of two species of Cat's Claw (Uncaria)

Anti-inflammatory and anti-tumour effects of two species of Cat's Claw (Uncaria)

Mechanisms of Herb-Induced Nephrotoxicity

Herbal therapies gained much popularity among the general public, but compared to therapies approved by official authorities, toxicological studies are frequently not available for them. Hence, there may be inherent risks and the kidneys may be especially vulnerable to toxic effects. Herbs may induce nephrotoxicity by induction of apoptosis. High oxalate contents in Star fruit (Averrhoa carambola L.) may induce acute nephropathy. Triptolide from Thunder God Vine (Triperygium wilfordii Hook) is a diterpenoid epoxide with induces reactive oxygen species and nephrotubular apoptosis. Cranberry juice is discussed as promoter of kidney stone formation (nephrolithiasis). Abuse of guaifenesin from Roughbark (Guaicum officinale L.) increases stone formation. Aristolochia acids from Aristolochia fangchi Y.C.Wu ex L.D. Chow & S.M. Hwang causes the well-known aristolochic acid nephropathy and carcinogenesis by DNA adduct formation. Carboxyatractyloside from Impila (Callilepsis laureola DC.) inhibits mitochondrial ATP synthesis. Acute allergic interstitial nephritis was diagnosed after intake of Peruvian Cat's claw (Uncaria tomentosa Willd. DC.). Whether or not Willow Bark (Salix alba L.) induces analgesic nephropathwy is a matter of discussion. Other herbal therapies are considered to affect the rennin-angiotensisn-aldosterone (RAA) system Ephedra sinica Stapf with its ingredient ephedrine. Devil's Claw (Harpagophytum procumbens DC. Ex Meisn.) and licorice (Glycyrrhiza glabra L.) may inhibit major renal transport processes needed for filtration, secretion, and absorption. Strategies to minimize nephrotoxicity include (1) quality control and standardization of herbal products, (2) research on the molecular modes of action to better understand pathophysiological mechanisms of herbal products as well as (3) clinical trials to demonstrate efficacy and safety.