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BACKGROUND: Adjuvant aromatase inhibitors (AI) improve survival compared to tamoxifen in postmenopausal women with hormone receptor-positive stage I to III breast cancer. In approximately half of these women, AI are associated with aromatase inhibitor-induced musculoskeletal symptoms (AIMSS), often described as symmetrical pain and soreness in the joints, musculoskeletal pain and joint stiffness. AIMSS may have significant and prolonged impact on women's quality of life. AIMSS reduces adherence to AI therapy in up to a half of women, potentially compromising breast cancer outcomes. Differing systemic therapies have been investigated for the prevention and treatment of AIMSS, but the effectiveness of these therapies remains unclear. OBJECTIVES: To assess the effects of systemic therapies on the prevention or management of AIMSS in women with stage I to III hormone receptor-positive breast cancer. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, WHO International Clinical Trials Registry Platform (ICTRP) and Clinicaltrials.gov registries to September 2020 and the Cochrane Breast Cancer Group (CBCG) Specialised Register to March 2021. SELECTION CRITERIA: We included all randomised controlled trials that compared systemic therapies to a comparator arm. Systemic therapy interventions included all pharmacological therapies, dietary supplements, and complementary and alternative medicines (CAM). All comparator arms were allowed including placebo or standard of care (or both) with analgesia alone. Published and non-peer-reviewed studies were eligible. DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data, and assessed risk of bias and certainty of the evidence using the GRADE approach. Outcomes assessed were pain, stiffness, grip strength, safety data, discontinuation of AI, health-related quality of life (HRQoL), breast cancer-specific quality of life (BCS-QoL), incidence of AIMSS, breast cancer-specific survival (BCSS) and overall survival (OS). For continuous outcomes, we used vote-counting by reporting how many studies reported a clinically significant benefit within the confidence intervals (CI) of the mean difference

Samento (extract from Uncaria tomentosa) and Banderol (extract from Otoba parvifolia) have been demonstrated to have anti-inflammatory and antimicrobial properties, e.g., against different morphological forms of Borrelia burgdorferi. However, there is hardly any data on the pharmacological safety of these two herbal medicines. This in vitro study aimed at scrutinizing their possible characteristics as perpetrators in pharmacokinetic herbal⁻drug interactions. Inhibition of cytochrome P450 enzymes (CYPs) was quantified by commercial kits and inhibition of drug transporters by use of fluorescent probe substrates. Induction was quantified by real-time RT-PCR and activation of pregnane x receptor (PXR) and aryl hydrocarbon receptor (AhR) by reporter gene assays. Organic anion transporting polypeptide 1B1 (OATP1B1) (IC50 = 0.49 ± 0.28%) and OATP1B3 (IC50 = 0.65 ± 0.29%) were potently inhibited by Banderol, but only weakly by Samento. CYP3A4 was inhibited about 40% at a Samento concentration of 1%. Samento significantly induced mRNA expression of CYP2J2, UGT1A3, UGT1A9, ABCB1, and SLCO1B1 and strongly activated PXR, but hardly AhR. In conclusion, the perpetrator profiles of Samento and Banderol for herb⁻drug interactions completely differ. Clinical studies are strongly recommended to clarify whether the effects observed in vitro are of clinical relevance.

CONTEXT: Uncaria tomentosa D.C. (Rubiaceae) has several biological activities, including activity against resistant Candida strains. The synergistic interaction with terbinafine or fluconazole can be an important alternative to overcome this resistance. OBJECTIVES: The potential synergy between a water insoluble fraction (WIF) from Uncaria tomentosa bark and the antifungals terbinafine (TRB) and fluconazole (FLZ) against non-Candida albicans resistant strains was investigated. MATERIALS AND METHODS: TRB and FLZ, alone and combined with WIF, were tested by the checkerboard procedure using the micro-dilution technique against seven isolates of Candida glabrata and C. krusei. The molecular interactions occurring outside the cell wall were evaluated by scanning electron microscopy, Fourier transform infrared (FT-IR) and differential scanning calorimetry (DSC) analysis. RESULTS: The checkerboard inhibitory assay demonstrated synergy for WIF:TRB and WIF:FLZ combinations, respectively. The best synergistic cell damage was demonstrated unequivocally for the associations of WIF and TRB (1.95:4.0 μg/mL) and WIF and FLZ (1.95:8.0 μg/mL). The comparison of the FT-IR spectra of the antifungal alone, and in combination with WIF, allows recognizing clear differences in 3000, 1600, 1400, and 700-800 cm-1 bands. Additionally, modifications on TRB and FLZ thermograms were clearly noticed after their combination with WIF. CONCLUSIONS: DSC and infrared analysis demonstrated intermolecular interactions between WIF and either TRB or FLZ. Hence, quite likely the synergistic effect is related to interaction events occurring outside the cell wall between antifungal and cat's claw proanthocyanidins. A direct action on the cell wall is suggested, without connection with the ABC efflux pump mechanism.

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.

PURPOSE: In recent years, a number of natural medicines have been reported to have inductive or inhibitive effects on the activity of drug metabolizing enzymes, upon co-administration with prescribed medicines. However, information regarding natural medicine-drug interactions that influence drug metabolism is limited owing to the lack of efficient screening method for such interactions. Therefore, to understand whether P450 activity is affected by natural medicine in small intestines, we have established frozen recombinant P450-expressing cells infected with human CYP3A4 expressing adenovirus (Ad-CYP3A4) to evaluate the effect of natural medicines on CYP3A4 activity. METHODS: Ad-CYP3A4 cells were created by infecting HepG2 cells with Ad-CYP3A4 at 10 multiplicity of infection (MOI) and these cells were stored using cryopreservation medium (fAd-CYP3A4 cells) to obtain long-term consistent data and stable supplies of cells expressing a constant level of CYP3A4 activity. RESULTS: The CYP3A4 activity in fAd-CYP3A4 cells remained unaffected at the end of each frozen period (0, 1, 2, and 6 months). Inhibitory effect on CYP3A4 activity by typical inhibitors (ketoconazole, hyperforin) and natural medicines (Cat's Claw, Devil's Claw, Feverfew, Peppermint Oil, Red Clover, and Siberian Eleuthero) were evaluated. The inhibitors had nearly equal IC50 values in fAd-CYP3A4 cells, Ad-CYP3A4 cells and recombinant CYP3A4 microsomes. Cat's Claw, Peppermint Oil and Siberian Eleuthero inhibited CYP3A4 activity more potently than 0.1 μM ketoconazole in fAd-CYP3A4 cells. CONCLUSIONS: In the present study, we have successfully developed a highly reproducible system to evaluate CYP3A4 inhibition in small intestines by natural medicines.

The use of traditional/complementary/alternate medicines (TCAMs) in HIV/AIDS patients who reside in Southern Africa is quite common. Those who use TCAMs in addition to antiretroviral (ARV) treatment may be at risk of experiencing clinically significant pharmacokinetic (PK) interactions, particularly between the TCAMs and the protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Mechanisms of PK interactions include alterations to the normal functioning of drug efflux transporters, such as P-gp and/or CYP isoenzymes, such a CYP3A4 that mediate the absorption and elimination of drugs in the small intestine and liver. Specific mechanisms include inhibition and activation of these proteins and induction via the pregnane X receptor (PXR). Several clinical studies and case reports involving ARV-herb PK interactions have been reported. St John's Wort, Garlic and Cat's Claw exhibited potentially significant interactions, each with a PI or NNRTI. The potential for these herbs to induce PK interactions with drugs was first identified in reports of in vitro studies. Other in vitro studies have shown that several African traditional medicinal (ATM) plants and extracts may also demonstrate PK interactions with ARVs, through effects on CYP3A4, P-gp and PXR. The most complex effects were exhibited by Hypoxis hemerocallidea, Sutherlandia frutescens, Cyphostemma hildebrandtii, Acacia nilotica, Agauria salicifolia and Elaeodendron buchananii. Despite a high incidence of HIV/AIDs in the African region, only one clinical study, between efavirenz and Hypoxis hemerocallidea has been conducted. However, several issues/concerns still remain to be addressed and thus more studies on ATMs are warranted in order for more meaningful data to be generated and the true potential for such interactions to be determined.

The safety of natural drugs is defined by their side effects and toxicity as well as any interactions that may occur if taken together with other drugs. In particular, it is essential to identify synergies, antagonisms and other types of interference with other drugs so that the correct choice can be made from the range of phytomedicines available. The aim of this work was to investigate changes in the pharmacological effect of diazepam (2 mg/kg) on the CNS when administered together with a medicinal plant: Eucalyptus globulus Labill. (eucalyptus 6 mg/kg and 3.25 mg/kg) or Uncaria tomentosa (Willd. ex Roem. & Schult). DC. (cat's claw, 7.14 mg/kg and 3.54 mg/kg). Various different psychopharmacological effects were evaluated through assessing exploratory behavior, muscle relaxation and spontaneous motor activity. Both phytodrugs interacted with the benzodiazepine. Eucalyptus had an inhibitory effect at both doses and could be useful at the highest dose in cases where the desired effect of the depressant is moderate anxiolytic activity without marked muscle relaxation. Cat's claw, at both doses, enhanced the action of diazepam on spontaneous motor activity and, at the lowest dose, exploratory ability. These herbal drugs could be useful for their antiinflammatory activity in musculoskeletal pathologies treated with benzodiazepines.

47. Am J Health Syst Pharm. 2009 Jun 1;66(11):992-5. doi: 10.2146/ajhp080443. Pharmacology and therapeutic uses of cat's claw. Erowele GI(1), Kalejaiye AO. Author information: (1)Formulary Management and Pharmacoeconomics, Harris County Hospital District, Ben Taub General Hospital, 1504 Taub Loop, Houston, TX 77030, USA. [email protected] DOI: 10.2146/ajhp080443 PMID: 19451609 [Indexed for MEDLINE]

48. Eur J Clin Pharmacol. 2008 Dec;64(12):1235-6. doi: 10.1007/s00228-008-0551-1. Epub 2008 Aug 20. Interaction between cat's claw and protease inhibitors atazanavir, ritonavir and saquinavir. López Galera RM, Ribera Pascuet E, Esteban Mur JI, Montoro Ronsano JB, Juárez Giménez JC.

Combining nutritional supplements to achieve synergistic benefit is a common practice in the nutraceutical industry. However, establishing added health benefit from a combination of natural ingredients is often assumed, untested and without regard to the principle of metabolic competition between the active components. Here, we report on the combination of a cat's claw water extract (C-Med-100, carboxy alkyl esters = active ingredients) + medicinal mushroom extracts (Cordyceps sinensis, Grifola blazei, Grifolafrondosa, Trametes versicolor and Ganoderma lucidum, polysaccharides = active ingredients) + nicotinamide + zinc into a formulation designed to optimize different modes of immunostimulatory action, and yet that would avoid metabolic antioxidant competition yielding less than expected efficacious effects. Isobole curve analyses of these two active classes of ingredients determined by growth inhibition of HL-60 human leukemic cells in vitro confirmed they were indeed synergistic when in combination, and not metabolically competitive. Furthermore, an in vivo study showed significant health benefit for 14 subjects treated for 4 weeks with the unique C-Med-100/mushroom extract formulation in that they had reduced pain, reduced fatigue, weight loss and a reduced presence of DNA damage in peripheral blood assessed by (8-OH) guanine DNA adducts and elevation in serum protein thiols. Because this broad-based panel of clinical parameters indicating clinical efficacy has never been demonstrated before for either of the active ingredients evaluated alone in humans, these data were taken as strong evidence that the combination of C-Med-100 + mushroom extracts + nicotinamide + zinc gave additive or synergistic effects to health benefit, and thus supported no efficacious limits from metabolic competition regarding this particular formulation.

Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and 13 related pure plant compounds have been analyzed for their in vitro cytochrome P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate assay. Roughly 75% of the commercial products and 50% of the pure compounds showed significant inhibition of CYP3A4 metabolite formation. For each herbal product and pure compound exhibiting dose-dependency, the inhibition values were used to generate median inhibitory concentration (IC50) curves using linear regression. Among the commercial extracts, Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort), and Uncaria tomentosa (cat's claw) had the lowest IC50 values at < 1% full strength, followed by Echinacea angustifolia roots, Trifolium pratense (wild cherry), Matricaria chamomilla (chamomile), and Glycyrrhiza glabra (licorice), which had IC50 values ranging from 1%-2% of full strength. Dillapiol, hypericin, and naringenin had the lowest IC50 values among the pure plant compounds at < 0.5 mM; dillapiol was the most potent inhibitor at 23.3 times the concentration of the positive CYP3A4 inhibitor ketoconazole. Utilizing high-throughput screening methodologies for assessing CYP3A4 inhibition by natural products has important implications for predicting the likelihood of potential herbal-drug interactions, as well as determining candidates for further in-depth analyses.

Cancer-related fatigue (CRF) is one of the most debilitating symptoms experienced by cancer patients, with a multifactorial etiology involving inflammatory, metabolic, neuroendocrine, and psychological mechanisms. As pharmacological treatments for CRF remain limited and often ineffective, interest has grown in complementary approaches, including the use of Amazonian and related plant extracts. Plant extracts contain various bioactive compounds with multiple pharmacological activities that may be beneficial in addressing complex multifactorial symptoms such as CRF. PURPOSE: This narrative review evaluates the clinical and mechanistic evidence surrounding the use of two Amazonian plants-Paullinia cupana (guaraná) and Uncaria tomentosa (cat's claw)-and one Asian-origin plant naturalized in the Brazilian Amazon-Zingiber zerumbet (bitter ginger)-for the management of CRF. MAJOR FINDINGS: We discuss their phytochemical profiles, proposed biological effects, and the findings of preliminary clinical studies. A notable limitation of the available evidence is that ten of the twelve clinical studies reviewed originate from the author's home institution (Faculdade de Medicina da Fundação ABC), raising important questions about generalizability that future multicenter trials should address. Although preliminary results suggest potential benefits in CRF symptom control and quality of life, methodological limitations and heterogeneity across studies warrant caution. Importantly, guaraná was associated with worsening outcomes in patients with head and neck cancer undergoing concurrent chemoradiotherapy, underscoring that treatment-type-specific safety must be carefully considered before clinical use. CONCLUSIONS: Further well-powered, placebo-controlled,

Type 2 diabetes (T2D) is a metabolic syndrome frequently associated with obesity and endoplasmic reticulum stress-mediated inflammation, which can trigger the unfolded protein response (UPR), impair insulin signaling, and promote apoptosis. To identify potential natural therapeutic candidates, this study investigated the mechanisms of action of 14 compounds from Uncaria tomentosa (UT), a medicinal plant from the Amazon rainforest, using in silico modeling. The study focused on the UPR, TRAF2/JNK pro-inflammatory signaling pathway, and insulin signaling pathways, which play key roles in T2D. Some of the UT compounds were docked against several human proteins involved in these pathways, and molecular dynamics simulations confirmed stable interactions between the target proteins (PERK, TRAF2, JNK, TNF-α, IRS-1, PI3K, AKT, GSK3β, and PPARγ) and four of the UT compounds, 5-Carboxystrictosidine, Cinchonain, Epicatechin and Mitraphylline. Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties analyses were conducted to predict the four compounds, revealing suitable pharmacokinetic properties. These findings suggest that specific UT compounds may be used in experimental tests to whether investigate their therapeutic potential in managing T2D by modulating signaling pathways related to the conditions UPR, inflammation, and insulin resistanc

Quinovic acid is a key constituent of cat's claw (Uncaria tomentosa) extract and exhibits antioxidant and anti-inflammatory activities. In this study, we investigated the potential of quinovic acid to enhance natural killer (NK) cell activity by using the KHYG-1 cell line. Our data indicated that quinovic acid increased the expression levels of cytolytic molecules, including perforin, granzymes A and B, Fas ligand, and granulysin, and induced the phosphorylation of the transcription factors CREB and STAT4, thereby enhancing cytotoxic activity against K562 cells. Furthermore, when KHYG-1 cells were cocultured with K562 cells in the presence of quinovic acid, we observed an increase in the expression of t-Bid, cleaved caspases 3, 8, and 9, and PARP, promoting apoptosis in K562 cells. Quinovic acid also reduced the expression of SET, Ape1, and HMGB2, effectively inhibiting the DNA repair mechanism in target cells. Similar results were observed in other cancer cell lines. In addition, quinovic acid induced interferon-gamma secretion by upregulating the Ras/MAPK and PI3K/AKT/mTOR

Uncaria tomentosa (Ut) is a Rubiaceae widely used in Peru's traditional medicine. It is mainly known by the vernacular name of Cat's claw due to its morphological aspects and is found in tropical low mountain forests of Central and South America. A decoction of Ut bark, root and leaves is used traditionally for different health problems, including arthritis, weakness, viral infections, skin disorders, abscesses, allergies, asthma, cancer, fevers, gastric ulcers, haemorrhages, inflammations, menstrual irregularity, rheumatism, urinary tract inflammation and wounds, among others, which gave rise to scientific and commercial interest. The present paper reviews research progress relating to the ethnobotany, phytochemistry and pharmacology of Ut, and some promising research routes are also discussed. We highlight the centrality of its different biological activities, such as antioxidant, anti-inflammatory, antiproliferative, antiviral, and antinociceptive, among others. Recently, studies of the health effects of this plant suggest that novel nutraceuticals can be obtained from it and applied as a preventive or prophylaxis strategy before the start of conventional drug therapy, especially for patients who are not prone to conventional pharmacological approaches to diseases. The present work emphasizes the current pharmacolo

BACKGROUND: Uncaria tomentosa (cat's claw) is a medicinal plant with documented immunomodulatory and anti-inflammatory properties. Recent studies suggest potential anticancer effects, but evidence remains fragmented. OBJECTIVE: This systematic review aimed to assess the cytotoxic effects of different U. tomentosa extracts or fractions on normal and cancer cells, summarizing in vitro studies. METHODS: A systematic search was conducted in PubMed, Embase, and Scielo up to January 2025, following PRISMA guidelines. Inclusion criteria comprised in vitro studies evaluating U. tomentosa extracts or fractions on normal and cancer cells, reporting IC50 values or equivalent measures. Data on plant part, extraction method, and chemical composition were collected. Risk of bias was assessed using the modified CAMARADES checklist. RESULTS: Thirteen studies met the eligibility criteria. U. tomentosa extracts exhibited selective cytotoxicity in some cancer cell lines. The most promising findings were observed for crude aqueous bark extracts (72 h incubation) against squamous cell carcinoma and pentacyclic oxindole alkaloid (POA)-rich extracts against prostate cancer and leukemia. In contrast, tetracyclic oxindole alkaloid (TOA)- and proanthocyanidin (PAC)-rich fractions showed limited cytotoxicity. Most extracts were non-toxic to normal cells, except for the crude aqueous bark extract, which exhibited cytotoxicity in keratinocytes. CONCLUSION: U. tomentosa has potential as a source of selective anticancer agents, particularly thro

ETHNOPHARMACOLOGICAL RELEVANCE: Medical Uncariae Ramulus Cum Uncis consists of Uncaria rhynchophylla (Miq.) Miq. ex Havil, Uncaria macrophylla Wall, Uncaria sinensis (Oliv.) Havil, Uncaria hirsuta Havil, and Uncaria sessilifructus Roxb, which belongs to the species widely used in the genus Uncaria. These species resource widely distributed in China and abroad, and the hook-bearing stem is the primary constituent enrichment site. There are many different forms and architectures of chemicals, depending on the extraction site. Traditional remedies employing URCU had been used widely in antiquity and were first compiled in renowned ancient masterpiece 'Mingyi Bielu ()' written by Hongjing Tao. In modern pharmacological studies, both the total extracts and the phytoconstituents isolated from URCU have been shown to have neuroprotective, antioxidant, anti-inflammatory, anticancer, antibacterial, and autophagy-enhancer properties. AIM OF THE STUDY: This review concentrates on the traditional uses, phytochemistry, pharmacology, toxicology, and nanomaterials studies of URCU, with a perspective to assist with further research and advance. MATERIAL AND METHODS: The Chinese and English literature studies of this review are based on these database searches including Science Direct, CNKI, Wiley online library, Spring Link, Web of Science, PubMed

Uncaria tomentosa is a medicinal plant native to Peru that has been traditionally used in the treatment of various inflammatory disorders. In this study, the effectiveness of U. tomentosa as an anti-cancer agent was assessed using the growth and survival of B16-BL6 mouse melanoma cells. B16-BL6 cell cultures treated with both ethanol and phosphate-buffered saline (PBS) extracts of U. tomentosa displayed up to 80% lower levels of growth and increased apoptosis compared to vehicle controls. Treatment with ethanolic extracts of Uncaria tomentosa were much more effective than treatment with aqueous extracts. U. tomentosa was also shown to inhibit B16-BL6 cell growth in C57/bl mice in vivo. Mice injected with both the ethanolic and aqueous extracts of U. tomentosa showed a 59 ± 13% decrease in B16-BL6 tumour weight and a 40 ± 9% decrease in tumour size. Histochemical analysis of the B16-BL6 tumours showed a strong reduction in the Ki-67 cell proliferation marker in U. tomentosa-treated mice and a small, but insignificant increase in terminal transferase dUTP nick labelling (TUNEL) staining. Furthermore, U. tomentosa extracts reduced angiogenic markers and reduced the infiltration of T cells into the tumours. Collectively, the results in this study concluded that U. tomentosa has potent anti-cancer activity that significantly inhibited cancer cells in vitro and in vivo.

Breast cancer is currently the most common cancer and the leading cause of cancer death among women worldwide. Advanced breast cancer is prone to metastasis, and there is currently no drug to cure metastatic breast cancer. The purinergic ligand-gated ion channel 7 receptor is an ATP-gated nonselective cation channel receptor and is involved in signal transduction, growth regulation, cytokine secretion, and tumor cell development. Recent studies have shown that upregulation of the P2X7 receptor in breast cancer can mediate AKT signaling pathways, Ca2 þ-activated SK3 potassium channels, and EMT and regulate the secretion of small extracellular vesicles to promote breast cancer invasion and migration, which are affected by factors such as hypoxia and ATP. In addition, studies have shown that microRNAs can bind to the 3' untranslated region of the P2X7 receptor, which affects the occurrence and development of breast cancer by upregulating and downregulating P2X7 receptor expression. Studies have shown that new P2X7 receptor inhibitors, such as emodin and Uncaria tomentosa, can inhibit P2X7 receptor-mediated breast cancer invasion and are expected to be used clinically. This article reviews the research progress on the relationship between the P2X7 receptor and breast cancer to provide new ideas and a basis for clinical diagnosis and treatment.

Uncaria tomentosa (UT) extracts have been shown to have promising anti-tumor activity. We hypothesized that its incorporation into nanostructured systems could improve the anticancer properties. Here, poly-e-caprolactone (PCL) and poly-d,l-lactide-co-glycolide (PLGA) were employed to generate nanoparticles loaded with UT extract in a single emulsion solvent evaporation method. The nanoparticles were characterized by particle size, zeta potential, morphology and entrapment efficiency along with stability and release profiles. The nanoparticles presented entrapment efficiencies above 60% and a mean diameter below 300nm. UT-PCL nanoparticles presented higher entrapment efficiency and mean particle size as well as a slow release rate. The UT-PLGA nanoparticles showed higher drug loading. Two prostate cancer cell-lines, LNCaP and DU145 that were derived from metastatic sites, served as model systems to assess cytotoxicity and anti-cancer activity. In vitro, both formulations reduced the viability of DU145 and LNCaP cells. Yet, the UT-PLGA nanoparticles showed higher cytotoxicity towards DU145 cells while the UTPCL against LNCaP cells. The results confirm that the incorporation of UT into nanoparticles could enhance its anti-cancer activities

BACKGROUND: The number of people with cancer using complementary and alternative medicine (CAM) is increasing. However, CAM may have interactions with conventional cancer therapies. In addition, alternative medicine procedures may result in significant health risks. Because of the Internet, regional CAM methods easily spread globally. This study aims at evaluating CAM procedures offered on Spanish-speaking South American websites and assessing the quality of these websites. METHODS: An Internet search was carried out in nine Spanish-speaking countries in South America. Websites were analysed using a standardized tool. RESULTS: In total, 85 websites, with a wide range of 158 different CAM procedures were evaluated. The vast majority of websites had poor content and formal quality. Overall, no website was rated as very good and only two websites could be rated as good. Among the most commonly mentioned South American methods were an Aloe- mixture called "Fray Romano", graviola, uncaria tomentosa (Cat's claw), the "Método HANSI" and components of the lapacho tree. CONCLUSIONS: There is an urgent need for quality-assured, easy-to-find sites with high quality for Spanish speaking persons in South America. Several of the methods have already spread to Europe as graviola or uncaria.

The inflammatory processes associated with several chronic illnesses like cardiovascular disease and cancer have been the focus of mechanistic studies of the pathogenicity of these diseases and of the use of different pharmacological and natural methods to prevent them. In this study we review the current evidence regarding the effectiveness of natural extracts from as-yet little-studied traditional botanical species in alleviating the inflammation process associated with several chronic diseases. Additionally, the intention is to expose the known pathways of action and the potential synergistic effects of the constituent compounds of the discussed extracts. It is noted that the here-studied extracts, which include black garlic rich in S-allylcystein, polyphenols from cat's claw (Uncaria tomentosa), devil's claw (Harpagophytum procumbens), camu-camu (Myrciaria dubia), and blackcurrant (Ribes nigrum), and citrus fruit extracts rich in hesperidin, have similar or greater effects than other, more extensively studied extracts such as tea and cocoa. The combined use of all of these extracts can give rise to synergetic effects with greater biological relevance at lower doses.

Uncaria tomentosa (U. tomentosa) or uña de gato, a species of vine of Rubiaceae family, was used from centuries in various medical conditions. Although there are no randomized controlled trials or published human outcome studies, some conditions reportedly improved by U. tomentosa include osteoarthritis, rheumatoid arthritis, prostatitis, viral illnesses and cancer (acting as a non-specific immunomodulantign agent) and it may also have potential as an immunomodulating adaptogen in cellular aging. The understanding of some specific mechanisms of molecular action leads to the demonstration of various anti-inflammatory, immunostimulating and protective effects. These results bring the strong hypothesis that U. tomentosa could be effective in the topical treatment of dermatological manifestation, namely rosacea.

Uncaria tomentosa (Willd.) DC. (Rubiacee), also known as uña de gato, is a plant that grows wild in the upper Amazon region of Peru and has been widely used in folk medicine to treat several health conditions including cancer. We have produced an aqueous extract from Uncaria tomentosa (UT-ex) and analyzed its effects on squamous carcinoma cells and immortalized HaCaT keratinocytes. Squamous cell carcinoma (SCC) is an uncontrolled growth of abnormal cells arising in the skin's squamous layer of epidermis. When detected at an early stage, SCCs are almost curable, however, if left untreated, they can penetrate the underlying tissue and become disfiguring. We have evaluated cell proliferation, apoptosis and the level of reactive oxygen species following UT-ex treatment. UT-ex affected cell cycle progression and reduced cell viability in a dose and time-dependent manner. From a mechanistic point of view, this delay in cell growth coincided wit

Uncaria tomentosa is a woody vine with a long history of use in traditional Peruvian medicine and nowadays supplements containing this vine as ingredient are available. Immunomodulating, anti-inflammatory and anticancer properties of Uncaria tomentosa have been suggested and attributed mainly to the presence of tetracyclic or pentacyclic oxindole alkaloids. However, the synergic action of different compounds occurring in extracts and modulation of redox processes may significantly influence the anticancer activity of Uncaria tomentosa. The aim of the present study was to investigate for the first time the cytotoxic effects of the tetracyclic alkaloids free aqueous extract (decoction) o

ETHOPHARMACOLOGICAL RELEVANCE: Uncaria 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 immu

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria 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 STUDY: To evaluate the influence of cat's claw chemotypes on genotoxicity and cytotoxicity against non malignant and malignant human cell line models. MATERIAL AND METHODS: Four 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 gen

BACKGROUND: Mitraphylline (MTP) is the major pentacyclic oxindolic alkaloid presented in Uncaria tomentosa. It has traditionally been used to treat disorders including arthritis, heart disease, cancer, and other inflammatory diseases. However, the specific role of MTP is still not clear, with more comprehensivestudies, our understanding of this ancient herbal medicine will continue growing. HYPOTHESIS/PURPOSE: Some studies provided its ability to inhibit proinflamatory cytokines, such as TNF-α, through NF-κB-dependent mechanism. TNF-α primes neutrophils and modulates phagocytic and oxidative burst activities in inflammatory processes. Since, neutrophils represent the most abundant pool of leukocytes in human blood and play a crucial role in inflammation, we aimed to determine the ability of MTP to modulate neutrophil activation and differentially regulate inflammatory-related cytokines. METHODS: To determine the mechanism of action of MTP, we investigated the effects on LPS-activated human primary neutrophils responses including activation surface markers by FACS and the expression of inflammatory cytokines, measured by real time PCR and ELISA. RESULTS: Treatment with MTP reduced the LPS-dependent activation effects. Activated neutrophils (CD16(+)CD62L(-)) diminished after MTP administratio

Objetives. This study aimed to research the in vitro immunomodulatory effects of an Uncaria tomentosa hydroalcoholic extract standardized (5.03%, pentacyclic oxindole alkaloids) (UT-POA) on the immunophenotype of dendritic cells (DC) subsets, Th1, Th2, Th17 and IL-12 cytokines from patients with stage II breast cancer (BCII) and healthy women (H). MATERIALS AND METHODS: Blood of 11 H and 7 BCII was obtained, PBMC were isolated and cultured for 2h with/without various concentrations of UT-POA and stimulated or not with LPS for 24h. PBMC were labeled with specific antibodies for DC and in the supernatant we measured Th1/Th2/Th17 cytokines, both by flow cytometry. Furthermore IL-12 was measured by ELISA. RESULTS: UT-POA did not alter DC or accessory molecules expression in BCII. However, H exhibited a decrease in the percentage of mDC (myeloid DC) and an increase in HLA-DR and CD86 expression at 1000 μg/mL. IL-12 secretion was modified only in the H group, increasing p70 subunit and decreasing p40 subunit. UT-POA increased Th1 (IFN-γ and IL-2), Th2 (IL-4) and Th17 (IL-17) secretion in both groups. CONCLUSIONS: UT-POA increased the production of cytokines related with anti-tumoral response at concentrations of 500-1000 μg/mL. This positive effect should be evaluated not only systemically but also in the tumor microenvironment in further studies. UT-POA may be a useful phytochemical in chemoprevention and in the alternative use in cancer therapies.

OBJECTIVES: To evaluate the immunomodulatory effect on lymphocyte subsets, dendritic cells (DC), Th1 / Th2 / Th17 and inflammatory cytokines on systemic level and/or in the tumor microenvironment of mice with or without melanoma. MATERIALS AND METHODS: Peripheral blood and/or primary tumors samples were obtained of mice with B16 melanoma treated or not with a hydroalcoholic extract of Uncaria tomentosa (UT) with 5.03% of pentacyclic oxindole alkaloids (UT-POA) obtained from the bark of the plant. All cell assays and cytokine measurements were performed by flow cytometry. RESULTS: UT-POA systemically increased CD4/CD8a relation while cell activation was inversely proportional; increased the proportion of DCm; induced a pro-inflammatory Th1 profile and reduced Th17 response. TNF-α and IL-17A positively and negatively correlated with CD4/CD8a relation. CONCLUSIONS: The increase of Th1 (TNF-α) may result in the increase of CD4 or M1 macrophage activation. Although UT-POA shows increased DCm, is not dose-dependent. Th17(IL-17A) decreased can support the function of CD8a lymphocytes. UT-POA shows better systemic immunomodulatory effects than intratumoral.

AC-11 is an aqueous extract of the botanical, Uncaria tomentosa, which has a variety of effects that enhance DNA repair and down regulate inflammation. AC-11 is essentially free of oxindole alkaloids (&lt; 0.05%, w/w) but contains more than 8% carboxy alkyl esters (CAEs) as their active ingredients. Three groups of 10 outbred SK-1 hairless or SK-II hairless strains of mice each were treated with AC-11 at 0.5%, 1.5%, and 3.0% in a non-irritating, dye-free, perfume-free, and fragrance-free vanishing cream vehicle. Ten mice used vehicle only and 10 were untreated. Each concentration of AC-11 and was applied daily to the backs of the mice prior to exposure to a 1,600-watt solar simulator used in this work (Solar Light Co. Philadelphia, PA) emitting (mainly Ultraviolet A (UVA) and B (UVB) radiation) duration of the experimental period with UVB wavelengths was filtered out with a 1.0 cm Schott WG 345 filter. AC-11 with a peak absorption at 200nm does act as a sun block. We tested for and focused on clinical appearance of mice and histological appearance of tumors in mice rather than metrics of radiation generated inflammation. Tumor progression scores were assigned as follows: 4+ = extensive tumor development; 3+ = early malignancies (raised palpable plaques)(early squamous cell cancers) 2+ = firm scaling, palpable keratosis (actinic keratoses); 1+ = light scaling with erythema. Following a total cumulative dose of 738 J/cm2, 85.7% all of the irradiated control animals, which did not receive AC-11 had precancerous actinic keratosis (AK)-type lesions (2+) (64.3% versus 42.9%) or early squamous cell carcinoma (SCC) (3+) (21.4% vs. 4.8%), in comparison with 47.7 % of AC-11-treated animals. There were no significant differences between the AC-11 groups. Three months after cessation of exposure to UVA radiation, the lesions in all but three of the 14 animals

OBJECTIVE: Cat's claw (Uncaria tomentosa) is a native Amazon plant that exhibits anti-inflammatory and antitumor properties. We wanted to assess its activity for symptom management of terminal cancer patients. METHODS: This prospective phase II study assessed the effects of a 100-mg dose of a dry extract of U. tomentosa three times per day in patients with advanced solid tumors who had no further therapeutic options and a life expectancy of at least 2 months. The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) and Functional Assessment of Chronic Illness Therapy - Fatigue questionnaires were used to assess the participants' quality of life, the Hospital Anxiety and Depression Scale questionnaire was used to assess anxiety and depression, and the Pittsburgh Sleep Quality Index was used to assess sleep quality. In addition, several biochemical and inflammatory parameters were analyzed. RESULTS: Fifty-one volunteers were recruited. Their median age was 64 (range, 33-85) years, and 47% of patients were female. More than 65% of patients had scores on the Karnofsky Performance Scale of 80% or less. Treatment improved the patients' overall quality of life (p=0.0411) and social functioning (p=0.0341), as assessed by the EORTC QLQ C-30, and reduced fatigue (p=0.0496) according to the Chalder Fatigue Questionnaire. None of the biochemical or inflammatory parameters assessed (interleukin-1 and -6, C-reactive protein, tumor necrosis factor-α, erythrocyte sedimentation rate, and α-1-acid glycoprotein) changed significantly. No tumor response was detected according to the Response Evaluation Criteria In Solid Tumors; however

22. Lancet Oncol. 2014 Nov;15(12):1299-300. doi: 10.1016/S1470-2045(14)71095-2. Epub 2014 Oct 26. Uncaria tomentosa, the cat's whiskers or claws? Froeling FE(1), Stebbing J(2). Author information: (1)Imperial College, London, UK. (2)Imperial College, London, UK. Electronic address: [email protected]. DOI: 10.1016/S1470-2045(14)71095-2 PMID: 25439687 [Indexed for MEDLINE]

Bladder cancer is the second most prevalent malignancy in the genitourinary tract and remains a therapeutic challenge. In the search for new treatments, researchers have attempted to find compounds with low toxicity. With this goal in mind, Uncaria tomentosa is noteworthy because the bark and root of this species are widely used in traditional medicine and in adjuvant therapy for the treatment of numerous diseases. The object

AIMS: Lactate dehydrogenase (LDH)-A is highly expressed in diverse human malignant tumors, parallel to aggressive metastatic disease, resistance to radiation/chemotherapy and clinically poor outcome. Although this enzyme constitutes a plausible target in treatment of advanced cancer, there are few known LDH-A inhibitors. STUDY DESIGN: In this work, we utilized a high-throughput enzyme micro-array format to screen and evaluate > 900 commonly used medicinal plant extracts (0.00001-.5 mg/ml) for capacity to inhibit activity of recombinant full length human LDHA; EC .1.1.1.27. METHODOLOGY: The protein sequence of purified enzyme was confirmed using 1D gel electrophoresis- MALDI-TOF-MS/MS, enzyme activity was validated by oxidation of NADH (500μM) and kinetic inhibition established in the presence of a known inhibitor (Oxalic Acid). RESULTS: Of the natural extracts tested, the lowest IC50s [<0.001 mg/ml] were obtained by: Chinese Gallnut (Melaphis chinensis gallnut), Bladderwrack (Fucus vesiculosus), Kelp (Laminaria Japonica) and Babul (Acacia Arabica). Forty-six additional herbs contained significant LDH-A inhibitory properties with IC50s [<0.07 mg/ml], some of which have common names of Arjun, Pipsissewa, Cinnamon, Pink Rose Buds/Petals, Wintergreen, Cat's Claw, Witch Hazel Root and Rhodiola Root. CONCLUSION: These findings reflect relative potency by rank of commonly used herbs and plants that contain human LDH-A inhibitory properties. Future research will be required to isolate chemical constituents within these plants responsible for LDH-A inhibition and investigate potential therapeutic application.