Article

Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content

Authors:
If you want to read the PDF, try requesting it from the authors.

Abstract

Cat's claw is an herbal medicine from the Amazon that is used widely to treat inflammatory disorders. The purpose of this study was to characterize the antioxidative and antiinflammatory properties of cat's claw, Uncaria tomentosa (UT) and Uncaria guianensis (UG). Alkaloids and flavanols were determined using reversed-phase HPLC; scavenging of 1,1-diphenyl-2-picrilhydrazyl (DPPH), hydroxyl radicals, and lipid peroxidation by spectrophotometry; and TNFalpha production by ELISA. Anti-inflammatory activity was assessed in vitro by inhibition of TNFalpha and nitrite production from RAW 264.7 cells exposed to LPS (50 ng/ml) and in vivo using the indomethacin-induced gastritis model. Apoptosis was assessed using the TUNEL technique and TNFalpha mRNA by in situ RT-PCR. In each of the antioxidant assays tested, UG was more potent than UT (P < 0.01). The total oxindole and pentacyclic alkaloid content of UT was 35-fold > UG. The IC50 value for inhibition of TNFalpha production was significantly (P < 0.01) higher for UT (14.1 ng/ml) vs UG (9.5 ng/ml), yet at concentrations that were considerable lower than that required for antioxidant activity. Non-alkaloid HPLC fractions from UT decreased LPS-induced TNFalpha and nitrite production in RAW 264.7 cells (P < 0.01) at a concentration range comparable to the parent botanical. Oral pretreatment for 3 d with UT protected against indomethacin-induced gastritis, and prevented TNFalpha mRNA expression and apoptosis. These results indicate that while both species of cat's claw provide effective antioxidant and anti-inflammatory activities, U. guianensis is more potent. In conclusion, the presence of oxindole or pentacyclic alkaloids did not influence the antioxidant and anti-inflammatory properties of cat's claw.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Uncaria tomentosa contains a large number of chemical components, including quinovic acid glycosides, triterpenes, and oxindole alkaloids [31,32], and differences in the methods used to produce extracts can result in different physiological effects. For example, an aqueous extract of Uncaria tomentosa, called C-Met-100 (which is rich in carboxyl alkyl esters but which contains relatively low levels of alkaloids [33]) was shown to be anti-inflammatory and immune system restorative [28,34,35], but did not provide significant anti-cancer activity in clinical trials [36]. Treatment with extracts enriched in quinovic acid glycosides were shown to decrease inflammatory side effects associated with anticancer drugs [29] and promote apoptosis in human bladder cancer cells [17]. ...
... HPLC analysis showed that the ethanol extract contained almost 10-fold higher levels of the diagnostic Uncaria alkaloids, uncarine D, mitraphylline, uncarine C, isomitraphyline, rhynophyline, and uncarine E, when compared to the PBS extracts. Others have shown that ethanol extracts are rich in pentacyclic oxindole alkaloids [5][6][7][8][9][10] and are important in mediating both anti-inflammatory and anti-cancer activities [12,17,29,33]. Some individual alkaloids, isolated from Uncaria extracts, such as mitroaphylline, have anti-proliferative [15] or pro-apoptotic effects on cancer cells [22] while Uncarine C (pteropodine) can inhibit DNA damage and scavenge free radicals in doxorubicin-treated mice [41]. ...
... However, an aqueous extract of Uncaria tomentosa, called C-Met-100 (which is rich in carboxyl alkyl esters but contains low levels of alkaloids) is antiinflammatory and an immune system restorative [35,42]. C-Med 100, is rich in quinovic acid and quinovic acid glycoconjugates, suggesting thar these molecules can inhibit inflammatory responses in vitro [34], promote lymphocyte survival in mice [35,42], and enhance DNA repair activity [36,43] independent of alkaloids [33]. The C-Med100 extract was able to inhibit cancer cell growth in vitro [44] and in mouse models of B16-BL6 metastasis [25] suggesting that these molecules might also have anti-cancer activity. ...
Article
Full-text available
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.
... ex Schult.) DC., commonly known as "unha-de-gato" (cat's claw), have been used in traditional medicine to treat inflammatory diseases [19,20]. ...
... The anti-inflammatory activities of Uncaria spp. have been previously demonstrated [19,20,33], thereby justifying the study of extracts and pure compounds derived from U. guianensis with the aim of improving the clinical manifestations of endometriosis. The chemical profiles of aqueous extracts of U. guianensis established herein were similar to those reported by Sandoval et al. [20] and characterized by low concentrations of pentacyclic oxindole alkaloids and high concentrations of phenolic compounds. ...
... have been previously demonstrated [19,20,33], thereby justifying the study of extracts and pure compounds derived from U. guianensis with the aim of improving the clinical manifestations of endometriosis. The chemical profiles of aqueous extracts of U. guianensis established herein were similar to those reported by Sandoval et al. [20] and characterized by low concentrations of pentacyclic oxindole alkaloids and high concentrations of phenolic compounds. ...
Article
Full-text available
There is increasing interest in the potential of natural compounds to treat diseases, such as endometriosis, a gynecological disorder that affects 10-15% of women of reproductive age, and it is related to severe pelvic pain and infertility. We have evaluated the in vitro effects of rutin and the aqueous bark, roots, and leaf extracts (ABE, ARE, and ALE, respectively) and isolated components of Uncaria guianensis on stromal cells from eutopic endometrium and lesions of patients with endometriosis. Two-and three-dimensional cultures were used to assess the cell death and production of reactive oxygen species (ROS), cytokines and growth factors of cells following exposure to these natural products. The applied treatments did not reduce cellular viability, but ROS production did increase. In addition, significant increases in the levels of interleukin (IL)-15, IL-17A, IL-4, IL-6, tumor necrosis factor-α, and vascular endothelium growth factor were observed when 2D-cells from endometrium of patients with endometriosis were treated with ABE, while exposure to ALE induced significant increases in epidermal growth factor in lesion cells.
... Different alkaloids, including 19-epi-ajmallicine, rauniticine, 14α-hydroxyraunitine, uncarine A, glabratine, deoxycordifoline, and flavonoids termed (+)-catechin, were detected in the barks and leaves U. glabrata (Arbain et al. 1992, Arbain et al. 1993, Arbain et al. 1998. Antioxidant activities of other Uncaria species such as U. tomentosa, U. guianensis, and U. gambir have been reported (Sandoval et al. 2002, Navarro-Hoyos et al. 2018, Apea-Bah et al. 2009). The level of toxicity and the potential to be used as novel anticancer agents and anti-Alzheimer`s disease have been also investigated (Azad et al. 2018, Xu et al. 2021. ...
... Furthermore, correlation between antioxidant activity and tannin content also was recorded in an earlier report (Bizuayehu et al. 2015). No correlation of the TAC type agreed with previous research by Sandoval et al. (2002), where the result of antioxidant activity from U. tomentosa and U. guianensis have not been correlated with their alkaloid content. ...
Article
Full-text available
Uncaria acida (red bajakah) and Uncaria glabrata (white bajakah) belong to the liana woody species. Both are naturally cultivated in Indonesia, particularly in Kalimantan (Borneo) island. This study, aims to investigate the extractive composition of U. acida and U. glabrata wood considering that extracts from different lianas usually are used as anticancer drugs (breast cancer). The phenolic, alkaloid, and saponin contents were measured by colorimetric and GC-MS methods, while the antioxidant, antifungal, and cytotoxicity were investigated using DPPH, Phanerodontia chrysosporium (white-rot), and brine shrimp lethality tests, respectively. The results showed that the total tannins, phenols, and saponins in U. acida were higher compared to U. glabrata, while the total flavonoids, alkaloids, polysaccharides, and antioxidant activity was lower. The GC-MS analysis indicated the presence of aromatic compounds, fatty acids, and triterpenoids in both species. High concentration of phenols, alkaloids, saponins, fatty acids, and steroids are known to provide support in terms of antioxidant, cytotoxicity, and antifungal activities.
... Moreover, incipient differences in the chemical composition of both species have been reported. Higher levels of pentacyclic (POA) and tetracyclic oxindole alkaloids (TOA) can be found in stem bark of U. tomentosa when compared to U. guianensis [6], specifications based only on oxindole alkaloids might not be enough to for the detection of adulteration with U. guianensis. ...
... Six genuine U. tomentosa stem bark samples (UT 1 -UT 6 ) and two U. guianensis stem bark samples (UG 1 -UG 2 ) collected in the Peruvian Amazon (November 2012) were certified by J.R. Campos De la Cruz (Museo de Historia Natural de la Universidad Nacional Mayor de San Marcos, Lima, Peru). The U. tomentosa samples were purposely selected to cover the three chemotypes recognized in this species [11], namely, POA with trans D/E ring junction (UT 1 and UT 2 ), TOA (UT 3 and UT 4 ) and POA with cis D/E ring junction (UT 5 and UT 6 ) ( Table 1). ...
... Cat's claw Pteridine, speciophylline, isomitraphylline, uncarine F, mitraphylline, isopteropodine Sandoval et al. (2002) present. Alkaloids have been described with many uses; nowadays they are used as chemotherapy agents, and also are being studied for their antidiabetic and neuroprotective capacity. ...
... Cat's claw Pteridine, speciophylline, isomitraphylline, uncarine F, mitraphylline, isopteropodine Sandoval et al. (2002) agents, that are considered as one of the most reliable classes of anti-neoplastic drugs in the treatment of breast cancer. As aforementioned, drug resistance is a persistent problem during chemotherapy treatment in cancer patients. ...
Chapter
Full-text available
Alkaloids are nitrogen-containing natural products found in bacteria, fungi, animals, and plants with complex and diverse structures. The widespread distribution of alkaloids along with their wide array of structures makes their classification often difficult. However, for their study, alkaloids can be classified depending on their chemical structure, biochemical origin, and/or natural origin. Alkaloids can be derived from several biosynthetic pathways, such as the shikimate pathway; the ornithine, lysine, and nicotinic acid pathway; the histidine and purine pathway; and the terpenoid and polyketide pathway. Traditionally, plant alkaloids have played a pivotal role in folk medicines since ancient times as purgatives, antitussives, sedatives, and treatments for a wide variety of ailments. Currently, several alkaloids have served as models for modern drugs, and there are several alkaloids used in pharmacology, such as codeine, brucine, morphine, ephedrine, and quinine. Herein, this work is a comprehensive revision from the Web of Knowledge and Scopus databases on the recent information (2010–2019) regarding plant-derived alkaloids, their structural classification and bioactive properties.
... Quinovic acid is a triterpene isolated from different plants [39][40][41]. Quinovic acids and other triterpenes are an important constituent of the cat's claw (Uncaria tomentosa) extract which is a medicinal plant and is widely used as a strong antioxidant with potent DPPH scavenging and antiinflammatory activity [42,43]. Likewise, the quinovic acid glycosides from the Guettarda platypoda and Uncaria tomentosa plants were among the initial studies to show anti-inflammatory activity in rats [44]. ...
... Previously, triterpenes or triterpenoids have been widely used as potent inducers of theKeap1/Nrf2 pathway as a therapeutic approach [90] in many neurodegenerative diseases including AD [91], Huntington's disease [92], Parkinson's disease [86], and multiple sclerosis (MS) [93]. Similarly, the quinovic acid in the cat's claw extract has been used as a strong antioxidant with potent DPPH scavenging and antiinflammatory activity [42,43]. ...
Article
Full-text available
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder typified by several neuropathological features including amyloid-beta (Aβ) plaque and neurofibrillary tangles (NFTs). Cholesterol retention and oxidative stress (OS) are the major contributors of elevated β- and γ-secretase activities, leading to excessive Aβ deposition, signifying the importance of altered cholesterol homeostasis and OS in the progression of Aβ-mediated neurodegeneration and cognitive deficit. However, the effect of Aβ on cholesterol metabolism is lesser-known. In this study, we evaluated the effect of quinovic acid (QA; 50 mg/kg body weight, i.p.) against the intracerebroventricular (i.c.v.) injection of Aβ (1-42)-induced cholesterol dyshomeostasis, oxidative stress, and neurodegeneration in the cortex and hippocampal brain regions of wild-type male C57BL/6J mice. Our results indicated that Aβ (1-42)-treated mice have increased Aβ oligomer formation along with increased β-secretase expression. The enhanced amyloidogenic pathway in Aβ (1-42)-treated mice intensified brain cholesterol accumulation due to increased expressions of p53 and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) enzyme. Importantly, we further confirmed the p53-mediated HMGCR axis activation by using pifithrin-α (PFT) in SH-SY5Y cells. Furthermore, the augmented brain cholesterol levels were also associated with increased OS. However, the QA administration to Aβ (1-42)-injected mice significantly ameliorated the Aβ burden, p53 expression, and cholesterol accumulation by deterring the oxidative stress through upregulating the Nrf2/HO-1 pathway. Moreover, the QA downregulated gliosis, neuroinflammatory mediators (p-NF-κB and IL-1β), and the expression of mitochondrial apoptotic markers (Bax, cleaved caspase-3, and cytochrome c). QA treatment also reversed the deregulated synaptic markers (PSD-95 and synaptophysin) and improved spatial learning and memory behaviors in the Aβ-treated mouse brains. These results suggest that Aβ (1-42) induces its acute detrimental effects on cognitive functions probably by increasing brain cholesterol levels through a possible activation of the p53/HMGCR axis. However, QA treatment reduces the cholesterol-induced oxidative stress, neuroinflammation, and neurodegeneration, leading to the restoration of cognitive deficit after Aβ (1-42) i.c.v. injection in mice. 1. Introduction Alzheimer’s disease (AD) is the major progressive neurodegenerative disorder associated with brain atrophy and dementia and is typified by various neuropathological features including the presence of extracellular neuritic plaques of amyloid-beta (Aβ) peptides and hyperphosphorylated tau in intraneuronal neurofibrillary tangles (NFTs) [1, 2]. There is a strong correlation between altered Aβ metabolism and increased p53 expression levels [3–6]. p53 is a tumor-suppressor protein involved in cell cycle control or apoptosis, and its role in cell death and neurodegeneration has been extensively discussed [7, 8]. p53 has diverse biological functions and is known to modulate several pathways [9], including cholesterol metabolism [10, 11], and regulate the activity of important enzymes of the mevalonate (MVA) pathway, including 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) to alter cholesterol metabolism [12]. The perturbation in cholesterol metabolism inside the body can be catastrophic to the brain and is manifested by progressive neuronal cell death [13]. Although most studies illuminated how cholesterol homeostasis affects the production and amyloid precursor protein (APP) processing in promoting AD pathology, very little is known about the influence of Aβ on altering the cellular cholesterol metabolism [14, 15]. Michikawa et al. have previously revealed that oligomeric Aβ in cultured astrocytes and neurons releases cholesterol and phospholipids [16]. Similarly, Aβ can increase synthesis and alter the distribution of free cholesterol in neurons [17]. The oligomeric Aβ (1-40) may also lose its neuroprotective activity [18] and modulates the synthesis and cellular cholesterol homeostasis in the rat’s primary cultured neurons [19]. The extracellular cholesterol is also known to reside in aggregated Aβ in transgenic (with Swedish Alzheimer mutation APP751) mice and neuritic plaques of AD patients [20]. However, the effect of Aβ (1-42) oligomers on cholesterol dyshomeostasis and metabolism especially in vivo and its concomitant detrimental effects on neurodegeneration are less well defined and may offer novel insights into mechanisms based on the amyloid cascade hypothesis. Oxidative stress (OS) plays an important role in the pathogenesis of many neurodegenerative diseases [21] and is considered to be an early event observed in AD disease progression [22, 23]. The cholesterol-mediated alterations deteriorate the critical antioxidant defense system by impairing mitochondrial GSH transport, reducing the cell susceptibility to different stimuli to reduce oxidative stress [24, 25]. The oxidized cholesterol products including oxysterols illustrate a fundamental role in AD progression by increasing oxidative stress linking hypercholesterolemia and altered cholesterol metabolism to neurodegenerative disease [14, 26]. The HMGCR (a key enzyme in the mevalonate pathway) competitive inhibitor statin has been shown in multiple studies in reducing AD pathology [27]. However, some actions of statins are assumed to be associated with the pleiotropic effect on OS, neuroinflammation, and brain oxygenation in particular [28, 29], instead of lowering cholesterol [30–32]. Cholesterol retention is also one of the major reasons for elevated β- and γ-secretase activities, leading to excessive Aβ deposition [33] that can further induce free radicals [34], along with different oxidative stress markers [35], and leads to the abnormal intermediation of the Keap1/Nrf2/ARE pathway [36–38]. Quinovic acid is a triterpene isolated from different plants [39–41]. Quinovic acids and other triterpenes are an important constituent of the cat’s claw (Uncaria tomentosa) extract which is a medicinal plant and is widely used as a strong antioxidant with potent DPPH scavenging and anti-inflammatory activity [42, 43]. Likewise, the quinovic acid glycosides from the Guettarda platypoda and Uncaria tomentosa plants were among the initial studies to show anti-inflammatory activity in rats [44]. Moreover, triterpenes possess potential activity against diabetes-induced β-cell damage that mostly is superseded by OS-mediated inflammation [45]. Previously, we have reported that quinovic acid and its glycoside derivatives have been shown to have strong inhibitory activity against dipeptidyl peptidase-4 (DPP-4) [41], which is an important enzyme involved in cleaving various neuropeptides and incretin hormones possessing anti-inflammatory activity [46]. Here, we have studied the proteotoxic effect of i.c.v. Aβ (1-42) oligomers on brain cholesterol upsurge associated with OS and its effect on neurodegeneration and behavioral deficits and its possible neuroprotection through antioxidant quinovic acid in reducing AD disease pathology in mice. Our results make evident that oligomeric Aβ (1-42) isoform has an acute effect on cholesterol dyshomeostasis and OS with interactive influence on neuronal loss and synaptic/memory dysfunction and that administering quinovic acid to the mice protects against Aβ-neurotoxicity; alleviates disease pathology by reducing cholesterol-mediated OS, glial activation, and neuroinflammation; and improves memory deficits in the (i.c.v.) β-amyloid mouse model. 2. Materials and Methods 2.1. Drug Preparation For in vivo intracerebroventricular (i.c.v.) administration, Aβ (1-42) peptide was prepared as formerly mentioned [47]. Briefly, the human Aβ (1-42) peptide (purchased from Sigma Chemicals Co.) was prepared in a sterile saline solution at a stock concentration of 1 mg/ml followed by aggregation via incubation at 37°C and administered at 5 μl/mice. For in vitro studies, the oligomeric Aβ (1-42) (AβO) was prepared as reported previously [48]. Concisely, the Aβ (1-42) peptide was dissolved in 100% hexafluoroisopropanol (HFIP). The HFIP was then evaporated under vacuum and reconstituted in dimethyl sulfoxide (DMSO) to produce 5 mM suspension. The 5 mM HFIP-treated Aβ (1-42) suspension was further diluted to 100 μM in F12 culture media (Gibco by Life Technologies, USA) lacking phenol red and incubated for 24 h at 5°C. The solution containing peptide was centrifuged at 14,000 rpm for 10 min at 4°C, and the supernatant containing AβO was collected. For cell treatment, AβO was used at a final concentration of 5 μM. The quinovic acid (QA) was isolated as previously reported [41] and was dissolved in a saline solution for in vivo administration and in DMSO for in vitro analysis. Pifithrin-α (Axon Medchem) was dissolved in DMSO and used at a concentration of 10 μM for in vitro analysis. 2.2. Cell Culture, MTT Assay, and Treatment Human neuroblastoma SH-SY5Y cells (purchased from Korean Cell Line Bank) were grown in MEM+F12 (1 : 1) supplemented with 1% penicillin-streptomycin and 10% fetal bovine serum. Cells were cultured in saturated humidified air containing 5% CO2 at 37°C. The experiments were commenced until cells grew up to 60-70% confluence. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was used to evaluate the levels of cell viability and dose optimization as performed previously [49]. SH-SY5Y cells were grown in a 96-well assay plate ( cells/well) in 100 ml/well of MEM+F12 (1 : 1) media augmented with 1% penicillin-streptomycin and 10% FBS. The cells were incubated in humidified air with 5% CO2 at 37°C, and the medium was changed at a regular interval. At 60-70% confluence media were changed, and the cells were either treated alone with different concentrations of quinovic acid (0, 5, 10, 30, 55, 70, 85, 100, and 115 μM) dissolved in DMSO or cotreated with AβO (5 μM) for dose optimization and incubated for 24 h at 37°C. The final concentration of DMSO was kept less than 0.25% in each well. Control culture wells either contained maintenance media or were augmented with 0.2% DMSO (vehicle control). After incubation, 10 μl of MTT (5 mg/ml in PBS)/well was added and incubated for 4 h. The blue formazan formed was solubilized by adding 100 μl of DMSO after media were removed and incubated for another 10-15 min. The absorbance intensity was measured at 550-570 nm using a microplate reader ApoTox-Glo™ (Promega, Madison, WI, USA). The experiments were performed in triplicate. For western blot analysis, SH-SY5Y cells were seeded in a 100 mm Petri dish. After 70% confluence, the cells were treated with the following: (a) AβO (5 μM) alone, (b) pretreated 60 min with pifithrin-α (10 μM) before exposure to AβO, (c) AβO cotreated with quinovic acid (85 μM), (d) treated with PFT, or (e) quinovic acid alone for 24 h. AβO concentration of 5 μM was used in all culture experiment. Control cells were only incubated with the pure medium. After 24 h of incubation, cells were collected in PBS by scraping and centrifuged at for 10 min at 4°C. The supernatant was removed, and PRO-PREP (a protein extraction solution) was added according to the manufacturer’s approved guidelines (iNtRON Biotechnology) followed by sonication and centrifuged at 4°C at 13,000 rpm for 30 min, and supernatants were collected to obtain cell lysates. The protein concentration in lysates was quantified using the Bio-Rad assay solution. 2.3. Experimental Subjects Male C57BL/6J wild-type mice were obtained from Samtako Bio Korea and were approximately 25-30 g and 8 weeks old at the start of experiments. The animals were randomly retained in groups of four in each cage and acclimatized for one week at room temperature in a fully controlled university animal facility (12 : 12 h light-dark cycle at ) with free access to water and chow. The animals were assigned to the following 3 different groups ( mice/group): saline-treated control, Aβ+saline, and Aβ+QA. All experiments in the current study followed the guidelines and principles of the Animal Ethics Committee (IACUC) (Approval ID: 125) from the Division of Life Sciences and Applied Life Sciences at Gyeongsang National University (GNU), South Korea. 2.4. Mouse Model and Drug Administration For Aβ (1-42) i.c.v. administration, the mice were anesthetized with a Rompun : Zoletil ratio of 0.5 ml/100 g body weight and were intracerebroventricular (i.c.v.) injected with aggregated Aβ (1-42) or vehicle control (saline) stereotaxically using a Hamilton microsyringe inserted 1 mm median-to-lateral, -0.2 mm from anterior-to-posterior, and -2.4 mm ventral-to-dorsal to the bregma. The Aβ (1-42) (total 5 μl/mice) was injected at the degree of 1 μl/5 min/mouse. The needle was left in place to avoid leakage or backflow for at least 3 min. The experiments were performed at a controlled temperature () to prevent hypothermia. Soon after the recovery period (24 h), the mice received quinovic acid at 50 mg/kg dose concentration or saline (0.1% normal) solution, administered intraperitoneally (i.p.) on alternative days for 3 weeks. Schematic representation of experimental procedure and drug administration is indicated in Figure 1.
... PTI-00703 cat's claw (the main ingredient in Percepta) demonstrated the most robust activity for Aβ fibril and tau tangle reduction/inhibition compared to all the other cat's claw extracts tested from different manufacturers. Cat's claw (Uncaria tomentosa) is a known and potent reducer of neuroinflammation due to its ability to reduce the inflammatory cytokines TNF-alpha and interleukin-1 [27][28][29][30][31] . This study demonstrated that one of the best dietary supplements targeting Aβ fibrils (major constituent of brain plaques) and tau paired helical/straight filament (major constituent in brian neurofibrillary tangles) was percepta. ...
... This confirmed that the formation of off-pathway soluble oligomers are not toxic to brain cells and are believed to be cleared/eliminated by microglia in the brain 5 . The reduction in neuroinflammation by cat's claw's is also probably caused by its known ability to markedly reduce the inflammatory cytokines interleukin-1 and TNF-α [27][28][29][30] . ...
Article
Full-text available
Memory loss is primarily caused by the accumulation of both brain plaques [(consisting of beta-amyloid protein (Aβ) 1–42)] and neurofibrillary tangles (consisting of paired helical and straight filaments containing tau protein). Neuroinflammation is the third key and important factor that leads to accelerated memory loss and eventual dementia. Brain plaques, tangles and inflammation is the trilogy mainly responsible for causing memory loss that has now been documented for over 20 years in the scientific literature. The present investigation used in vitro quantitative methods to directly compare the ability of major memory-support dietary supplements to reduce pre-formed Aβ 1–42 fibrils (21 supplements tested) and tau protein paired helical/straight filaments (13 supplements tested)—two of the three most important targets for memory loss. Additionally, 18 different manufacturers of cat’s claw (Uncaria tomentosa) were directly compared for their ability to inhibit/reduce Aβ 1–42 fibrils and/or tau paired helical/straight filaments based on recent findings that PTI-00703 cat’s claw is a specific and potent inhibitor/reducer of all three targets -brain plaques, tangles and inflammation (Snow et al. in Sci Rep 9:561, 2019). In the present investigation quantitative Thioflavin T fluorometry was used on a comparative weight-to-weight basis at increasing concentrations with ingredients tested from the actual capsules the consumer ingests. Major memory-support dietary supplements were directly compared for their ability to inhibit and disaggregate/reduce both Aβ 1–42 fibrils and/or tau paired helical/straight filaments. Dietary supplements touted to enhance memory comparatively tested included Prevagen, FOCUSfactor, PROCERA AVH, Alpha Brain, NAD⁺OVIM, BRAIN JUICE, Cebria, EXCELEROL, NOOCUBE, US Doctor’s Clinical Brain Power ADVANCED, healthycell pro, LUMONOL, Brain Awake, BRAIN ARMOR, brainMD (BRAIN & MEMORY POWER BOOST), Brain Support, Clarity (BRAIN HEALTH FORMULA), brainMD (NEUROVITE PLUS), neuriva (Original and Plus) and percepta. This is the first paper to actually comparatively test these memory-support supplements for their ability to reduce Aβ fibrils and tau protein tangles. Percepta (PTI-00703 cat’s claw and a specific oolong tea extract) was determined to be the most effective and potent memory support dietary supplement to disaggregate/disrupt Aβ 1–42 fibrils (range of 25–89%) and tau paired helical/straight filaments (range of 26–86%) at all 3–4 doses tested in comparison to other major memory-support dietary supplements tested. This was at least more than double (> 50%) for percepta reducing Aβ 1–42 fibrils and in comparison to the other 20 memory-support dietary supplements tested. The ranking order for memory-support supplement effects based on reducing Aβ 1–42 fibrils (Aβ 1–42: memory-support supplement at 1:0.1 weight-to-weight in a 3-day study) was percepta (69.6% reduction) >>> Alpha Brain (34.9% reduction) = US Doctor’s Clinical Brain Power ADVANCED (32.4%) = BRAIN JUICE (30.1%) = neuriva Plus (27%) = neuriva Original (27%) > NEUROVITE PLUS (22.9%) = NOOCUBE (19.9%) = EXCELEROL (17.3%) = healthycell pro (17.2%) > Prevagen (12.9%) > PROCERA AVH (6.5%) = FOCUSfactor (5.5%) > Cebria (0%) = Brain Awake (0%) = Brain Support (0%) = brainMD (BRAIN & MEMORY POWER BOOST) (0%) = NAD⁺OVIM (0%) = BRAIN ARMOR (0%) = LUMONOL (0%). The ranking order for memory support supplement effects on reducing tau paired helical/straight filaments (tau:memory supplement at 1:1 weight-to-weight at 3 days) was percepta (85.7% reduction) >>> neuriva Plus (57.9%) >> BRAIN JUICE (41.9%) = EXCELEROL (41.0%) = neuriva Original (38.4%) = US Doctor’s Clinical Brain Power ADVANCED (38.3%) = healthycell pro (37.6%) >> Alpha Brain (27.9%) >> NOOCUBE (17.6%) >> FOCUSfactor (8.7%) > Cebria (3.6%) = PROCERA AVH (0%) = Prevagen (0%). Congo red staining, Thioflavin S fluorescence, circular dichroism (CD) spectroscopy and electron microscopy confirmed the positive results observed with the supplement percepta. CD spectroscopy demonstrated that percepta caused a marked inhibition of beta-sheet secondary folding of tau protein into paired helical filaments. PTI-00703 cat’s claw (main ingredient in percepta) was also identified as the most potent cat’s claw bark powder (Uncaria tomentosa) to reduce and inhibit Aβ 1–42 fibrils and tau tangles in comparison to 17 other manufacturers of cat’s claw extracts. Although there are thousands of brain memory-support dietary supplements in the marketplace today, none of them have been directly compared and analyzed for their ability to reduce and/or inhibit two major targets of memory loss i.e. Aβ 1–42 fibrils and tau paired helical/straight filaments (major constituents of brain plaques and tangles). In our comparison studies, we show that percepta has the most potent ability to disaggregate/reduce Aβ 1–42 fibrils and tau protein paired helical/straight filaments as demonstrated by a variety of methods most likely due to the specific polyphenol content in PTI-00703 cat’s claw (i.e. polyphenols and proanthocyanidins) as we have previously shown (Snow et al. in Sci Rep 9:561, 2019). Memory-support dietary supplements tested that also contained polyphenols and/or cat’s claw in their product demonstrated some Aβ fibril and tau protein tangle reducing activity, but were much less effective than percepta. Percepta’s main ingredient, PTI-00703 cat’s claw, has previously been shown to reduce brain amyloid plaques and Aβ 1–42/40 insoluble/soluble levels in brain (in plaque-producing transgenic mice) with marked concurrent memory improvements (shown by Morris water maze testing) (Snow et al. in Sci Rep 9:561, 2019). The present investigation further confirms that percepta is one of the best dietary supplements that causes a marked reduction and inhibition of Aβ fibrils and tau tangle filaments -two important major targets for memory-support. In addition, PTI-00703 cat’s claw was the most effective cat’s claw (Uncaria tomentosa) ingredient for reducing /disaggregating and inhibiting Aβ 1–42 fibrils and tau protein paired helical/straight filaments in comparison to 17 other manufacturers of cat’s claw extracts tested.
... Gmel. 3 Popularly known as cat's claw, "unha-de-gato" (Brazil) or "uña de gato" (Spanish America), both of them have been indistinctly used for the same purposes in traditional medicine, such as to treat gastritis, gastric ulcers, cancer, arthritis, asthma and inflammatory conditions. [4][5][6] Previous chemical studies of U. guianensis revealed indole and oxindole alkaloids (low content), [7][8][9][10][11] proanthocyanidins, 12 flavonoids, and chlorogenic acid, 11,13 triterpenoid glycosides and sterols. [13][14][15] In vitro and clinical studies using a decoction of U. guianensis bark have corroborated its traditional use as an anti-inflammatory and antioxidant. ...
... [13][14][15] In vitro and clinical studies using a decoction of U. guianensis bark have corroborated its traditional use as an anti-inflammatory and antioxidant. 12,16 Bioassay-guided fractionation of the EtOH extract from the U. guianensis bark using a yeast-based assay for deoxyribonucleic acid (DNA)-damaging agents led to two weak but selectively active oxindole alkaloids. 17 Quinovic acid glycosides were also correlated with the observed anti-inflammatory activity of the species. ...
Article
Full-text available
The Amazonian Rubiaceae species Uncaria guianensis (UG) is locally used as antiinflammatory, antitumor, antidiabetic, anti-ulcers, and others. The phenolic content of its leaves is characterized by the great predominance of the flavonoid kaempferol-3,7-O-(α)-L-dirhamnoside (kaempferitrin). The present study quantitatively evaluates the kaempferitrin content in the leaves and branches of cultivated and wild UG specimens collected in different locations of the Brazilian Amazon rainforest by employing high-performance liquid chromatography coupled to a diode array detector (HPLC-DAD). Besides, the understanding of the polyphenol profile performed by electron spray ionization is deepened by tandem mass spectrometry analysis (ESI-MS/MS), using a previously approached leaf UG extract, and the flavonoid quercetin-3,7-O-(α)-L-dirhamnoside was first isolated from UG. All samples showed quite similar qualitative polyphenol profiles. Kaempferitrin in UG ranged from 1.1 to 1.9 mg 100 mg-1 for dry leaves of adult wild plants, 0.3 to 0.7 mg 100 mg-1 for dry leaves of cultivated young plants and 0.00 to 0.04 mg 100 mg-1 for dry branches of adult wild plants. Besides suggesting the distribution of kaempferitrin in the species, these results reinforce this flavonol as a suitable chemical marker for UG leaves and the products derived from them.
... Medicinal plants are sources of molecules recognized by medicinal chemists and pharmacologists. Research that considers the bioactive potential of compounds derived from medicinal plants shows the support for physicians and pharmacologists in the characterization and development of new drugs from natural sources [5,6]. ...
... The molecules (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were designed to calculate the physicochemical properties of the ionization constant (pKa), partition coefficients (logP), distribution (logD), and solubility (logS), as well as the extensive properties of molecular weight (MW), acceptors and H-bond donors (HBA and HBD), the number of rotatable bonds (Nrot) and topological polar surface area (TPSA) [22] in JS MarvinSketch version 21.3 software, ChemAxon (https://chemaxon.com/products/marvin) and then applied to the drug-likeness filters of the "rule of five" (RO5) of Lipinski (2004) [23] and to the rule of Veber et al., (2002) [24] and the oral bioavailability criteria by the method of Martin (2005) [25]. ...
Article
Bioprospecting has contributed to the work of pharmaceutical chemists in the development and commercial disposal of new drugs. Currently, the pharmaceutical industry has emphasized drugs produced from bioactive compounds extracted from natural sources, based on popular medicine discussed in the literature, such as secondary metabolites isolated from the stem bark and seeds of the Amburana cearensis, rich in coumarin derivatives, flavonoids, and phenolic acids and is popularly used in the treatment of respiratory diseases and with anti-inflammatory and antioxidant bioactivity. This review is a study of the structure/activity and structure/property (SAR/SPA) relationship with the physicochemical properties calculated by the algorithms of the MarvinSketch software for the secondary metabolites of A. cearensis, as well as their correlation with in silico test values the SwissADME and admetSAR 2.0 servers and in vitro and in vivo models of the dataset from the PreADMET, GUSAR Online and PASS Online servers. The results showed that substances derived from coumarin, flavonoids, and phenolic acids have attributes of good permeability and low efflux, which favor their oral bioavailability, since phenolic heterosides, amburoside analogs, and biflavonoids are effective in local action as subcutaneous application, constituting promising antimicrobial, anti-inflammatory and antioxidant therapeutic actions in their proper administration routes.
... The Uncaria tomentosa preparations are often used because of their anti-inflammatory activity, related to more than one secondary metabolite classes and can act synergistically [4] in possible pathways for anti-inflammatory actions to immunomodulation via suppression of TNF-α synthesis [9]. The prevention of the production of the transcription factor NF-kβ (nuclear factor kappa B) inhibiting the transcription of genes associated with the inflammatory process was also described [9][10][11]. The Uncaria tomentosa herbal medicine is considered a potent phytomedicine because it has immunomodulatory [12] and anti-amyloidosis activities against Alzheimer's disease and is a potent inhibitor and reducer of beta-amyloid fibrils and filaments (helical fibrils paired with tau proteins) [13]. ...
... The Uncaria tomentosa herbal medicine is considered a potent phytomedicine because it has immunomodulatory [12] and anti-amyloidosis activities against Alzheimer's disease and is a potent inhibitor and reducer of beta-amyloid fibrils and filaments (helical fibrils paired with tau proteins) [13]. The Uncaria tomentosa is a potent antioxidant [9,11,14] and also used in the treatment of gastritis and gastric ulcer; arthritis and rheumatism, skin diseases [5,10,15], antitumor actions against cancer [16]. Other potential pharmacological application of Uncaria tomentosa is on the asthma [5]. ...
Article
Full-text available
This work prepared and characterized microcapsule of Uncaria tomentosa (UT) in order to standardize a spray-dryer Uncaria tomentosa extract. The UT bark powder was subjected to extraction by maceration using hydro-ethanol solution. The Uncaria tomentosa extract was used to prepare the spray-dryer microcapsules UT-F1. The UT extract and microcapsules UT-F1 were submitted to chemical and physicochemical characterization tests. The phytochemical tests revealed the presence of alkaloids and phenolic compounds such as catechin. The UT extract and microcapsules UT-F1 showed high content of total phenols (28.48% ± 0.76 and 36.34% ± 0.22), high catechin content (47.95% ± 4.90 and 51.15% ± 4.20) and high antioxidant activity with IC50 values of 5.80 and 5.03 µg cm−3. The SEM, FTIR and TG analysis confirmed the morphology of spherical particles, the microencapsulation of the constituents of the UT extract, low moisture content, as well as stability of the microcapsules UT-F1. The DSC analysis and dissolution tests showed the technological influence of spray-dried starch combined UT extract considered water-poorly soluble resulting in vitro release (52.9%) of polyphenolic compounds from Uncaria tomentosa microcapsules. The combined use of disintegrants with a natural surfactant in the UT microcapsules has improved the release of polyphenols (catechin) from spray-dryer herbal composition reaching an equivalent release of 78.6% of catechin after 240 min. The in vitro release of microcapsules UT-F1 responds depending on the concentration of pharmaceutical excipients considered disintegrating and can easily achieve release greater than 80%. The microcapsules UT-F1 can be used as bulk material for herbal products in pharmaceutical industry.
... These plant components exist as complex mixtures of many medicinal metabolites, such as alkaloids, glycosides, terpenoids, phenols, flavonoids, and lignans [1]. Medicinal the identification and characterization of bioactive compounds from natural sources [2]. There have been growing interests in the toxicity of substances purified from plants basically to determine their safety [3 -5]. ...
Article
Full-text available
bwt) orally for a period of 9 days. The concentration of fasting blood glucose (FBG) was used as the therapeutic index. The results of the analysis revealed that total saponins isolated from the stem bark of D. guineense significantly reduced the Fasting Blood Glucose (FBG) levels of normal Wistar rats (p < 0.05). The graded and quantal dose-response curves showed that 150 mg/kg bwt was effective in reducing the blood glucose of rats (produced the best hypoglycemic effect). The study concluded that total saponins isolated from the stem bark of D. guineense possesses hypoglycemic effect at a relatively good dose.
... Such side effects motivate scientists to undertake studies to find a new source to treat inflammation which has minimal adverse effects. Nature provide such source in the form of herbal plants because isolated compounds from natural sources are bioactive (Sandoval et al., 2002) and thus possess many biological properties such as anti-inflammatory and anti-oxidant properties. ...
Article
Full-text available
Methanolic extracts of selected medicinal plants were tested to evaluate in vivo anti-inflammatory and in vitro antioxidant potential. For anti-inflammatory activity, carrageenan induced paw edema method was applied using albino rats. The observations were carried out at different doses including 250 ml/kg and 500 ml/kg. The potent anti-inflammatory activity was depicted by Viscum album and Withania coagulans at 500 mg/kg dose. Although the extracts showed significant effect at both doses, stronger anti-inflammatory effect was obtained at 500 mg/kg dose. The plant extracts had better anti-inflammatory activity as compared to Diclofenac (50 mg/kg). Using DPPH analysis, the plant extract of Sophora flavescens and Morus nigra showed potential antioxidant effect. Although a potent result was obtained from each methanolic extract but it was significantly different from Vitamin C. Thus, it can reasonably be concluded that these plants showed significant responses against inflammation and oxidation processes and can be further investigated for the isolation of biological constituents.
... The preclinical assessment revealed that the cat's claw defends toward various oxidative stresses, involving peroxynitrite that has been included in arthritis and other chronic inflammatory diseases along with inhibiting acute or chronic gastritis caused by high doses of nonsteroidal anti-inflammatory drugs (NSAIDs) [22,23]. U. tomentosa aqueous extract was found to protect against oxidative stress in human erythrocytes and relieve chronic intestinal inflammation in rats caused by indomethacin [24,25]. Another study documented that hydroxybenzoic acids, proanthocyanidins acids hydroxycinnamic were responsible for potent radical scavenging and anti-inflammatory activities of the cat's claw [26,27]. ...
... Cat , s claw ethyl acetate extracts , induction of apoptosis in HL-60 cells may make it excellent in the development of medicine that can trigger chemopreventive actions [81]. The presence of pentacyclic or oxindole alkaloids did not influence the antioxidant and anti-inflammatory properties of cats claw [82]. Natural compound Uncaria tomentosa acts as a safe antiresorptive candidate, and its anti-osteoclastogenic impact correlates with the reduction of chemical mediators of inflammation [83]. ...
Article
The world needs a paradigm change from the current views on many plants to secure both future food and nutrition. Many neglected and underutilized plants, specially medicinal and aromatic plants, are nutrient dense, appropriate in diversifying diets, provide enough vitamins and micronutrients for people, high resistant to diseases and pests, and can be adapted in many regions and of course with tremendous pharmaceutical benefits. Many of the medicinal plant species which were common in traditional medicine, are still neglected and underutilized, especially in developing and under-developing countries. Lack of attention to these plants means that their potential medicinal properties underexploited and underestimated. The searches focused on publications from 1980 to July 2021 using PubMed, Google Scholar, Science Direct, and Scopus databases. Review of the literature was carried out according to the keywords, "medicinal plants", "neglected plants", "underutilized plants", "aromatic plants", "traditional medicine science", and "South America". In this review article, the authors have focused on medicinal values of Schinusterebinthifolius, Uncaria tomentosa, Phyllanthusamarus, Astrocaryum aculeatum, Croton cajucara, Arrabidaea chica, Bauhinia forticata, Copaifera langsdorffii, Cordia verbenacea, Caesalpinia ferrea, Salix alba L., Casearia sylvestris, Carapa guianensis, Costus spicatus, and Eugenia uniflora L., in both modern and traditional science. Although many studies have evaluated the biological characteristics of these plants, little has been done to identify and characterize its chemical components, which is certainly a niche that requires to be further explored.
... The preclinical assessment revealed that the cat's claw defends toward various oxidative stresses, involving peroxynitrite that has been included in arthritis and other chronic inflammatory diseases along with inhibiting acute or chronic gastritis caused by high doses of nonsteroidal anti-inflammatory drugs (NSAIDs) [22,23]. U. tomentosa aqueous extract was found to protect against oxidative stress in human erythrocytes and relieve chronic intestinal inflammation in rats caused by indomethacin [24,25]. Another study documented that hydroxybenzoic acids, proanthocyanidins acids hydroxycinnamic were responsible for potent radical scavenging and anti-inflammatory activities of the cat's claw [26,27]. ...
Article
Full-text available
Uncaria tomentosa (Willd. ex Schult.) DC. (Family: Rubiaceae), commonly known as cat’s claw, is a tropical medicinal vine originating at the Amazon rainforest and other areas of South and Central America. It has been traditionally used to treat asthma, abscesses, fever, urinary tract infections, viral infections, and wounds and found to be effective as an immune system rejuvenator, antioxidant, antimicrobial, and anti-inflammatory agent. U. tomentosa is rich in many phytoconstituents such as oxindole and indole alkaloids, glycosides, organic acids, proanthocyanidins, sterols, and triterpenes. Biological activities of U. tomentosa have been examined against various microorganisms and parasites, including pathogenic bacteria, viruses, and Plasmodium, Babesia and Theileria parasites. Several formulations of cat’s claw (e.g., tinctures, decoctions, capsules, extracts, and teas) are recently available in the market. The current review covers the chemical constituents, biological activities, pharmacokinetics, and toxic properties of U. tomentosa extracts.
... The levels of NF-κβ, COX-1, PLA2, CCL2, and CCL5 mRNA were also reduced in RAW 264.7 (macrophage) cells when compared to cells stimulated with LPS. The results obtained suggest that the anti-inflammatory action of Miodesin™ is due, at least in part, to the action of the components of its formulation, either by the action of astaxanthin, reducing proinflammatory cytokine secretion, e.g., IL-1β, IL-6, and TNF-α, and reducing NF-κβ nuclear expression [49,50]; by the action of Uncaria tomentosa, promoting the inhibition of interleukins such as IL-1β, IL-17, and TNFα, in addition to the inhibition of NF-κβ [10,51,52]; or by the action of Endopleura uchi [27,53], inhibiting the action of cyclooxygenases (COX-1 and COX-2) and phos-pholipase A2 (PLA2), reducing the production of proinflammatory cytokines (IFN-γ and TNF-α). Our results, therefore, show the anti-inflammatory activity of Miode-sin™, by regulating the expression and/or secretion of several important inflammatory biomarkers. ...
Article
Full-text available
Purpose: To investigate the effects of a combined herbal medicine Miodesin™ on the inflammatory response of key cells involved in the acute and chronic inflammatory processes as well as the possible epigenetic involvement. Methods: After the establishment of the IC50 dose, the chondrocyte, keratinocyte, and macrophage cell lines were pretreated for 2 hours with Miodesin™ (200 μg/mL) and stimulated with LPS (1 μg/mL) for 24 hours. The supernatant was used to measure the levels of cytokines (IL-1β, IL-6, IL-8, and TNF-α) and chemokines (CCL2, CCL3, and CCL5), and the cells were used to extract the mRNA for the transcription factor (NF-κβ), inflammatory enzymes (COX-1, COX-2, PLA2, and iNOS), and chemokines (CCL2, CCL3, and CCL5). Results: Miodesin™ inhibited the release of LPS-induced cytokines (IL-1β, IL-6, IL-8, and TNF-α; p < 0.01) and chemokines (CCL2, CCL3, and CCL5; p < 0.01) and the expression of the transcription factor (NF-κβ; p < 0.01), inflammatory enzymes (COX-1, COX-2, PLA2, iNOS; p < 0.01), and chemokines (CCL2, CCL3, and CCL5; p < 0.01). In addition, the evaluation of epigenetic mechanism revealed that Miodesin™ did not induce changes in DNA methylation, assuring the genetic safeness of the compound in terms of the inflammatory response. Conclusions: Miodesin™ presents anti-inflammatory properties, inhibiting hyperactivation of chondrocytes, keratinocytes, and macrophages, involving epigenetics in such effects.
... Other clinical studies have found that the decoction of Tripterygium wilfordii Hook F developed adverse effects (Cai and Guo., 1974;Jian and Zhou, 1987). A study has shown that the herbal tea Guianensis inhibits the tumor necrosis factor (TNF) production involved in arthritis (Sandoval et al., 2002). Recent studies revealed that WS herbal tea effectively reduces arthritis syndrome without any toxic effect. ...
Article
Full-text available
Herbal teas or tisanes, like all foods of plant origin, start to take an important consideration in new product development in the recent years. This based on the increased awareness of their health benefits. It’s widely known that large number of medicinal plants of are exist world-wide, research in product development of herb teas is limited. However, herbal teas can exhibit also serious negative. Therefore, consumption must be set under some sort of medical control. Other issue is the quality control of herbal teas which govern the decision of the acceptance or rejection of the raw materials and finished products. Quality control methods of herbal teas is not limited to traditional macroscopic and microscopic analysis of the plant but should include new analytical methods such as high performance liquid chromatography, gas chromatography (HPLC), nuclear magnetic resonance (NMR) and many other new analytical tools for qualitative and quantitative analysis of the plant compounds. The latter facilitated the study of herbal teas as well as benefits and risks of on the consumer health. The present review aims at shedding light on the positive and negative effects of herbal teas with particular references to those in the Algerian market.
... Alternative medicine has been used in many countries to treat many illnesses and alleviate pain. This type of medicine depends mainly on the medicinal plants which are well known sources of bioactive compounds that have many pharmacological and medical benefits (Sandoval et al., 2002). ...
Article
Full-text available
An in-vitro evaluation of the antioxidant activities of wild Palestinian Pistacia palaestina extracts was done. In parallel, the total phenolic content (TPC) and the total flavonoids content (TFC) were measured. The antioxidant activities were determined spectrophotometrically by DPPH, FRAP, CUPRAC and the ABTS methods. The phenolic and flavonoid contents were separated and identified using LC-PDA-MS. The P. palaestina extract was found to contain many phenolic and flavonoids that enhance its reducing activity and free radical scavenging ability. Total phenolic content, and total flavonoids contents were found to be 66.5 ± 2.2 mg Gallic acid/g, and 20.3 ± 1.1 mg catechin/g, respectively. Antioxidant activity represented as FRAP, CUPRAC, DPPH and ABTS was found to be 23.5± 1.2 mmol Fe +2 /g, 4562 ± 63 µmol Trolox/g, 344 ± 11 µmol/g, 53.1 ± 6.6 µmol/g, respectively. The aim of the study is therefore to employ different antioxidant tests to evaluate the antioxidant activities of crude ethanol leaf extracts of P. palaestina, and to determine its phenolic and flavonoids content.
... It usually used as one of the traditional medicinal plants and now already commercialized (Valerio and Gonzales, 2005). Commonly, people take the benefit of the cat's claw by the bark and root; also, some utilize the leaves for therapeutic natural materials (Sandoval et al., 2002). People used this liana for treating some diseases associated with inflammation, such as abscesses, infection, fever, wounds (Batiha et al., 2020;Deharo et al., 2004). ...
Article
Full-text available
Uncaria tomentosa is one natural medicinal plant. The plant parts commonly harvested and utilized are the leaves and twigs. This study aimed to find out the benefit of the hook of U. tomentosa regarding the antibacterial and anti-inflammatory produces by phytochemical content. It was a Laboratory-based study. The primary material was the hooks of U. tomentosa (Wild. Ex Schult) DC collected from Kapuas Hulu, West Kalimantan, Indonesia, and extracted by Ethanol and Methanol maceration. The antibacterial was determined against Staphylococcus aureus and Salmonella Thypi; measured the transparent zone after 24 H incubation at 37 ºC. The anti-inflammatory activity was identified on the stability of red blood cells (RBCs) membrane by determining the percentage of hemolysis inhibition. The observation showed that ethanol extract had better phytochemical substances compared to methanol extract, and became a selected sample intended for antibacterial and anti-inflammatory identification. The higher concentration of ethanol extract led to an increased in bacterial growth inhibition. The ethanol extract showed a better impact against RBCs stability at level ≥ 50 ppm compared to 100 ppm aspirin with the EC50 was 5.21 ppm. The result indicates that ethanol extract derived from the hooks of Uncaria tomentosa (Wild. Ex Schult) DC origin Kalimantan, Indonesia provides the antibacterial and anti-inflammatory at once.
... Investigation of novel different medicinal plants from different regions of the world and their botanical utilization has increased all over the world including western world. We have a mechanistic information deficiency and a lack of possible differences amongst species from the same genus of a plant [4]. ...
Article
Full-text available
Background: This experiment is conducted to evaluate the anti-inflammatory effect of Piper chaba roots. Methods: The in-vitro anti-inflammatory activity of Piper chaba was carried out by human red blood cell (HRBC) membrane stabilization method which includes heat-induced hemolysis and hypotonicity- induced hemolysis and also by another method of egg albumin denaturation assay. Results: Anti-inflammatory activity study of crude ethanolic extract was performed using heat induced membrane stabilization method, hypo-tonicity induced HRBC membrane stabilization method and egg albumin denaturation method. Crude ethanolic extracts of P. chaba showed promising in vitro anti-inflammatory activity in a concentration dependent manner. Using acetyl salicylic acid (ASA) as standard drug and was compared with ethanolic extract to determine anti-inflammatory activity. Heat induced anti-inflammatory test revealed that crude ethanolic extract of P. chaba (500 μg/ml) and positive control ASA(500 μg/ml) have 52.667% and 78% respectively, hypo tonicity induced anti- inflammatory test showed 35.67% and 59% inhibition of red blood cell (RBC) hemolysis. Egg albumin denaturation method also evaluated that crude ethanolic extract (1000 μg/ml) and ASA (1000 μg/ml) showed 60% and 97.12% inhibition of egg albumin denaturation. Conclusion: The plant of P. chaba of the genus Piper possesses promising anti-inflammatory activities.
... In many countries, such as Germany and Austria, standardised extracts from the root of U. tomentosa, in powder form, are used 2-3 times a day at doses from 20 to 60 mg/day (Falkiewicz and Lukasiak, 2001). U. tomentosa has become highly popular in many other countries due to its proven immunostimulatory and anti-inflammatory activities (Allen-Hall et al., 2010;Della Valle et al., 2017;Azevedo et al., 2018;Elgawish et al., 2019;Sandoval et al., 2000Sandoval et al., , 2002Sheng et al., 2000) as well as due to its antioxidative (Bors et al., 2011;Bukowska et al., 2012;Kośmider et al., 2017;Azevedo et al., 2019;Navarro et. 2019), antimutagenic (Almeida et al., 2017), antigenotoxic (Santo et al., 2018;Navarro-Hoyos et al., 2017) and anticarcinogenic properties (Pilarski et al., 2010;Almeida et al., 2017;Ciani et al., 2018). ...
Article
Ethnopharmacological relevance A wide range of traditional medicine applications of Uncaria tomentosa (Willd. ex Schult.) DC., commonly known as ‘vilcacora’ or ‘cat's claw’, includes blood purification, its anticoagulant properties and its use in haemorrhage therapy. Aim of the study Our work is devoted to the effects of ethanol and aqueous extracts (1–50 μg/ml) from U. tomentosa leaves and bark on the haemostatic system. The study is based on two main questions: Can these extracts influence the coagulation cascade of blood plasma or the activation of blood platelets? Do they feature any anticoagulant properties? Materials and methods Blood platelet aggregation was measured in human platelet-rich plasma; the anticoagulant tests were based on the thrombin, prothrombin and the activated partial thromboplastin time. For the thrombin (TH)-inhibitory activity evaluation, the chromogenic substrate S-2238 and fibrinogen, i.e. physiological substrate for this enzyme, were used. In silico studies included the interactions of TH and the main components of the extracts. Results The examined extracts demonstrated slight antiplatelet activity. The thrombin time was slightly prolonged. The most efficient TH inhibitor was the ethanolic fraction from leaves (IC50 = 5.86 and 12.48 μg/ml, for the amidolytic and proteolytic assay, respectively). The plant ingredients interacted with TH within and outside the active site, dependently on the compound. The higher binding affinity was found for procyanidins B2 and C1. Conclusions The examined extracts demonstrated slight antiplatelet effects; however, they may be promising candidates for the natural inhibitors of TH, which is critical for the formation of fibrin clot.
... The group has previously reported a similar chemical profile while analyzing extracts of barks and leaves from U. tomentosa, especially mitraphylline (de Azevedo et al., 2018). Although the anti-inflammatory effect of Uncaria species can be mostly attributed to its mitraphylline content, other alkaloids are present and may contribute to the effect, such as rhynchophylline, isorhynchophylline, speciophylline and uncarine E (Sandoval et al., 2002). Additionally, a significant amount of quinic acid, which is a compound responsible for the anti-inflammatory activity in commercial extracts of U. tomentosa was detected (Åkesson et al., 2005). ...
Article
Full-text available
Uncaria guianensis (Aubl.) J. F. Gmel. (“cat’s claw”, Rubiaceae) is a plant with potential to treat asthma because of its anti-inflammatory and antioxidant activities. The aim of this study was to evaluate the effects of two extracts of U. guianensis in an animal model of allergic asthma. Balb/c mice were sensitized twice with ovalbumin intraperitoneally one week apart, then challenged with intranasal ovalbumin for three days. Animals were treated with aqueous or hydroethanolic extracts (100 mg/kg) for three days, simultaneously with ovalbumin challenges. Control mice received saline solution on the same days. In vivo bronchial hyper responsiveness, airway and lung inflammation, IgE levels, and total antioxidant capacity were measured. Treatment with the hydroethanolic extract significantly reduced total cell and eosinophil counts in bronchoalveolar lavage, and in vivo bronchial hyper responsiveness. Moreover, U. guianensis hydroethanolic extract significantly reduced interleukin 13 levels in lung homogenate. Total antioxidant capacity and IgE serum levels were not affected with the extract administration. Of note, treatment with the aqueous extract did not elicit significant effects on asthma-like characteristics. Only the hydroethanolic extract of U. guianensis reduced lung inflammation and bronchial hyper responsiveness in asthmatic mice
... 14 Chemical composition of U. tomentosa U. tomentosa is used in Perù and Europe and since 1994 the WHO recognized this plant as an adjunctive treatment for cancer and other diseases. 15 The edible part of U. tomentosa is the bark that in the pharmaceutical industry is processed into capsules, tablets, ointments, and even tea. ...
Chapter
Uncaria tomentosa, called “uña de gato,” belonging to the Rubiaceae family, is a thorny liana that grows wild in the upper Amazon region of Peru and neighboring countries. The indigenous people of Amazonian rain forest have used its root/bark over the centuries for the treatment of several diseases, and this plant is believed to have antioxidant, anti-inflammatory, and antitumoral properties. Many active compounds have been isolated from U. tomentosa, including antioxidants such as tannin, catechins, procyanidins, sterols, triterpenes, flavonoids, carboxyl alkyl esters, and indole and oxindole alkaloids. In particular, alkaloids, the major active components of Uncaria species, have been extensively studied for their potential use as anticancer agents. In this chapter, some aspects of the actions of U. tomentosa on oxidative stress and cancer have been discussed, after having characterized the plant and mentioned the biochemistry of oxidative stress.
... Thus, we hypothesized that plant extracts with known anti-inflammatory effects, may contain active compounds with senolytic and/or senomorphic properties. To this end, we screened extracts from four plants with well-established anti-inflammatory properties [17,18], including extracts from Harpagophytum procumbens (Devil's Claw), Uncaria tomentosa (Cat's Claw) [19], Zingiber officinale Rosc. (ginger) [20] and Solidago canadensis (Canadian Goldenrod). ...
Article
Full-text available
Senescent cells accumulate with aging and have been shown to contribute to age-associated diseases and organ dysfunction. Eliminating senescent cells with senolytic drugs has been shown to improve age phenotypes in mouse models and there is some initial evidence that it may improve the health of persons with chronic diseases. In this study, we employed WI-38 human fibroblasts rendered senescent by exposure to ionizing radiation (IR) to screen several plant extracts for their potential senolytic and/or senomorphic activity. Of these, ginger extract ( Zingiber officinale Rosc .) selectively caused the death of senescent cells without affecting proliferating cells. Among the major individual components of ginger extract, gingerenone A and 6-shogaol showed promising senolytic properties, with gingerenone A selectively eliminating senescent cells. Similar to the senolytic cocktail dasatinib and quercetin (D+Q), gingerenone A and 6-shogaol elicited an apoptotic program. Additionally, both D+Q and gingerenone A had a pronounced effect on suppressing the senescence-associated secretory phenotype (SASP). Gingerenone A selectively promotes the death of senescent cells with no effect on non-senescent cells and these characteristics strongly support the idea that this natural compound may have therapeutic benefit in diseases characterized by senescent cell accumulation.
... The results of several studies suggested that supplementation with polyphenols and botanical extracts (e.g., Boswellia serrata extract, PFP, ParActin, ART and cat's claw extract) decrease the serum levels of TNF-α and MMP-3 in synovial fluid in patients with knee OA compared with the control groups 53,70,71 . Cellular and animal models have suggested also the benefits of such compounds and food ingredients (e.g., probiotics) in inhibiting inflammatory paths and reducing the production of iNOS, COX-2 and MMP enzymes to decrease the catabolic destruction of the cartilage 16,[72][73][74][75][76] . ...
Article
Full-text available
This study designed to evaluate the effect of nutraceutical supplementation on pain intensity and physical function in patients with knee/hip OA. The MEDLINE, Web of Science, Cochrane Library, Scopus, EMBASE, Google Scholar, Science direct, and ProQuest in addition to SID, Magiran, and Iranmedex were searched up to March 2020. Records (n = 465) were screened via the PICOS criteria: participants were patients with hip or knee OA; intervention was different nutritional supplements; comparator was any comparator; the outcome was pain intensity (Visual analogue scale [VAS]) and physical function (Western Ontario and McMaster Universities Arthritis [WOMAC] index); study type was randomized controlled trials. The random effects model was used to pool the calculated effect sizes. The standardized mean difference (SMD) of the outcome changes was considered as the effect size. The random effects model was used to combine the effect sizes. Heterogeneity between studies was assessed by Cochran's (Q) and I2 statistics. A total of 42 RCTs were involved in the meta-analysis. Nutritional supplementation were found to improve total WOMAC index (SMD = − 0.23, 95% CI − 0.37 to − 0.08), WOMAC pain (SMD = − 0.36, 95% CI − 0.62 to − 0.10) and WOMAC stiffness (SMD = − 0.47, 95% CI − 0.71 to − 0.23) subscales and VAS (SMD = − 0.79, 95% CI − 1.05 to − 0.05). Results of subgroup analysis according to the supplementation duration showed that the pooled effect size in studies with < 10 months, 10–20 months and > 20 months supplementation duration were 0.05, 0.27, and 0.36, respectively for WOMAC total score, 0.14, 0.55 and 0.05, respectively for WOAMC pain subscale, 0.59, 0.47 and 0.41, respectively for WOMAC stiffness subscale, 0.05, 0.57 and 0.53, respectively for WOMAC physical function subscale and 0.65, 0.99 and 0.12, respectively for VAS pain. The result suggested that nutraceutical supplementation of patients with knee/hip OA may lead to an improvement in pain intensity and physical function.
... It has been proven that polyphenols isolated from U. tomentosa exhibit very strong antioxidative properties. Several reports have shown that aqueous and methanolic extracts obtained from different parts of U. tomentosa protected cells from free radicals production and lipid peroxidation in vitro, as well as inhibited free radical-induced DNA damage and cell death [2,3,31]. In our previous study we also showed that U. tomentosa extracts under physiological conditions protected erythrocytes against ROS formation and hemolysis. ...
Article
Full-text available
Uncaria tomentosa (Willd.) DC is a woody climber species originating from South and Central America that has been used in the therapy of asthma, rheumatism, hypertension, and blood purification. Our previous study showed that U. tomentosa extracts altered human erythrocyte shape, which could be due to incorporation of the compounds contained in extracts into the erythrocyte membrane. The aim of the present study was to determine how the compounds contained in U. tomentosa extracts incorporate into the human erythrocyte membrane. The study has assessed the effect of aqueous and ethanolic extracts from leaves and bark of U. tomentosa on the osmotic resistance of the human erythrocyte, the viscosity of erythrocyte interior, and the fluidity of erythrocyte plasma membrane. Human erythrocytes were incubated with the studied extracts in the concentrations of 100, 250, and 500 µg/mL for 2, 5, and 24 h. All extracts tested caused a decrease in erythrocyte membrane fluidity and increased erythrocyte osmotic sensitivity. The ethanolic extracts from the bark and leaves increased viscosity of the erythrocytes. The largest changes in the studied parameters were observed in the cells incubated with bark ethanolic extract. We consider that the compounds from U. tomentosa extracts mainly build into the outer, hydrophilic monolayer of the erythrocyte membrane, thus protecting the erythrocytes against the adverse effects of oxidative stress.
... Study Type Function/Outcome Measure Reference Ashwagandha (Withania somnifera) in vitro, in vivo, clinical studies antioxidant, anti-inflammatory, blocks Aβ production, inhibits neural cell death, dendrite extension, neurite outgrowth and restores synaptic function, neural regeneration, reverses mitochondrial dysfunction, improves auditory-verbal working memory, executive function, processing speed, and social cognition in patients [20,[23][24][25][26][27][28][29] Brahmi (Bacopa monnieri) in vitro, in vivo, clinical studies antioxidant, anti-inflammatory, improves memory, attention, executive function, blocks Aβ production, inhibits neural cell death, delays brain aging, improves cardiac function [30][31][32][33][34][35][36][37] Cat's claw (Uncaria tomentosa) in vitro, in vivo, pre-clinical studies anti-inflammatory, antioxidant, inhibits plaques and tangles, reduces gliosis, improves memory [38][39][40][41][42][43][44][45] Ginkgo biloba in vitro, pre-clinical, clinical studies antioxidant, improves mitochondrial function, stimulates cerebral blood flow, blocks neural cell death, stimulates neurogenesis [46][47][48][49][50] Gotu kola (Centella asiatica) in vitro, in vivo, clinical studies neuroceutical, cogniceutical, reduces oxidative stress, Aβ levels, and apoptosis, promotes dendritic growth and mitochondrial health, improves mood and memory [51][52][53][54][55][56][57][58] Lion's mane (Hericium erinaceus) in vitro, in vivo, pre-clinical and clinical studies neuroprotective, improves cognition, anti-inflammatory, blocks Aβ production, stimulates neurotransmission and neurite outgrowth [59][60][61][62][63] It is hoped that the historical knowledge base of traditional systems of medicine, coupled with combinatorial sciences and high-throughput screening techniques, will improve the ease with which herbal products and formulations can be used in the drug development process to provide new functional leads for AD. ...
Article
Full-text available
Background—Alzheimer’s disease (AD) is a multifactorial, progressive, neurodegenerative disease that is characterized by memory loss, personality changes, and a decline in cognitive function. While the exact cause of AD is still unclear, recent studies point to lifestyle, diet, environmental, and genetic factors as contributors to disease progression. The pharmaceutical approaches developed to date do not alter disease progression. More than two hundred promising drug candidates have failed clinical trials in the past decade, suggesting that the disease and its causes may be highly complex. Medicinal plants and herbal remedies are now gaining more interest as complementary and alternative interventions and are a valuable source for developing drug candidates for AD. Indeed, several scientific studies have described the use of various medicinal plants and their principal phytochemicals for the treatment of AD. This article reviews a subset of herbs for their anti-inflammatory, antioxidant, and cognitive-enhancing effects. Methods—This article systematically reviews recent studies that have investigated the role of neuroprotective herbs and their bioactive compounds for dementia associated with Alzheimer’s disease and pre-Alzheimer’s disease. PubMed Central, Scopus, and Google Scholar databases of articles were collected, and abstracts were reviewed for relevance to the subject matter. Conclusions—Medicinal plants have great potential as part of an overall program in the prevention and treatment of cognitive decline associated with AD. It is hoped that these medicinal plants can be used in drug discovery programs for identifying safe and efficacious small molecules for AD.
... Previous studies have stated differences between antioxidant profiles of leaves, barks, and roots (Bors et al., 2011). However, according to Sandoval et al. (2002), the EUt have a high capacity to inhibit DPPH radicals, regardless of which part of the plant is used. ...
Article
Full-text available
Uncaria tomentosa, a climbing vine notable for containing high concentrations of oxindole alkaloids and phenolic compounds, is commonly used in traditional medicine as an anti-inflammatory and antioxidant agent. Also, the citric acid is a food additive widely used for conservation, due to its low cost. In this way, this study aims to evaluate the content of phenolic compounds from Uncaria tomentosa and investigate its antioxidant activity when citric acid, at different concentrations, is added to the extract. For this purpose, a gradient of citric acid concentrations was established, and the antioxidant profile from a aqueous extracts of the plant leaves and bark was analyzed by Folin-Ciocalteu essay; inhibition of the free radical of 2,2-diphenyl-1-picrylhydrazyl (DPPH); ferric reducing antioxidant power (FRAP), and scavenging capacity of cationic free radicals of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS). The results showed a synergistic effect between citric acid and antioxidant compounds from Uncaria tomentosa, presenting highly statistical significance, the synergistic effect was more efficient in the bark than in the leaves.
... The determination of the active compounds of U. tomentosa, T. parthenium and B. serrata was performed by the supplier (A.C.E.F. Fiorenzuola d'Arda, Italy) using high-performance liquid chromatography (HPLC) [12][13][14][15][16][17][18][19][20][21][22][23][24]. ...
Article
Full-text available
Reducing the use of antibiotics in livestock in order to contain antibiotic resistance and studying natural substance additives are key to sustainability. Among the various biological activities of plant extracts, antioxidant activity plays an important role. The present study assesses the total antioxidant activity and antioxidant reserves using the Kit Radicaux Libres test (KRL™ Kirial International, Couternon, France). One hundred and sixty piglets (Topics × Tempo) weaned at 28 days of age were divided into four dietary treatment groups that were fed a commercial diet (the control group, C); 500 mg/kg Boswellia extract (BOS); 200 and 50 mg/kg Uncaria and Tanacetum extracts (UT) respectively; and 225 mg/kg of an antioxidant plant extract mixture (AOX). The blood antioxidant activity of the piglets was measured using the KRL test and the reserves were analyzed on whole blood samples after hydrolysis with glucosidase, sulfatase and glucuronidase. No significant differences were observed in growth performance. The delta KRL values of the whole blood showed a significantly higher total antioxidant status of the piglets from the BOS and AOX groups than the UT and C groups (+30.7 BOS; +27.7 AOX vs. +17.81 UT +13.30 C; p = 0.002) between 18 and 28 days post-weaning. The delta KRL values of red blood cells (RBCs) showed a significantly higher total antioxidant status of the piglets from the AOX groups than the UT and BOS groups (+22.2 AOX; vs. +9.90 UT +9.4 BOS; p = 0.016) between the two sampling times. Reserves of UT and AOX were higher than C and BOS for all enzymes, glucosides, sulphates, and glucuronides. The biological KRL test proved to be an extremely sensitive tool to evaluate the piglets’ antioxidant status. Determining the antioxidant reserve also provides a better understanding of the real antioxidant status of pigs.
... Inhibition of pro-inflammatory cytokines --Smilax galbra [48] Allium sativum [49] Harpagophytum procumbens [50] Pinus maritima [51] Astragalus membranaceus [52] Coptis spp. [53] Rosa davurica [54] Uncaria tomentosa [55] Coriolus versicolor [56] Curcuma longa [57] Modulation of pro-inflammatory gene expression ...
Article
Full-text available
One of the principal causes of different disorders is uncontrolled inflammatory response. Alkaloid, flavonoids, polyphenolic, proanthocyanidin, terpenoid and steroid compounds are the main reasons of anti-inflammatory activities of medicinal herbs and plants. The current manuscript introduces a series of potential anti-inflammatory plants, particularly those which are routines in Iranian and Chinese traditional herbal medicine, and simplify the function and mechanisms of natural constituents for prevention and treatment of inflammatory disorders. PubMed, Science Direct, Google Scholar, Wiley Online Library, Springer, Taylor and Francis, etc have been used to search for collecting of scientific publications for a full evaluation of current documentations I the literatures showing the importance of medicinal plants with anti-inflammatory characteristics and natural medicines. The most notable medicinal plants with anti-inflammatory activities are Baccharis dracunculifolia, Aconitum bulleyanum, Crateya adansonii, Alliums spp., Centella asiatica, Flos lonicerae, Corydalis dubia, Syringae folium, Coptis chinensis, Casearia decandra, Nigella sativa, Cannabis sativa, Tamarindus indica L., Glycyrrhiza glabra, Panax ginseng, Panax notoginseng, Pistacia vera, Smilax china, Scutellaria baicalensis, Rosemarinus officinalis, Moringa olifera, Pulsatilla radix, Pistacia atlantica, Rullia tuberose, Canarium album, Dodonaea polyandra, Forsythia suspense, Polygala tenuifolia, Radiz Isatidis, Hypericum sampsonii, Geranium koreanum, Typha capensis, Isatidis folium, Ginkgo biloba, Houttuynia cordata, snow lotus, and etc. Herbal medicine mainly uses numerous parts of plants or combinations of them to prevent and remedy diseases and promote health. More investigations and clinical experiments are needed to provide more information on the importance of medicinal plants as well as their roles for treatment and prevention of inflammatory diseases.
... Uncaria tomentosa derived from herbs having small claw-like thorns, is a medicinal plant from the family Rubiaceae [82] containing polyphenols, alkaloids, and sterols as the active components [68]. It possesses the ability to target epidermal growth factor receptors along with the downstream signaling pathways. ...
Article
Background The cyclooxygenase (COX) and lipoxygenase (LOX) enzymes catalyze the production of pain mediators like prostaglandins (PGs) and leukotrienes (LTs) respectively from arachidonic acid. Introduction The COX and LOX enzyme modulators are responsible for the major PGs and LTs mediated complications like asthma, osteoarthritis, rheumatoid arthritis, cancer, Alzheimer’s disease, neuropathy and cardiovascular syndromes (CVS). Many synthetic nonsteroidal anti-inflammatory drugs (NSAIDs) used in the treatment have serious side effects like nausea, vomiting, hyperacidity, gastrointestinal ulcers, CVS, etc. Methods The natural inhibitors of pain mediators have great acceptance worldwide due to fewer side effects on long-term uses. The present review is an extensive study of the advantages of plant-based vs synthetic inhibitors. Results These natural COX and LOX inhibitors control inflammatory response without causing side-effect-related complicacy. Conclusion Therefore, the natural COX and LOX inhibitors may be used as alternative medicines for the management of pain and inflammation due to their less toxicity and resistivity.
... (16) Os alcaloides oxindólicos contidos na uncaria tomentosa estão em maior concentração, quando comparada com Uncaria guianensis. (17) Estudos corroboram os benefícios da unha-de-gato. A atividade anti-inflamatória da Mitrafilina isolada da planta foi testada In-vivo e como resultado observou-se que, o principal alcaloide oxindólico, inibiu a produção do TNFα (Fator de necroses tumoral) em 50 % em ratos injetados com solução salina de endotoxinas de baterias gramnegativas (intraperitoneal). ...
Article
Full-text available
Introdução: A Uncaria tomentosa conhecida popularmente como unha-de-gato, é uma planta amazônica com propriedades benéficas e terapêuticas em humanos e animais. é utilizada em tratamentos de abcessos, artrites, asma, câncer, inflamação do trato urinário e prevenção de outras doenças. Objetivo: Avaliar o efeito da alimentação com Uncaria tomentosa (unha de gato) em Pterophyllum scalare (acará-bandeira) submetidos a estresse. Métodos: Foram utilizados 400 peixes com peso médio inicial de 0,48 ± 0,01g e comprimento padrão de 1,9 ± 0,13 cm, alimentados por 150 dias com cinco níveis de inclusão da planta na dieta 0; 75; 150; 300 e 450 mg de farinha de folhas de Uncaria tomentosa / kg de ração com quatro repetições em delineamento inteiramente casualizado. Foram realizadas biometrias dos peixes a cada 30 dias. Ao final do experimento os peixes foram submetidos a simulação de transporte por 24 horas. Finalmente, foram avaliados a glicemia, mortalidade e parâmetros físico-químicos da água. Resultados: Não houve diferença na glicemia nem nos parâmetros da qualidade da água entre os tratamentos após a uma simulação de transporte por 24 horas.
Article
Introduction Rapidly emerging diseases, such as viral infections, cancer, and autoimmune disorders are becoming an increasing global health concern. Natural products, including plant extracts and compounds, possess an enormous spectrum of pharmacological activities, including antiviral, anticancer, immunomodulatory, anti-asthma, anti-diabetic, anti-hypertension, and anti-rheumatism activities. Among them, the genus Uncaria (Rubiaceae family), rich in alkaloids and triterpenes, is believed to have vast therapeutic potential. This genus is mostly found in tropical regions, such as Africa, Southeast Asia, and Southeast America. In this review, we aim to summarize the studies on plant substances of genus Uncaria showing promising antimicrobial, anticancer, and immunomodulatory activities. Methodology A total of 814 studies were identified through database searches, of which 681 studies were excluded due to duplication and irrelevance to antimicrobial, immunomodulatory, and pharmacology activity. 133 studies were included, out of which 16 studies were related to antimicrobial and 117 studies related to the pharmacology of Uncaria. Conclusion According to the collected data Uncaria species proved to have a broad range of pharmacological activities, which makes it more interesting for further studies, to explore more about its antimicrobial, immunomodulatory, and other potential pharmacological properties.
Article
Phytotherapeutic preparations from Uncaria guianensis (Aubl.) J.F. Gmel. (Rubiaceae) are marketed worldwide and are mainly used for their anti-inflammatory activity. The species has not yet been domesticated and is threatened by deforestation and overexploitation. It is, therefore, important to preserve and manage this genetic resource in germplasm banks, so that the extractive provision of plant material can be replaced by cultivated production. The aim of this study was to evaluate the genetic diversity among 20 genotypes maintained under in vitro conditions using 9 primers start codon targeted (SCoT) polymorphism, and to determine the concentrations of the pentacyclic oxindole alkaloids (POAs); mitraphylline and isomitraphylline in methanolic extracts by high-performance liquid chromatography (HPLC). Plantlets were cultivated on woody plant medium supplemented with 20 g.L-1 sucrose and 4.4 μM benzylaminopurine and incubated under a 16 h photoperiod for 45 days. SCoT analysis separated the genotypes into four divergent clusters and confirmed significant genetic diversity with up to 70% dissimilarity. Moreover, HPLC revealed considerable chemical variability and allowed the separation of the tested genotypes into high, medium and low producers of mitraphylline/isomitraphylline. Genotypes with the highest concentrations of POAs originated from the state of Acre and Amapá, while those with the lowest levels were from the state of Pará. The results demonstrate that the genetic diversity within the in vitro germplasm bank is sufficient to support breeding studies, selection of elite genotypes and the large-scale multiplication of plants that could serve as feedstock for the industrial-scale production of phytomedicines. Supplementary information: The online version contains supplementary material available at 10.1007/s13205-021-03016-y.
Article
With growing popularity of complementary and alternative medicine (CAM) among the individuals with chronic pain and muscular problems, a number of patients with rheumatoid arthritis (RA) show their interest in CAM interventions for disease improvement. Various reports published on CAM are based on animal model of RA however there is often lack of high quality clinical investigations for explaining the success stories of CAM therapies in patients with RA. CAMs having potential to be used for therapy in patients with RA have been identified, however lack of awareness and scepticism of their efficacy has made the patients reluctant to choose these drug less therapies. In this review, we have summarized the existing evidences which suggest promising efficacy of different alternative therapies in managing RA and providing both physical and mental well being to RA patients.
Article
Fipronil (FIP) insecticide is extensively used in agriculture, public health and veterinary medicine. Although it is considered as a neurotoxin to insects (target organisms) and exhibits neurological signs upon vertebrates (non-target organisms) exposure, slight is known about its potential neurotoxic effects and its molecular mechanisms on vertebrates. The current study is designed to assess oxidative stress as a molecular mechanism of FIP neurotoxicity subordinated with apoptosis and neural tissue reactivity. Ten adult male albino rats received 10 mg/kg body weight fipronil technical grade by oral gavage daily for 45 days (subacute exposure). Brain neural tissue regions (hippocampus, cerebellum and caudate putamen) were processed to examine oxidative stress induced cellular macromolecular alterations as MDA, PCC and DNA fragmentation. Besides, TNF-α and Bcl-2 gene expression and immunoreactivity for caspase-3 (active form), iNOS and GFAP were evaluated. Also, histopathological assessment was conducted. We found that FIP significantly raised MDA, PCC and DNA fragmentation (p ≤ 0.05). Also, it significantly upregulated TNF-α and non-significantly down-regulated Bcl-2 gene expression (p ≤ 0.05). Further, significant increased immunoreactivity to GFAP, iNOS and caspase-3 (active form) in these brain neural tissue regions in FIP treated group was noticed (p ≤ 0.05). Histopathological findings, including alterations in the histological architecture and neuronal degeneration, were also observed in these brain regions of FIP treated group. In conclusion, we suggest the ability of FIP to induce oxidative stress mediated macromolecular alterations, leading to apoptosis and tissue reaction in these brain regions which showed variable susceptibility to FIP toxic effects.
Article
Full-text available
Background: Uncaria tomentosa (Will.) DC. It is known as "cat's claw", in traditional medicine it has anti-inflammatory, antiviral, immunostimulating and anti-tumor properties. They have bioactive pentacyclic and tetracyclic oxindole alkaloid type, as well as terpenes, flavonoids responsible for the therapeutic activity. The objective of this work reviews the botany, phytochemistry, obtaining, isolation and identification of bioactives, pharmacological activity and toxicity, medicinal properties and traditional uses regarding this species. Methods: Scientific database articles (Scopus, Scielo, academic Google) were compiled using keywords and connectors Uncaria tomentosa, ethnobotany, phytochemical, pharmacological activity, toxicity, medicinal properties, traditional use. Results: The search resulted in (457 in Scopus, 39 in Scielo and 8020 in academic google) between articles and related theses on the Uncaria tomentosa species, among them, 77 articles and theses of relevance for writing this review. Conclusions: Uncaria tomentosa shows its traditional use due to its important anti-inflammatory activity, this due to the oxindole pentacyclic alkaloid compounds that were described and supported by the scientific literature. This knowledge also fills a gap in the literature for the recognition of adulteration and, for the quality control of plant products and medicines from Uncaria tomentosa. Keywords: Native plant, Uncaria tomentosa, ethnobotany
Article
Osteoporosis is a chronic, progressive bone condition which is mostly prevalent in post-menopausal women and the elderly population. An imbalance in the natural bone remodeling process which is involved in the formation of bone and resorption is responsible for osteoporosis leading to bone fragility. It shows no clinical manifestation until a fracture takes place. Osteoporosis is a global epidemic which reduces quality of life, increases the chances of disabilities and adds on a huge financial load. Early diagnosis and treatment can help in preventing the disease. Several drug regimens are used in treating the condition however the drugs are accompanied by several adverse effects. Nutraceuticals like herbs, minerals, vitamins, dairy products and minerals support skeletal strength and integrity. Therefore, use of different types of nutraceuticals can improve overall bone strength and provide improved treatment of osteoporosis. The review paper focusses on providing in depth knowledge about the various nutraceuticals that are used in the management of osteoporosis along with the novel nanotechnology based delivery approaches for enhanced delivery of nutraceuticals as the advent of nanotechnology in pharmaceuticals have opened new avenues in the challenging arena of nutraceuticals for providing benefits like stability, higher efficiency, solubility, enhanced bioavailability, permeability and production without additives.
Book
Full-text available
Este volume da obra “Ciências Biológicas: Campo promissor em Pesquisa 4” vem trazer ao leitor, em seus capítulos, informações diversas imbuídas em diferentes campos do conhecimento de Ciências da Vida, como o próprio título do e-book sugere: uma área extremamente promissora, dinâmica e passível de aquisição de novas informações a todo momento, vindo, de forma comprometida e e caz, a atualizar o leitor interessado nesta grande área do conhecimento. Pesquisadores de diferentes gerações, e diferentes regiões do país, motivados por uma força motriz que impulsiona a busca de respostas às suas perguntas, trazem dados resultantes da dedicação à Ciência, ansiando responder suas inquietações e compartilhar com o leitor, de forma cristalina e didática, seus alcances técnico-cientí cos, satisfazendo a função precípua da ciência que é a de melhorar a qualidade de vida do homem, enquanto executante do seu papel cidadão e ser social. Somente por uma questão de ordenação, os 28 capítulos deste volume foram sequenciados levando-se em consideração, primeiramente, estudos, em diferentes vertentes, com organismos vivos, animais e plantas, seguidos por pesquisas oriundas de aspectos didático-pedagógicos, aquelas relacionadas aos progressos de situações-problemas em vegetais, animais e humanos e, por m, interações entre diferentes organismos no espaço ambiental com um todo. Em todas estas áreas, as pesquisas conduzem o leitor a acompanhar descobertas/ avanços que proporcionam, indubitavelmente, um quadro mais robusto, e que acresce ao que até então se tem conhecimento naquele campo de estudo, das diferentes subáreas das Ciências Biológicas, com viés também para a saúde e bem estar humanos. Neste sentido, a heterogeneidade deste volume, extremamente rico, irá contribuir consideravelmente tanto na formação de jovens graduandos e pós-graduandos, quanto ser atrativo para pro ssionais atuantes nas áreas escolar, técnica e acadêmica aqui abordadas, não eximindo também o leitor “curioso” interessado nas temáticas aqui trazidas.
Article
In this research, the nanostructured alginate (AL) membranes were prepared with natural bioactive compound, Cat's claw (Uncaria tomentosa) extract (UT). UT is broadly used as an anti-inflammatory agent and the effect on the treatment of Rheumatism was proved by many scientists. For this reason, we added this bioactive compound in the process of AL membrane formulation to improve the biological activities. 2-dimentional (2-D) and 3-dimentional (3-D) AL membranes were prepared with and without addition of UT extracts. 3-D AL membranes were prepared using ultrasound with high intensity. The wettability of AL membranes depending on the concentration of AL was studied by measuring contact angle and surface energy. Stabilization agent, poloxamer 407, was used to improve the stability of AL nanoemulsion. The effects of UT in 3-D AL membranes were studied by measuring swelling behavior and contact angle. The surface morphology was measured with scanning electron microscopy (SEM). Comparing to 2-D AL membranes, 3-D AL membranes presented rougher surface due to AL nanoparticles presence. When UT was incorporated in AL membranes, strong antioxidant activity and higher contact angle and swelling ratio were observed than non-UT incorporated AL membranes.
Article
Background The genus Uncaria (Rubiaceae) has several biological properties significant to human health. However, the mechanisms underlying the protective effect of this plant on bone diseases are uncertain. Purpose The present study investigated the role of Uncaria tomentosa extract (UTE) on alveolar bone loss in rats and on osteoclastogenesis in vitro. Materials UTE was characterized by an Acquity UPLC (Waters) system, coupled to an Electrospray Ionization (ESI) interface and Quadrupole/Flight Time (QTOF, Waters) Mass Spectrometry system (MS). The effect of UTE treatment for 11 days on the ligature-induced bone loss was assessed focusing on several aspects: macroscopic and histological analysis of bone loss, neutrophil and osteoclast infiltration, and anabolic effect. The effect of UTE on bone marrow cell differentiation to osteoclasts was assessed in vitro. Results The analysis of UTE by UPLC-ESI-QTOF-MS/MS identified 24 compounds, among pentacyclic or tetracyclic oxindole alkaloids and phenols. The administration of UTE for 11 days on ligature-induced rat attenuated the periodontal attachment loss and alveolar bone resorption. It also diminished neutrophil migration to the gingiva tissue, demonstrated by a lower level of MPO. UTE treatment also decreased the level of RANKL/OPG ratio, the main osteoclast differentiation-related genes, followed by reduced TRAP-positive cell number lining the alveolar bone. Additionally, the level of bone-specific alkaline phosphatase, an anabolic bone marker, was elevated in the plasma of UTE treated rats. Next, we determined a possible direct effect of UTE on osteoclast differentiation in vitro. The incubation of primary osteoclast with UTE decreased RANKL-induced osteoclast differentiation without affecting cell viability. This effect was supported by downregulation of the nuclear factor activated T-cells, cytoplasmic 1 expression, a master regulator of osteoclast differentiation, and other osteoclast-specific activity markers, such as cathepsin K and TRAP. Conclusion UTE exhibited an effective anti-resorptive and anabolic effects, which highlight it as a potential natural product for the treatment of certain osteolytic diseases, such as periodontitis.
Article
Medicinal plants are well-known in affording clinically useful agents, with rich medicinal values by combining with disease targets through various mechanisms. Plant secondary metabolites as lead compounds lay the foundation for the discovery and development of new drugs in disease treatment. Genus Uncaria from Rubiaceae family is a significant plant source of active alkaloids, with anti-hypertensive, sedative, anti-Alzheimer’s disease, anti-drug addiction and anti-inflammatory effects. This review summarizes and discuss the research progress of Uncaria based on alkaloids in the past 15 years, mainly in the past 5 years, including biosynthesis, phytochemistry, pharmacology and structural chemistry. Among, focusing on representative compounds rhynchophylline and isorhynchophylline, the pharmacological activities surrounding the central nervous system and cardiovascular system are described in detail. On the basis of case studies, this article provides a brief overview of the synthesis and analogues of representative compounds types. In summary, this review provides an early basis for further searching for new targets and activities, discussing the mechanisms of pharmacological activity and studying the structure-activity relationships of active molecules.
Chapter
Full-text available
Las enfermedades del sistema respiratorio sin lugar a duda se en-cuentran entre aquellas que presentan la mayor morbilidad a nivel nacional y mundial. Anualmente se gastan ingentes cantidades de dinero en fárma-cos como: antitusígenos, expectorantes, antivirales, antibióticos, antiinfla-matorios y antipiréticos; para mitigar enfermedades y síntomas derivados de afecciones respiratorias ampliamente difundidas entre la población. Los diversos pueblos y nacionalidades que habitan el Ecuador emplean una gran cantidad de plantas medicinales tanto nativas como introducidas como parte de tratamientos alternativos en enfermedades respiratorias. La presente revisión analiza aquellas especies empleadas de forma tradicional, y verifica en las de mayor uso, su sustento científico evaluando la infor-mación química y de actividad biológica que puede ser encontrada en la literatura científica, contribuyendo de esta manera a incrementar el cono-cimiento de los productos naturales que son usados en nuestro país.Las enfermedades del sistema respiratorio inciden con frecuencia en la salud de las personas, siendo extremadamente comunes a lo largo de la vida. La actual pandemia de la Covid-19 muestra la fragilidad de nuestras sociedades ante los patógenos respiratorios, sin embargo, es necesario en-tender que esta no es la primera o la última vez en que la humanidad deberá enfrentarse a una crisis de esta naturaleza [1,2]. A pesar de la compleja situación que vivimos debemos entender que hemos estado expuestos a virus y bacterias con la capacidad de provocar enfermedades respiratorias prácticamente desde nuestra aparición como especie, lo que nos ha llevado a buscar fuentes de curación ya sean de orígenes natural o sintético.El mayor porcentaje de las enfermedades respiratorias como la in-fluenza o las infecciones bacterianas son toleradas por la población sin in-convenientes y solo se manifiestan como peligrosas en personas de avanza-da edad, en el Ecuador sin embargo constituyen la tercera causa de emer-gencia hospitalaria con cerca a un 30 %, siendo más frecuente en niños de hasta 11 años, esto según el boletín del ECEH del 2019, antes del inicio de la pandemia [3]. Un interesante estudio del 2020 realizado en un sector de la ciudad de Quito en medio de la crisis de la Covid-19, muestra que un 88,1 % de la población ha padecido enfermedades respiratorias superiores, un 5,4 % enfermedades respiratorias inferiores y un 4,9 % Covid-19 [4]. Los productos naturales, mucho antes de la aparición de los medica-mentos de síntesis, han sido empleados para tratar enfermedades respiratorias o para mitigar síntomas relacionados a estas como la tos y la inflamación [5-9]. Una gran parte del uso de los productos naturales se basa en el saber ancestral que en el caso del Ecuador al tener varios pueblos y nacionalidades se vuelve fundamental. La otra fortaleza con la que se cuenta es la elevada biodiversidad en los diferentes nichos ecológicos, donde muchas especies vegetales todavía no cuentan con estudios de respaldo en los campos químico y farmacológico.El siguiente trabajo tiene como finalidad un reconocimiento de las plantas usadas en el país para enfermedades y síntomas respiratorios, una revisión de los tipos de tratamientos empleados y finalmente una indaga-ción en literatura científica de aquellas especies de mayor interés farmacéu-tico y bioeconómico.
Article
Full-text available
Background and objective: The safety of plant-derived bioactive compounds has become a global concern. The present study investigated the acute toxicity of aqueous and ethanol extracts of Dialium guineense stem bark using Wistar rats. Methods: Adult male Wistar rats (n = 13) weighing 150-180 g (mean weight = 165 ± 15 g) were used for this study. The aqueous and ethanol extracts of the plant stem bark were obtained using cold maceration method. Lorke method was used to determine oral LD50 of the extracts. Signs of toxicity and possible death of rats were also monitored for twenty-four (24) h. Results: The major signs of toxicity observed within 24 h were: difficulty in breathing, loss of appetite and general weakness. No deaths were recorded in both phases and all the animals in each phytochemical group survived. The oral LD50 of aqueous and ethanol extracts of D. guineense were greater than 5000 mg/kg body weight (bwt). Conclusion: The results of this study suggest that aqueous and ethanol extracts of D. guineense stem bark are not toxic at doses not exceeding 5000 mg/kg bwt.
Chapter
Plants have been utilized for health and medicinal benefits for hundreds of years due to their multiple beneficial attributes such as anticancer, antitumor, antioxidant, antimicrobial, antibacterial, anti-ulcer, anti-arthritic, etc. It has been estimated that there are altogether 250,000 species of higher plants on Earth and among them 35,000–70,000 species are being used to treat various diseases due to the presence of secondary metabolites (alkaloids, flavonoids, steroids, glycosides, saponins, etc.). Cancer is a worldwide leading cause of morbidity and mortality. To cure this at right time, herbal drugs are more beneficial than synthetic drugs, because the synthetic medicines can cause heavy damage to normal cells while destroying the tumor cells. The present work consists of a review of 149 plant families harboring 667 species reported to possess anticancer property. Moreover, other biological properties of the bioactive compounds are also covered. This work is based on reliable data collected from multifarious databases such as CAB abstract, MEDLINE, EMBASE, J GATE, ERIC, Proquest, INMEDPLAN, NATTS, The Plant List, JSTOR, Google Scholar, Springer, Elsevier, and websites such as www.sciencedirect.com, www.jstor.org, www.eflora.org, and www.pfaf.org. The complete data regarding plant names, synonyms, common names, botanical description, medicinal properties, and bioactive compounds present in the plant parts is compiled. In near future, these bioactive compounds can be deployed singly or in combination with routine chemotherapy and radiotherapy to treat various types of cancers, after proper standardization, dose optimization, and stringent clinical trials.
Article
Full-text available
The transcription factor NF-κB is a pivotal regulator of inflammatory responses. While the activation of NF-κB in the arthritic joint has been associated with rheumatoid arthritis (RA), its significance is poorly understood. Here, we examine the role of NF-κB in animal models of RA. We demonstrate that in vitro, NF-κB controlled expression of numerous inflammatory molecules in synoviocytes and protected cells against tumor necrosis factor α (TNFα) and Fas ligand (FasL) cytotoxicity. Similar to that observed in human RA, NF-κB was found to be activated in the synovium of rats with streptococcal cell wall (SCW)-induced arthritis. In vivo suppression of NF-κB by either proteasomal inhibitors or intraarticular adenoviral gene transfer of super-repressor IκBα profoundly enhanced apoptosis in the synovium of rats with SCW- and pristane-induced arthritis. This indicated that the activation of NF-κB protected the cells in the synovium against apoptosis and thus provided the potential link between inflammation and hyperplasia. Intraarticular administration of NF-kB decoys prevented the recurrence of SCW arthritis in treated joints. Unexpectedly, the severity of arthritis also was inhibited significantly in the contralateral, untreated joints, indicating beneficial systemic effects of local suppression of NF-κB. These results establish a mechanism regulating apoptosis in the arthritic joint and indicate the feasibility of therapeutic approaches to RA based on the specific suppression of NF-κB.
Article
Full-text available
In chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease, and psoriasis, several cytokines recruit activated immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state.1 These activated cells produce many other mediators of inflammation. What causes these diseases is still a mystery, but the disease process results from an interplay of genetic and environmental factors. Genes, such as those for atopy in asthma and for HLA antigens in rheumatoid arthritis and inflammatory bowel disease, may determine a patient's susceptibility to the disease and the disease's severity, but environmental factors, often unknown, . . .
Article
Full-text available
Sangre de grado is an Amazonian herbal medicine used to facilitate the healing of gastric ulcers and to treat gastritis, diarrhea, skin lesions, and insect stings. This study was designed to evaluate the gastrointestinal applications. Gastric ulcers were induced in rats by brief serosal exposure of the fundus to acetic acid (80%). Sangre de grado was administered in drinking water at 1:1,000 and 1:10,000 dilutions from the postoperative period to day 7. Guinea pig ileum secretory responses to capsaicin, electrical field stimulation, and the neurokinin-1 (NK-1) agonist [Sar(9),Met(O(2))(11)]substance P were examined in Ussing chambers. Sangre de grado facilitated the healing of experimental gastric ulcer, reducing myeloperoxidase activity, ulcer size, and bacterial content of the ulcer. The expression of proinflammatory genes tumor necrosis factor-alpha, inducible nitric oxide synthase (iNOS), interleukin (IL)-1beta, IL-6, and cyclooxygenase-2 was upregulated by ulcer induction but reduced by sangre de grado treatment, particularly iNOS and IL-6. In Ussing chambers, sangre de grado impaired the secretory response to capsaicin but not to electrical field stimulation or the NK-1 agonist. We conclude that sangre de grado is a potent, cost-effective treatment for gastrointestinal ulcers and distress via antimicrobial, anti-inflammatory, and sensory afferent-dependent actions.
Article
Full-text available
Aim: The purpose of this investigation was to evaluate the ability of cat's claw, an Amazonian medicinal plant, to treat osteoarthritis of the knee, collect safety and tolerance information and compare the antioxidant, and anti-inflammatory actions of Uncaria guianensis and Uncaria tomentosa in vitro. Materials and methods: Forty-five patients with osteoarthritis of the knee were recruited, 30 were treated with freeze-dried U guianensis, and 15 with placebo. Hematological parameters were assessed on entry and exit of the four-week trial. Pain, medical and subject assessment scores and adverse effects were collected at weeks 1, 2 and 4. The antioxidant and anti-inflammatory activity of the cat's claw species was determined by the alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) free radical scavenging method. Inhibition of TNFalpha and prostaglandin E2 (PGE2) production was determined in RAW 264.7 cells by ELISA. Results: Cat's claw had no deleterious effects on blood or liver function or other significant side-effects compared to placebo. Pain associated with activity, medical and patient assessment scores were all significantly reduced, with benefits occurring within the first week of therapy. Knee pain at rest or at night, and knee circumference were not significantly reduced by cat's claw during this brief trial. In vitro tests indicated that U guianensis and U. tomentosa were equivalent at quenching DPPH radicals (EC50, 13.6-21.7 microg/ml) as well as inhibiting TNFalpha production. However, the latter action was registered at much lower concentrations (EC50, 10.2-10.9 ng/ml). Cat's claw (10 microg/ml) had no effect on basal PGE2 production, but reduced LPS-induced PGE2 release (P < 0.05), but at higher concentrations than that required for TNFalpha inhibition. Conclusion: Cat's claw is an effective treatment for osteoarthritis. The species, U guianensis and U tomentosa are equiactive. They are effective antioxidants, but their anti-inflammatory properties may result from their ability to inhibit TNFalpha and to a lesser extent PGE2 production.
Article
Full-text available
The precise role of the transcription factor nuclear factor kappa B (NF- kappaB) in the regulation of cell survival and cell death is still unresolved and may depend on cell type and position in the cell cycle. The aim of this study was to determine if three pharmacologic inhibitors of NF-kappaB, pyrrolidine dithiocarbamate, N-tosyl-L-lysl chloromethyl ketone and calpain I inhibitor, induce apoptosis in a murine macrophage cell line (RAW 264.7) at doses similar to those required for NF-kappaB inhibition. We found that each of the three inhibitors resulted in a dose- and time-dependent increase in morphologic indices of apoptosis in unstimulated, LPS-stimulated and TNF-stimulated cells. Lethal doses were consistent with those required for NF- kappaB inhibition. We conclude that nuclear NF-kappaB activation may represent an important survival mechanism in macrophages.
Article
Objective To explore the signaling pathways by which the proinflammatory cytokine interleukin‐17 (IL‐17) may contribute to cartilage catabolism in osteoarthritis (OA) by inducing inducible nitric oxide synthase (iNOS) expression in chondrocytes. Methods We examined the IL‐17–induced NO production in human OA chondrocytes, in combination with the proinflammatory cytokines IL‐1β, tumor necrosis factor α (TNFα), and leukemia inhibitory factor (LIF); the antiinflammatory cytokines IL‐4, IL‐10, and IL‐13; and IL‐1 receptor antagonist (IL‐1Ra). Further, we explored the major intracellular signaling pathways through which IL‐17 induced iNOS expression and NO production. Results Treatment with IL‐17 induced a dose‐dependent increase in the level of NO. When IL‐17 was combined with the above factors, it resulted in a synergistic effect with TNFα, an additive effect with LIF, and no further effect than when used alone with IL‐1β. IL‐4, IL‐10, IL‐13, and IL‐1Ra had no true effect on IL‐17–induced NO production. The cAMP mimetics, 3‐isobutyl‐1‐methyl xanthine plus forskolin, completely blocked IL‐17–induced NO production. KT‐5720, genistein, and Calphostin C, inhibitors of protein kinase A (PKA), tyrosine kinase, and protein kinase C, respectively, reduced the IL‐17–induced NO production by 72%, 56%, and 42%, respectively. Within minutes, IL‐17 induced the phosphorylation of mitogen‐activated protein kinase kinase‐1/2 (MEK‐1/2), ‐3/6 (MKK‐3/6), p44/42, p38, and inhibitor of nuclear factor κB (IκB)‐α, as well as the activation of mitogen‐activated protein kinase–activated protein kinase‐1 and ‐2 (MAPKAPK‐1 and ‐2). Interestingly, IL‐17 induced phosphorylation of the stress‐activated protein kinase/Jun N‐terminal kinase (SAPK/JNK) (p54/46) only when PKA was inhibited. Specific protein kinase inhibitors for MEK‐1/2 (PD98059), p38 (SB202190), and nuclear factor κB (NF‐κB) (pyrrolidine dithiocarbamate) each markedly decreased the IL‐17–increased iNOS level and NO production. Inhibiting MAPK, including MEK‐1/2 and p38, had no effect on the IL‐17–induced activation of IκB‐α, but reversed the IL‐17 activation of MAPKAPK‐1 and ‐2, respectively. Conclusion These findings show that the stimulation of NO production by IL‐17 is mediated mainly by a complex activation of kinases, especially PKA, NF‐κB, and MAPK. NF‐κB appears to require MAPK activation, with downstream activation of MAPKAPK probably acting as a transactivating factor, to induce iNOS expression.
Article
Sixteen plants of Uncaria tomentosa were investigated for their alkaloid content and the alkaloid distribution in various parts of the plant was examined. Two chemical types were identified. Seventeen alkaloids were detected and a seasonal variation in the alkaloid content was observed.
Article
Different extracts of U. tomentosa were tested in vitro for their antioxidant activity utilizing tert -butyl-hydroperoxide-initiated chemiluminescence in rat liver homogenates. Methanol fractions of both stem-bark and roots were capable of exerting antioxidant activity by this technique. The presence of different concentrations of bark and root methanol extracts also prevented TBARS production and free radical-mediated DNA-sugar damage. © 1997 John Wiley & Sons, Ltd.
Article
Objective To explore the signaling pathways by which the proinflammatory cytokine interleukin-17 (IL-17) may contribute to cartilage catabolism in osteoarthritis (OA) by inducing inducible nitric oxide synthase (iNOS) expression in chondrocytes.Methods We examined the IL-17–induced NO production in human OA chondrocytes, in combination with the proinflammatory cytokines IL-1β, tumor necrosis factor α (TNFα), and leukemia inhibitory factor (LIF); the antiinflammatory cytokines IL-4, IL-10, and IL-13; and IL-1 receptor antagonist (IL-1Ra). Further, we explored the major intracellular signaling pathways through which IL-17 induced iNOS expression and NO production.ResultsTreatment with IL-17 induced a dose-dependent increase in the level of NO. When IL-17 was combined with the above factors, it resulted in a synergistic effect with TNFα, an additive effect with LIF, and no further effect than when used alone with IL-1β. IL-4, IL-10, IL-13, and IL-1Ra had no true effect on IL-17–induced NO production. The cAMP mimetics, 3-isobutyl-1-methyl xanthine plus forskolin, completely blocked IL-17–induced NO production. KT-5720, genistein, and Calphostin C, inhibitors of protein kinase A (PKA), tyrosine kinase, and protein kinase C, respectively, reduced the IL-17–induced NO production by 72%, 56%, and 42%, respectively. Within minutes, IL-17 induced the phosphorylation of mitogen-activated protein kinase kinase-1/2 (MEK-1/2), -3/6 (MKK-3/6), p44/42, p38, and inhibitor of nuclear factor κB (IκB)-α, as well as the activation of mitogen-activated protein kinase–activated protein kinase-1 and -2 (MAPKAPK-1 and -2). Interestingly, IL-17 induced phosphorylation of the stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) (p54/46) only when PKA was inhibited. Specific protein kinase inhibitors for MEK-1/2 (PD98059), p38 (SB202190), and nuclear factor κB (NF-κB) (pyrrolidine dithiocarbamate) each markedly decreased the IL-17–increased iNOS level and NO production. Inhibiting MAPK, including MEK-1/2 and p38, had no effect on the IL-17–induced activation of IκB-α, but reversed the IL-17 activation of MAPKAPK-1 and -2, respectively.Conclusion These findings show that the stimulation of NO production by IL-17 is mediated mainly by a complex activation of kinases, especially PKA, NF-κB, and MAPK. NF-κB appears to require MAPK activation, with downstream activation of MAPKAPK probably acting as a transactivating factor, to induce iNOS expression.
Article
The main oxindole alkaloids from the root bark ofUncaria tomentosa were separated by reversed phase HPLC with an acetonitrile/methanol/phosphate buffer solvent gradient. UV detection was carried out at 245 nm. The chromatographic parameters for the separation of the alkaloids were optimized by studying the impact of the pH value of the mobile phase and the column temperature on the separation efficiency of the analytical system. The best separation was achieved with a mobile phase pH of 6.6 and a column temperature of 15C. The method developed is suitable for the qualitative characterisation and quantitative determination of oxindole alkaloids in crudeUncaria tomentosa extracts and phytopharmaceuticals.
Article
The ability of BW755C to reduce ethanol- or indomethacin-induced gastric damage and the role of prostanoids in the mechanism of this action were examined in the rat. BW755C (1–100 mg/kg) caused a dose-related reduction in the amount of damage produced by oral administration of 40% ethanol in 100 mM HCl. At the doses tested, BW755C had no significant effect on mucosal 6-keto-prostaglandin F1α synthesis, but did cause a dose-dependent reduction in thromboxane B2 synthesis. The effect on thromboxane synthesis may be due to a selective inhibition of platelet cyclo-oxygenase by BW755C. The higher doses of BW755C (50 and 100 mg/kg) caused a significant increase in the volume of fluid present in the gastric lumen, which may contribute to the protective action of the drug against ethanol-induced damage. Oral administration of BW755C (50 mg/kg) significantly reduced the extent of gastric damage caused by subcutaneous injection of indomethacin (20 mg/kg) indicating that it is unlikely that the protective action of BW755C is mediated by endogenous prostanoids. The mechanism of the protective actions of BW755C may be related to its reported ability to inhibit lipoxygenase or to its actions as a free-radical scavenger.
Article
From the bark of Uncaria guianensis, two new quinovic acid glycosides, quinovic acid 3 beta-O-beta-D-quinovopyranoside and quinovic acid 3 beta-O-beta-D-fucopyranosyl-(27----1)-beta-D-glucopyranosylester, have been isolated, in addition to known quinovic acid 3 beta-O-[beta-D-glucopyranosyl-(1----3)-beta-D-fucopyranosyl]-(27----1)- beta-D-glucopyranosylester and quinovic acid 3 beta-O-beta-D-fucopyranoside. Their structures were elucidated by spectral and chemical studies.
Article
Bioassay-directed fractionation of the anti-inflammatory extracts of Uncaria tomentosa, using the carrageenan-induced edema in rat paw, has led to the isolation of a new quinovic acid glycoside 7 as one of the active principles. Furthermore, a new triterpene 8 was isolated as its methyl ester. The structures were elucidated by spectral and chemical studies.
Article
Three novel polyhydroxylated triterpenes have been isolated from Uncaria tomentosa. Their structures were established as 1, 2, and 3 by detailed spectral studies including 1H-13C correlations via long range couplings using the INAPT pulse sequence, nOeds, and 2D 1H-13C direct chemical shift correlation (HETCOR) nmr techniques.
Article
A reinvestigation of the bark of Uncaria tomentosa afforded, in addition to the major quinovic acid glycosides 1-3, three further glycosides 4-6. The structures were elucidated by spectral and chemical studies. Furthermore, a series of antiviral tests were performed on all these glycosides and on the related glycosides 7-9, previously isolated from Guettarda platypoda.
Article
The investigation on steroidic fraction of Uncaria tomentosa, commonly called Una de gato, showed the presence of beta-sitosterol (60%), stigmasterol, and campesterol. The percentage of sterols have been carried out by GLC. The spectroscopic data 1H-NMR and MS of the three compounds are also reported, with the beta-sitosterol as the main sterol. Preliminary pharmacological investigations prove a moderate antiinflammatory activity.
Article
Hydroxyl radicals, generated by reaction of an iron-EDTA complex with H2O2 in the presence of ascorbic acid, attack deoxyribose to form products that, upon heating with thiobarbituric acid at low pH, yield a pink chromogen. Added hydroxyl radical "scavengers" compete with deoxyribose for the hydroxyl radicals produced and diminish chromogen formation. A rate constant for reaction of the scavenger with hydroxyl radical can be deduced from the inhibition of color formation. For a wide range of compounds, rate constants obtained in this way are similar to those determined by pulse radiolysis. It is suggested that the deoxyribose assay is a simple and cheap alternative to pulse radiolysis for determination of rate constants for reaction of most biological molecules with hydroxyl radicals. Rate constants for reactions of ATP, ADP, and Good's buffers with hydroxyl radicals have been determined by this method.
Article
Studies on mice deficient in nuclear factor kappa B (NF-kappaB) subunits have shown that this transcription factor is important for lymphocyte responses to antigens and cytokine-inducible gene expression. In particular, the RelA (p65) subunit is required for induction of tumor necrosis factor-alpha (TNF-alpha)-dependent genes. Treatment of RelA-deficient (RelA-/-) mouse fibroblasts and macrophages with TNF-alpha resulted in a significant reduction in viability, whereas RelA+/+ cells were unaffected. Cytotoxicity to both cell types was mediated by TNF receptor 1. Reintroduction of RelA into RelA-/- fibroblasts resulted in enhanced survival, demonstrating that the presence of RelA is required for protection from TNF-alpha. These results have implications for the treatment of inflammatory and proliferative diseases.
Article
It is becoming increasingly apparent that the chronic gut inflammation observed in the idiopathic inflammatory bowel diseases (e.g. ulcerative colitis, Crohn's disease) is associated with enhanced production of leukocyte-derived oxidants. Oxidants such as hydrogen peroxide are known to activate certain transcription factors such as nuclear transcription factor kappa beta. Nuclear transcription factor kB (NF-kappa B) is a ubiquitous transcription factor and pleiotropic regulator of numerous genes involved in the immune and inflammatory responses. This transcription factor is activated via the selective phosphorylation, ubiquination and degradation of its inhibitor protein I-kB thereby allowing translocation of NF-kappa B into the nucleus where it upregulates the transcription of a variety of adhesion molecules (e.g. ICAM-1, VCAM-1), cytokines (TNF, IL-1, IL-6) and enzymes (iNOS). The proteolytic degradation of the post-translationally modified I-kappa B is known to be mediated by the 26S proteasome complex. Based upon work from our laboratory, we propose that inhibition of NF-kappa B activation produces significant anti inflammatory activity which may be mediated by the inhibition of transcription of certain pro-inflammatory mediators and adhesion molecules.
Article
To quantify the relationship between fruit and vegetable consumption and the incidence of ischaemic heart disease. A meta-analysis of cohort studies of the relationship between ischaemic heart disease and markers of fruit and vegetable consumption, namely dietary intake of fruit, vegetables, carotenoids, vitamin C, fruit fibre and vegetable fibre, and serum concentration of carotenoids and vitamin C, adjusted for other risk factors. Risk of ischaemic heart disease at the 90th centile of consumption relative to that at the 10th, equivalent to about a four-fold difference in fruit consumption and a doubling of vegetable consumption. The association with ischaemic heart disease was of similar magnitude for all six dietary markers of fruit and vegetable consumption. The median of the six estimates was that risk was 15% (range 12-19%) lower at the 90th centile of consumption than at the 10th. The estimates were generally adjusted for the possible confounding effect of other heart disease risk factors. The serum studies of vitamin C were consistent with this; those of carotenoids suggested a larger difference (43%) but were not adjusted for the important confounding effect of smoking. The substances in fruit and vegetables responsible for the protective effect on heart disease are uncertain but the effect is commensurate with the estimated protective effects of the potassium and folate in fruit and vegetables. Beta-carotene or vitamin E are not likely to be important because randomised trials of these vitamins in large doses have shown no reduction in heart disease mortality. The risk of ischaemic heart disease is about 15% lower at the 90th than the 1Oth centile of fruit and vegetable consumption.
Article
Immunohistochemistry has been critical in determining the tissue localization of inducible nitric oxide synthase (iNOS). However, this technique suffers from nonspecific staining which may lead to false-positive results and the failure of antisera to recognize iNOS from different species. We developed a technique to determine the localization of iNOS mRNA, as opposed to protein, in tissue sections using an in situ RT-PCR (IS RT-PCR) technique. Sections of inflamed gastrointestinal mucosa were used because they were known to be positive for iNOS. The IS RT-PCR technique localized iNOS mRNA to the same sites as immunoreactive iNOS in human gastritis associated with Helicobacter pylori infection, Crohn's disease, and experimental inflammatory bowel disease induced by the hapten TNBS, in rat colon and in guinea pig ileum. The detection of mRNA had an excellent signal-to-noise ratio. Preservation of tissue morphology was poorer than that with immunohistochemistry due the cycles of heating required in the PCR process. This method could be very useful in detecting iNOS gene expression in situations of excessive nonspecific staining with immunohistochemistry or of failure of antibodies to react because of species differences. This technique is also readily applicable to detect RNA and DNA markers of other disease processes.
Article
Although previous studies indicate that prevention of tumour necrosis factor alpha (TNFalpha) release protects against NSAID-induced gastric mucosal injury, intracellular pathways by which aspirin causes TNFalpha release are unknown. TNFalpha is synthesized as a precursor which is proteolytically cleaved by a specific converting enzyme, TACE, to release the mature cytokine. TACE inhibitors prevent TNFalpha release and protect against TNFalpha-mediated disease. To investigate: (i) molecular events that regulate TNFalpha secretion in response to aspirin in vivo and in vitro; (ii) whether TNFalpha secretion inhibitors prevent aspirin-induced TNFalpha release and protect against gastric mucosal damage; and (iii) whether TNFalpha exerts a direct cytotoxic effect on gastric epithelial cells. In vitro studies were carried out on mouse macrophages and rat gastric mucosal cells. Gastric mucosal damage was induced in rats by oral administration of 300 mg/kg aspirin. TNFalpha cytotoxicity on gastric mucosal cells was examined by treating rats with lipopolysaccharide to release TNFalpha or by incubating dispersed gastric mucosal cells with increasing concentrations of TNFalpha. Aspirin increases intracellular calcium (Ca2+) levels and causes a time and concentration dependent increase in macrophage TNFalpha mRNA accumulation and cytokine release. Agents that cause Ca2+ mobilization with a receptor-independent mechanism, such as ionomycin and thapsigargin, stimulate TNFalpha release. Incubating the macrophages in a Ca2+ free medium inhibited TNFalpha secretion. Agents that prevent TNFalpha mRNA transcription, e.g. lisophylline, PGE2, interleukin-10 and 8-BrcAMP, or TACE inhibitors, e.g. EDTA, TAPI-2 and BB-3103, inhibit TNFalpha release and protect rats against gastric mucosal injury induced by oral administration of aspirin. TNFalpha exerts a direct cytotoxic effect on gastric epithelial cells as demonstrated by the reduced viability observed in gastric mucosal cells prepared from rats treated with lipopolysaccharide, or directly incubated with increasing concentrations of TNFalpha. (i) Aspirin directly stimulates TNFalpha gene transcription; (ii) TACE inhibitors protect against aspirin-induced gastric mucosal injury; and (iii) TNFalpha exerts a direct cytotoxic effect on gastric epithelial cells.
Article
Growth inhibitory activities of novel water extracts of Uncaria tomentosa (C-Med-100) were examined in vitro using two human leukemic cell lines (K562 and HL60) and one human EBV-transformed B lymphoma cell line (Raji). The proliferative capacities of HL60 and Raji cells were strongly suppressed in the presence of the C-Med-100 while K562 was more resistant to the inhibition. Furthermore, the antiproliferative effect was confirmed using the clonogenic assay, which showed a very close correlation between C-Med-100 concentration and the surviving fraction. The suppressive effect of Uncaria tomentosa extracts on tumor cell growth appears to be mediated through induction of apoptosis which was demonstrated by characteristic morphological changes, internucleosomal DNA fragmentation after agarose gel electrophoresis and DNA fragmentation quantification. C-Med-100 induced a delayed type of apoptosis becoming most dose-dependently prominent after 48 hours of exposure. Both DNA single and double strand breaks were increased 24 hours after C-Med-100 treatment, which suggested a well-established linkage between the DNA damage and apoptosis. The induction of DNA strand breaks coupled to apoptosis may explain the growth inhibition of the tumor cells by Uncaria tomentosa extracts. These results provide the first direct evidence for the antitumor properties of Uncaria tomentosa extracts to be via a mechanism of selective induction of apoptosis.
Article
Uncaria tomentosa is a vine commonly known as cat's claw or 'uña de gato' (UG) and is used in traditional Peruvian medicine for the treatment of a wide range of health problems, particularly digestive complaints and arthritis. The aim of this study was to determine the proposed anti-inflammatory properties of cat's claw. Specifically: (i) does a bark extract of cat's claw protect against oxidant-induced stress in vitro, and (ii) to determine if UG modifies transcriptionally regulated events. Cell death was determined in two cell lines, RAW 264.7 and HT29 in response to peroxynitrite (PN, 300 microM). Gene expression of inducible nitric oxide synthase (iNOS) in HT29 cells, direct effects on nitric oxide and peroxynitrite levels, and activation of NF-kappaB in RAW 264.7 cells as influenced by UG were assessed. Chronic intestinal inflammation was induced in rats with indomethacin (7.5 mg/kg), with UG administered orally in the drinking water (5 mg/mL). The administration of UG (100 microg/mL) attenuated (P < 0.05) peroxynitrite-induced apoptosis in HT29 (epithelial) and RAW 264.7 cells (macrophage). Cat's claw inhibited lipopolysaccharide-induced iNOS gene expression, nitrite formation, cell death and inhibited the activation of NF-kappaB. Cat's claw markedly attenuated indomethacin-enteritis as evident by reduced myeloperoxidase activity, morphometric damage and liver metallothionein expression. Cat's claw protects cells against oxidative stress and negated the activation of NF-kappaB. These studies provide a mechanistic evidence for the widely held belief that cat's claw is an effective anti-inflammatory agent.
Article
In the present study we show that pentacyclic but not tetracyclic oxindole alkaloids from Uncoria tomentosa (Willd.) DC. (Rubiaceae) induced EA.hy926 endothelial cells to release some yet to be determined factor(s) into the supernatant; this factor was shown to significantly enhance proliferation of normal human resting or weakly activated B and T lymphocytes. In contrast, proliferation of normal human lymphoblasts and of both the human lymphoblastoid B cell line Raji and the human lymphoblastoid T cell line Jurkat was inhibited significantly while cell viability was not affected. Tetracyclic oxindole alkaloids dose-dependently reduce the activity of pentacyclic oxindole alkaloids on human endothelial cells.
Article
The medicinal system of the Asháninka Indians in Perú is portrayed. Three categories of medical disorders and healers are recognized. A human is viewed to consist of a physical and a spiritual being who communicate with each other by means of a regulating element. The significance of Uncaria tomentosa (Willd.) DC. (Rubiaceae), locally known as unã de gato, in traditional medicine is emphasized by its exclusive use by priests to influence this regulation. Pharmacological and toxicological results obtained with extracts or isolated compounds are summarized. Pentacyclic oxindole alkaloids stimulate endothelial cells in vitro to produce a lymphocyte-proliferation-regulating factor. Tetracyclic oxindole alkaloids act as antagonists. A significant normalization of lymphocyte percentage was observed in vivo although total leucocyte numbers did not change.