Uncaria tomentosa (or cat's claw) as a powerful “plaque” and. An official website of the United States government El. gov means that it is official. Federal government websites often end in.
government or. thousand. Before sharing sensitive information, make sure you're on a federal government site. In the next series of studies, assay-guided fractionation and sophisticated structure elucidation techniques identified specific polyphenolic ingredients and proanthocyanidins.
in the cat's claw of PTI-00703 (i.e., Uncaria tomentosa (from a specific Peruvian source) which has the natural ability to reduce and inhibit both beta-amyloid protein “plaques” and tau protein knots, the two characteristics of brain aging and the pathological characteristics of Alzheimer's disease. Cat's claw in PTI-00703 is a potent inhibitor of Abeta 1-40 fibril formation. A) Cat's claw in PTI-00703 inhibited, depending on the dose, the formation of Abeta 1—40 fibrils, as evaluated by fluorometry with thioflavin T. Fractions f a o) were evaluated in several different in vitro tests.
The tests included the use of thioflavin T fluorometry, Congo red staining tests, and negative EM staining. In most experiments, the individual fractions isolated from PTI-777 were directly compared to cat's claw (PTI-00703), PTI-777 and the main oxindolic alkaloids isolated from Uncaria tomentosa and which were believed to have significant bioactivity, as described in two U.S. patents 36,37 (fig. The preparatory HPLC work for PTI-777 described here resulted in between 11 and 13 major active fractions soluble in water, each containing primarily a major compound.
Structural and compositional studies required that the main individual compounds in each fraction be purified to homogeneity in sufficient quantity to perform NMR and other spectroscopy studies (about 30 to 50 mg per composite). Although each of the PTI-777 fractions showed significant activity in vitro tests, fractions f, j, h1, h2, k1 and k2 were initially selected for initial final purification based on their initial purity determined by analytical HPLC, and the amount of material available. These fractions were passed through the preparatory HPLC column until they were considered pure. Various methods were used to isolate and identify the main compound of fraction f of PTI-777: HPLC, mass spectroscopy, NMR spectroscopy (1H NMR and 13C NMR), correlation spectroscopy (COSY) and ultraviolet (UV) spectroscopy. As shown in the supplementary material, Fig.
The S1a, S1b, PTI-777 fraction of the compound was identified as chlorogenic acid (C16H18O9; PM 354.3) with a structure such as that shown in Fig. Fraction j was the second material that was purified in an amount sufficient for structural elucidation work. After the isolation and purification of compound j from PTI-777, mass spectroscopy, NMR spectroscopy, correlation spectroscopy (COSY) and UV spectroscopy were used for the fraction j compound and its derivative of pentaacetate. The compound S2a-S2w, fraction j of PTI-777 was identified as epicatechin (C15H14O6; MW 290.2), with a structure such as that shown in Fig.
The h2 fraction was the third material that was purified in sufficient quantity to carry out structural elucidation work. After the isolation and purification of compound h2 from PTI-777, HPLC, electroscopy by electrospray with -ve ions, NMR spectroscopy (1H NMR and 13C NMR), correlation spectroscopy (COSY) and ultraviolet (UV) spectroscopy were used. The main component of the h fraction of the PTI-777 extract was also an important component of Uncaria tomentosa (cat's claw), responsible for the inhibitory and disaggregation activity of the proteins Aß (plaque) and tau (tangle) (see Fig. The compound S3A—S3M, fraction h2 of PTI-777, was identified as epicatechin-4β-8-epicatechin, also known as proanthocyanidin B2 (C30H26O12; MW 57), with a structure such as that shown in Fig. Fraction h1 was the fourth material that was purified in sufficient quantity to carry out structural elucidation work.
After the isolation and purification of compound h1 from PTI-777, by HPLC, mass spectroscopy by electronebulization with -ve ions. NMR spectroscopy (1H NMR and 13C NMR), correlation spectroscopy (COSY), constant time spectroscopy with inverse detection gradient with scaled accordion (CIGAR) and ultraviolet (UV) spectroscopy were used. The compound S4a—S4j, fraction h1 of PTI-777 was identified as catechin-4α-8-epicatechin (fig. Cortexal levels) of soluble and insoluble Abeta42 and Abet40 in TASD-41 APP transgenic mice younger than 4 months were significantly (p) Reduced brain plaque burden in younger (a—h) and older (i-j) TASD-41 APP transgenic mice due to proanthocyanidin B2 (compound h.
a—h) Reduction in brain load of Ab Β 1—42 and AΒ 1—40 for proanthocyanidin B2 (i, e. Compound h in younger APP transgenic mice (4 months old at baseline; 7 months old at sacrifice).A) Proanthocyanidin B2 caused a significant (p) As shown in Fig. In this last study, animals treated with proanthocyanidin B2 showed significant immunostaining (p). Both GFAP immunostaining (for astrocytes) and MHC-II immunostaining (for microglia) in APP transgenic mice treated with proanthocyanidin B2 were quantified using an image analysis program.
Quantitative image analysis indicated that compound h2 caused a significant reduction (p) of proanthocyanidin B2 in plaque load Abeta and plaque number in younger people (i.e., p.Importance of specific hydroxyl groups in polyphenolic compounds reported as inhibitors of amyloid Abeta fibrillogenesis. A) Curcumin has a hydroxyl group (OH) next to a methoxy group in its aromatic rings. B) Resveratrol has no adjacent hydroxyl groups. C) Epicatechin has adjacent hydroxyl groups in one of their aromatic rings.
D) Catechin also has adjacent hydroxyl groups on one of its aromatic rings. E) Epicatechin gallate (ECG) has aromatic rings with two and three adjacent hydroxyl groups on one of its aromatic rings. F) Epigallocatechin gallate (EGCG) has two aromatic rings, each containing three adjacent hydroxyl groups. Porat et al, 88, suggested that the mechanism of inhibiting the formation of amyloid fibrils by small polyphenolic compounds requires a) a specific structural conformation necessary for a specific interaction between beta-sheets and the stabilization of the inhibitor-protein complex, and b) an aromatic interaction between the phenolic compound of the inhibitor molecule and aromatic residues (such as phenylalanine in residues 4, 19 and 20 of Ab 1-4) in the amyloidogenic sequence that can direct and inhibit the amyloidogenic nucleus and facilitates bonding interaction, but it also interferes with the fibril mounting. We postulate that PTI-00703 cat's claw is a superior natural product that is effective against both Abeta plaques and tau protein tangles, especially compared to other polyphenols that lack a catechol group (i.e., two adjacent hydroxyl groups in an aromatic ring), such as resveratrol and curcumin (fig.
It should also be noted that Uncaria tomentosa (cat's claw) has a multitude of polyphenolic components, each of which contains aromatic rings with two adjacent hydroxyl groups. This includes chlorogenic acid, epicatechin, proanthocyanidins B2, B4, and C1, and epicatechin tetramers, all identified in the present research. Therefore, it is posited that the cat's claw in PTI-00703 has superior inhibitory and reducing activity on both “plates” and tangles because most of its main components contain aromatic rings containing dihydroxyl groups. In our hands, PTI-00703 cat's claw can significantly reduce tumor necrosis factor (TNF-α) and interleukin 1, two important inflammatory cytokines (Snow et al.
In fact, the reduction of cerebral astrocytosis (fig.) To evaluate the purity of the main individual components of the PTI-777, analytical HPLC with a diode array detector (Agilent series) was used 1100). In addition to observing a single peak using a UV chromatogram, the allowed diode array detection is to ensure that the back end of each peak has the same (superimposable) spectra as at the center and front edge of the peaks, indicating purity. The collected compounds were then analyzed using mass spectroscopy and nuclear magnetic resonance (NMR) spectroscopy (see supplementary information). Various methods were applied to identify the main compounds of the major fractions of PTI-777 (i.e., the inhibitory components of amyloid beta present in cat's claw).These latter studies included the use of HPLC, electrospray mass spectroscopy with -ve ions (relative intensity of the molecular ion expressed as a percentage), Fourier transfer mass spectroscopy, ultraviolet spectroscopy, 1H NMR, 13C NMR, mass spectroscopy with time of flight by electrospray ionization (ESI-TOF), mass spectroscopy initiated by electron impact (EI) and mass spectroscopy with rapid atomic bombardment (FAB) spectroscopy of homonuclear correlation (COSY), correlation spectroscopy of multiple heteronuclear bonds rescaled in accordion with constant time inverse detection gradient (CIGAR) and heteronuclear correlation spectroscopy (HETCOR).
All solvents were distilled before use and removed by rotary evaporation at temperatures up to 20°C. Octadecyl-functionalized silica gel (C1) was used for reverse-phase ultrafast chromatography (RP), and silica gel 60, 200 to 400, 40 to 63 µm was used for Merck silica gel ultrafast chromatography. Thin layer chromatography was carried out using Merck DC-Plastikfolien Kieselgel 60 F254, first visualized with a UV lamp and then immersed in a 5% aqueous solution of ferric chloride. Optical rotations were measured on a Perkin-Elmer 241 polarimeter. At appropriate times, the mice were euthanized under deep anaesthesia and exsanguination.
The brain was carefully removed, divided in two along the midline and half of the brains were instantly frozen and the other half were immersed in 20 ml of fresh 4% paraformaldehyde (PFA) in PBS at 4°C. The next morning, PFA was replaced by PBS and the brains were stored at 4°C before the vibratome was cut (Leica Biosystems).The antibodies used included 6E10 for amyloid Abeta plaques; glial fibrillary acid protein (GFAP) for astrocytes (Dako) and MHC-II (Dako) for microglia. All murine studies involving the use of stereotactic devices, the use of osmotic pumps, the peripheral administration of PTI-777 and its components, proanthocyanidin B2 (compound h2) and behavioral tests were approved by the Institutional Animal Care and Use Committee (IACUC) of the University of California at San Diego (EM Laboratories) and were conducted in accordance with approved animal care and use protocols (ACUP). All rodent and murine studies using radiolabeled PTI-777 to penetrate the blood-brain barrier were approved by the Institutional Animal Care and Use Committee (IAUCAC) of the Pennington Biomedical Research Center at Louisiana State University, Baton Rouge, LO (AK and WP laboratories).
Own capital at Cognitive Clarity Inc. He is a paid employee of Cognitive Clarity Inc. Cummings, Thomas Lake and Lesley Larsen contributed equally to the National Library of Medicine 8600 Rockville Pike Bethesda, MD 20894 Web Policies FOIA HHS Vulnerability Disclosure Help Accessibility Careers. Uncaria tomentosa, which has chemical components similar to those of Uncaria rhynchophylla, has been reported to alleviate cognitive deficiencies in animal models with Alzheimer's disease (AD).
This study aimed to compare the chemical components and the anti-AD effect of ethanolic extracts from U.Donepezil hydrochloride was purchased from Sigma-Aldrich (St. Streptozotocin (STZ, ≥ 98% purity) was purchased from Santa Cruz Biotechnology (Dallas, USA). UU.). Ethanol was obtained from DAEJUNG Chemicals (Gyeonggi-do, Korea).
Methanol (HPLC grade) was purchased from Duksan Pure Chemicals (Gyeonggi-do), Korea). Triethylamine (HPLC grade) was purchased from Scharlau (Barcelona, Spain). Standard substances (rincophyllin, isorhincophyllin, corinoxein and isocorinoxein, with a purity of ≥ 98%) were purchased from Chengdu Mansite Pharmaceuetical Co. All other chemicals and reagents used were of analytical quality.
The experimental apparatus consisted of a circular pool (150 cm in diameter, 45 cm in height), filled to a depth of 30 cm with water at 24 °C. The group was conceptually divided into four equal quadrants for the collection of descriptive data. A circular escape platform (10 cm in diameter) was submerged 1 cm below the surface of the water at the midpoint of a quadrant (objective quadrant). Different geometric signs were placed around the pool, which can be used by experimental animals to determine the location of the platform.
Rats were trained to find the hidden platform with three attempts per day for four consecutive days. Each rat was placed in the water in front of the pool wall from different release positions. The escape latency for climbing onto the platform of each trail was recorded. The maximum test time was 60 s.
If a rat could not find the platform in 60 s, it was manually guided to the platform and left to remain there for 10 s (except 30 s on the first day), and the escape latency was recorded at 60 s.The probe test was performed without the hidden platform 24 hours after the last day of training. Rats were allowed to swim freely in the water for 60 s. A computerized video tracking system (SuperMaze V2.0 software) from Shanghai Xinruan Information Technology Co. Twenty-four hours after the MWM test, the rats were euthanized under deep anaesthesia.
The rats were then perfused transcardially with ice-cold (0.9%) saline solution until the fluid exiting the right atrium became completely clear to remove peripheral blood from the CNS vasculature. Hippocampal tissues were rapidly isolated from the brain on ice and stored at -80°C until use. To evaluate the effects of UTE and URE on oxidative stress in the STZ-induced Alzheimer's model, the activity levels of SOD, CAT, MDA and GPx were evaluated. For these biochemical analyses, brain tissues were homogenized and measured with SOD, CAT, MDA and GPx test kits (Cat.
All samples were measured in duplicate. All data were presented as means ± standard deviation (mean ± SD) and all statistical analyses were performed with the SPSS 20.0 software (SPSS Inc, Chicago, IL, USA). The differences between the groups in terms of escape latency in the MWM training task were analyzed using a bidirectional analysis of variance (ANOVA) with repeated measures, taking into account the treatment and the training day. The other differences between several groups were analyzed using a one-way ANOVA and the differences between the two groups were analyzed.
using the t test. A difference was considered statistically significant when the MWM p-test was used to determine learning and spatial memory in the STZ-induced AD rat model. The rats in the STZ+ vehicle group had a longer escape latency to find the hidden platform than those in the Sham group during training days (day 2, p). The protein expressions of total Tau (Tau-46) and Tau- in the STZ+ vehicle group increased significantly compared to the Sham group (p).
Compared to the Sham group, there was a significant increase in the levels of IL-1beta, IL-6 and TNF-α in the STZ+ vehicle group (p). To evaluate the antioxidant potential of UTE and URE in rats with STZ-induced AD, the levels of the oxidative damage marker (MDA), the antioxidant enzyme The activities (SOD, CAT and GPx) and protein expression of HO-1 were measured. SOD activity significantly decreased in the STZ + vehicle group (p) The STZ+ vehicle group had markedly lower CAT activity than the Sham group (p) GPx activity was significantly reduced in the STZ control group (p). Compared to the Sham group, the level of MDA, a marker of oxidative damage, was markedly accentuated in the STZ control group (p) The antioxidant effects of UTE and URE STZ were further determined by analyzing the protein expression of HO-1 in rats with AD induced by Z.
There was no difference in HO-1 expression between the Sham group and the STZ control group. Treatment with UTE and URE significantly up-regulated the expression of the HO-1 protein in the brain of rats treated with STZ (p). The effects of UTE and URE on the nuclear translocation of Nrf2 were evaluated by analyzing the expression of the Nrf2 protein and its upstream target, Keap1, in rats with STZ-induced AD. The western blot results showed that, compared to the Sham group, there was a reduction in nuclear Nrf2 protein expression in the STZ control group (p) Uncaria rhynchophylla extract PubMed Google Scholar CAS PubMed PubMed Central PubMed Article PubMed Central Google Scholar PubMed Article Central CAS Google Scholar CAS Google Scholar This work was supported by a grant from Li Dak Sum Yip Yio Chin I+D Center for Chinese Medicine at the Chinese University of Hong Kong. The School of Chinese Medicine of the Faculty of Medicine of the Chinese University of Hong Kong, Shatin, N, T.
QQX conducted the animal studies and collected the experimental data. ZH and SPI built the HPLC profiles. QQX and WY performed the data analysis. PCS, YFX and ZXL reviewed the manuscript.
All authors read and approved the final manuscript. Correspondence to Yan-Fang Xian or Zhi-Xiu Lin. The authors declare that there is no conflict of interest in relation to the publication of this article. Springer Nature remains neutral with respect to jurisdictional claims in published maps and institutional affiliations.
Provided by Springer Nature's ShareEdit content sharing initiative. Most commercial cat's claw preparations consist of the plant species Uncaria tomentosa, although there are 34 other known species of cat's claw besides Uncaria tomentosa33,34. When choosing a cat's claw nootropic supplement, you should know that at least 12 different and unrelated herbs such as Cat's Claw or Cat's Claw have been marketed. Cat's claw PTI-00703 represents a dry extract of cat's claw (Uncaria tomentosa) extracted by a specific manufacturing company in Peru. Cat's claw (Uncaria tomentosa, Cat's Claw or Savéntaro) is a large, woody vine from South America that gets its name from the hook-shaped spines on the leaf stem, which resemble the claws of a cat.
