Chem Support 5™

Chem Support 5™ — (tonic) with Graviola and supporting herbs — This proprietary blend of herbs provides support when allopathic (chemotherapy) treatment is required. Research shows cytotoxic (anti-tumor) activity against several cancer cell lines.2,3,4,5,6,7,8,9,10,12,13,18,19,20,21,23,24,25,26,27,32 Chem Support 5™ enhances the immune system, DNA repair, and cell recovery after chemotherapy induced DNA damage.1,8,11,14,16,17,25,30,31 Used to reduce inflammation, protect cells, and suppress cancer cell growth.1,6,7,8,9,14,16,17, 21,28,29 Chem Support 5™ helps to counteract the damaging effects of treatment by aiding in elimination of toxins from the body.9,11,17,30,31

1. In vitro antioxidant studies in leaves of Annona species.br /> Baskar R, Rajeswari V, Kumar TS.
Department of Biotechnology, Kumaraguru College of Technology, Coimbatore 641 006, India. bhubaski@rediffmail.com. Indian J Exp Biol. 2007 May;45(5):480-5.
PMID: 17569293 [PubMed - indexed for MEDLINE]

18. [Intratumoral administration of biological preparations--recommendation for integrative medicine][Article in Japanese]
Ebina T.
Division of Immunology, Research Institute, Miyagi Cancer Center.
Gan To Kagaku Ryoho. 2001 Oct;28(11):1515-8.
PMID: 11707968 [PubMed - indexed for MEDLINE]

23. A lapachol derivative active against mouse lymphocytic leukemia P-388.
da Consolacao M, Linardi F, de Oliveira MM, Sampaio MR.
J Med Chem. 1975 Nov;18(11):1159-61.
PMID: 1177264 [PubMed - indexed for MEDLINE]

30. DNA repair enhancement of aqueous extracts of Uncaria tomentosa in a human volunteer study.
Sheng Y, Li L, Holmgren K, Pero RW.Department of Cell and Molecular Biology, Section of Tumor and Immune Biology, University of Lund, Sweden. Yezhou.Sheng@wblab.lu.se.
Phytomedicine. 2001 Jul;8(4):275-82.
PMID: 11515717 [PubMed - indexed for MEDLINE]

31. Enhanced DNA repair, immune function and reduced toxicity of C-MED-100, a novel aqueous extract from Uncaria tomentosa.
Sheng Y, Bryngelsson C, Pero RW.Department of Cell and Molecular Biology, University of Lund, Sweden. yezhou.sheng@wblab.lu.se
J Ethnopharmacol. 2000 Feb;69(2):115-26.
PMID: 10687868 [PubMed - indexed for MEDLINE]

32. Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa.
Sheng Y, Pero RW, Amiri A, Bryngelsson C.
Department of Cell and Molecular Biology, University of Lund,
PMID: 9858909 [PubMed - indexed for MEDLINE]

1. In vitro antioxidant studies in leaves of Annona species.
Baskar R, Rajeswari V, Kumar TS.
Department of Biotechnology, Kumaraguru College of Technology, Coimbatore 641 006, India. bhubaski@rediffmail.com. Indian J Exp Biol. 2007 May;45(5):480-5.
Antioxidant potential of leaves of three different species of Annona was studied by using different in vitro models eg., 1,1-diphenyl-2-picryl hydrazyl (DPPH), 2,2-azinobis-(3-ethylbenzothizoline-6-sulphonate) (ABTS), nitric oxide, superoxide, hydroxy radical and lipid peroxidation. The ethanolic extract of A. muricata at 500 microg/ml showed maximum scavenging activity (90.05%) of ABTS radical cation followed by the scavenging of hydroxyl radical (85.88%) and nitric oxide (72.60%) at the same concentration. However, the extract showed only moderate lipid peroxidation inhibition activity. In contrast, the extract of A. reticulata showed better activity in quenching DPPH (89.37%) and superoxide radical (80.88%) respectively. A.squamosa extract exhibited least inhibition in all in vitro antioxidant models excepting hydroxyl radical (79.79%). These findings suggest that the extracts of A. muricata possess potent in vitro antioxidant activity as compared to leaves of A. squamosa and A. reticulata suggesting its role as an effective free radical scavenger, augmenting its therapeutic
PMID: 17569293 [PubMed - indexed for MEDLINE]

2. Antiprotozoal and cytotoxic activities in vitro of Colombian Annonaceae.
Osorio E, Arango GJ, Jiménez N, Alzate F, Ruiz G, Gutiérrez D, Paco MA, Giménez A, Robledo S.
Grupo de Investigación en Sustancias Bioactivas (GISB), Facultad de Química Farmacéutica, Corporación de Patologías Tropicales, Universidad de Antioquia, A.A. 1226, Medellín, Colombia. josorio@farmacia.udea.edu.co.
J Ethnopharmacol. 2007 May 22;111(3):630-5. Epub 2007 Jan 18.
Ethnobotanical and chemotaxonomical studies for antiparasitic activity of Colombian Annonaceae were carried out. In vitro antiprotozoal activity of 36 extracts obtained from six different species was determined against promastigotes of three Leishmania species, epimastigotes of Trypanosoma cruzi and both chloroquine sensitive (F32) and resistant (W2) Plasmodium falciparum. Cytotoxic activity was evaluated in U-937 cells. Active extracts were selected according their selectivity index (SI). Extracts from Annona muricata, Rollinia exsucca, Rollinia pittieri and Xylopia aromatica were active against Leishmania spp. and Trypanosoma cruzi showing IC50 values lower than 25 microg/ml. Hexane extract from Rollinia pittieri leaves was the most selective against Trypanosoma cruzi and Leishmania spp. (IS=10 and 16, respectively). The extracts from Desmopsis panamensis, Pseudomalmea boyacana, Rollinia exsucca and Rollinia pittieri showed good antiplasmodial activity (IC50 < 10 microg/ml). No correlation between antiplasmodial activity and inhibition of beta-hematin production was found. The present study gives specific and useful information about antiprotozoal and cytotoxic activities of some Annonaceae extracts. Results presented here also demonstrate which plants and/or plant parts could be useful in the treatment of leishmaniasis, Chagas’ disease and malaria.
PMID: 17296281 [PubMed - indexed for MEDLINE]

3. New cytotoxic monotetrahydrofuran annonaceous acetogenins from Annona muricata.
Liaw CC, Chang FR, Lin CY, Chou CJ, Chiu HF, Wu MJ, Wu YC.Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Republic of China.
J Nat Prod. 2002 Apr;65(4):470-5.
Three new monotetrahydrofuran annonaceous acetogenins, muricin H (1), muricin I (2), and cis-annomontacin (3), along with five known acetogenins, annonacin, annonacinone, annomontacin, murisolin, and xylomaticin, were isolated from the seeds of Annona muricata. Additionally, two new monotetrahydrofuran annonaceous acetogenins, cis-corossolone (4) and annocatalin (5), together with four known ones, annonacin, annonacinone, solamin, and corossolone, were isolated from the leaves of this species. The structures of all new isolates were elucidated and characterized by spectral and chemical methods. These new acetogenins exhibited significant activity in in vitro cytotoxic assays against two human hepatoma cell lines, Hep G(2) and 2,2,15. Compound 5 showed a high selectivity toward the Hep 2,2,15 cell line.
PMID: 11975482 [PubMed - indexed for MEDLINE]

4. Novel cytotoxic annonaceous acetogenins from Annona muricata.
Chang FR, Wu YC.
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan, Republic of China.
J Nat Prod. 2001 Jul;64(7):925-31.
Seven new annonaceous acetogenins, muricins A-G (1-7), as well as five known compounds, a mixture of muricatetrocin A (8) and muricatetrocin B (9), longifolicin (10), corossolin (11), and corossolone (12), were isolated from the seeds of Annona muricata. The structures of all isolates were elucidated and characterized by spectral and chemical methods. These acetogenins showed significantly selective in vitro cytotoxicities toward the human hepatoma cell lines Hep G(2) and 2,2,15.
PMID: 11473425 [PubMed - indexed for MEDLINE]

5. Antitumor and Antiviral Activity of Colombian Medicinal Plant Extracts
LA Betancur-Galvis/+, J Saez*, H Granados*, A Salazar**, JE Ossa
Laboratorio de Virología, Departamento de Microbiología y Parasitología, Facultad de Medicina *Departamento
de Química **Departamento de Biología, Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia,
Apartado 1226, Medellín, Colombia.
531 Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 94(4): 531-535, Jul./Aug. 1999
Extracts of nine species of plants traditionally used in Colombia for the treatment of a variety of diseases were tested in vitro for their potential antitumor (cytotoxicity) and antiherpetic activity. MTT (Tetrazolium blue) and Neutral Red colorimetric assays were used to evaluate the reduction of viability of cell cultures in presence and absence of the extracts. MTT was also used to evaluate the effects of the extracts on the lytic activity of herpes simplex virus type 2 (HSV-2). The 50% cytotoxic concentration (CC50) and the 50% inhibitory concentration of the viral effect (EC50) for each extract were calculated by linear regression analysis. Extracts from Annona muricata, A. cherimolia and Rollinia membranacea, known for their cytotoxicity were used as positive controls. Likewise, acyclovir and heparin were used as positive controls of antiherpetic activity. Methanolic extract from Annona sp. on HEp-2 cells presented a CC50 value at 72 hr of 49.6x103 g/ml. Neither of the other extracts examined showed a significant cytotoxicity. The aqueous extract from Beta vulgaris, the ethanol extract from Callisia grasilis and the methanol extract Annona sp. showed some antiherpetic activity with acceptable therapeutic indexes (the ratio of CC50 to EC50). These species are good candidates for further activity-monitored fractionation to identify active principles.
PMID: 10446015 [PubMed - indexed for MEDLINE]

6. Flavonoid-rich fraction of Maytenus ilicifolia Mart. ex. Reiss protects the gastric mucosa of rodents through inhibition of both H+,K+ -ATPase activity and formation of nitric oxide.
Baggio CH, Freitas CS, Otofuji Gde M, Cipriani TR, Souza LM, Sassaki GL, Iacomini M, Marques MC, Mesia-Vela S.
Department of Pharmacology, Sector of Biological Sciences, Universidade Federal do Paraná, Curitiba, PR, Brazil.
J Ethnopharmacol. 2007 Sep 25;113(3):433-40. Epub 2007 Jul 3.
Maytenus ilicifolia Mart. ex. Reissek (Celastraceae), a medicinal plant known in Brazil as “espinheira-santa” is commonly used to treat gastric disorders. The effect of the flavonoid-rich fraction separated from the leaves was evaluated for its gastroprotective properties and the mechanism(s) involved in this activity. Intraperitoneal administration of the flavonoid-rich fraction potently protected rats from experimentally induced chronic (ED(50)=79 mg/kg) and acute gastric lesions by ethanol (ED(50)=25mg/kg) and indomethacin (ED(50)=4 mg/kg) without altering the decreased amount of cytoprotective glutathione and mucus amount in the injured gastric mucosa. A potent reduction of gastric acid hypersecretion (ED(50)=7 mg/kg, i.p.) was accompanied by a reduction of nitric oxide release (ED(50)=1.6 mg/kg, i.p.) in the gastric secretion of 2h pylorus ligated rats which suggests an important role for nitric oxide-dependent mechanisms. Inhibition of gastric acid secretion in vivo was correlated with the in vitro inhibition of rabbit gastric H(+),K(+)-ATPase activity (IC(50)=41 microg/mL). Chemical investigation of the fraction showed galactitol (25%), epicatechin (3.1%) and catechin (2%) as the majoritary components. Collectively, the results show that the flavonoid-rich fraction of Maytenus ilicifolia potently protects animals from gastric lesions with high potency through inhibition of gastric acid secretion.
PMID: 17706386 [PubMed - in process]

7. Folate receptor-specific antitumor activity of EC131, a folate-maytansinoid conjugate.
Reddy JA, Westrick E, Santhapuram HK, Howard SJ, Miller ML, Vetzel M, Vlahov I, Chari RV, Goldmacher VS, Leamon CP.
Endocyte, Inc., West Lafayette, Indiana 47906, USA.
Cancer Res. 2007 Jul 1;67(13):6376-82.
EC131, a new folate receptor (FR)-targeted drug conjugate, was prepared by covalently attaching the vitamin folic acid (FA) to a potent microtubule-inhibiting agent, maytansinoid DM1, via an intramolecular disulfide bond. When tested on cells in culture, EC131 was found to retain high affinity for FR-positive cells and to provide FR-specific cytotoxicity with an IC(50) in the low nanomolar range. The activity of EC131 was completely blocked in the presence of an excess of free FA, and no activity was detected against FR-negative cells. When evaluated against s.c. FR-positive M109 tumors in BALB/c mice, EC131 showed marked antitumor efficacy. Furthermore, this therapeutic effect occurred in the apparent absence of weight loss or noticeable organ tissue degeneration. In contrast, no significant antitumor activity was observed in EC131-treated animals that were codosed with an excess of FA, thus demonstrating the targeted specificity of the in vivo activity. EC131 also showed marked antitumor activity against FR-positive human KB tumors, but not against FR-negative A549 tumors, in nude mice with no evidence of systemic toxicity during or after the therapy. In contrast, therapy with the free maytansinoid drug (in the form of DM1-S-Me) proved not to be effective against the KB model when administered at its maximum tolerated dose (MTD). Taken together, these results indicate that EC131 is a highly potent agent capable of producing therapeutic benefit in murine tumor models at sub-MTD levels.
PMID: 17616697 [PubMed - indexed for MEDLINE]

8. Antioxidant activity of Maytenus ilicifolia root bark.
Vellosa JC, Khalil NM, Formenton VA, Ximenes VF, Fonseca LM, Furlan M, Brunetti IL, Oliveira OM.
Biochemistry and Technology Chemistry Department, Instituto de Química, UNESP, Araraquara-SP, Brazil. josevellosa@yahoo.com.br
Fitoterapia. 2006 Apr;77(3):243-4. Epub 2006 Mar 6.
Maytenus ilicifolia is an important plant with potential on cancer treatment and has been largely used in Brazil and other countries. We have evaluated the crude ethanolic extract of M. ilicifolia as a potential antioxidant source using an assay based on the bleaching of the radical monocation 2,2’-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(*+)) and by HOCl scavenger capacity. Trolox and uric acid were used as positive controls. The results indicated M. ilicifolia root bark as a great source of antioxidants based on its potential as scavenger of radicals.
PMID: 16567059 [PubMed - indexed for MEDLINE]

9. Evaluation of antinociceptive, anti-inflammatory and antiulcerogenic activities of Maytenus ilicifolia.
Jorge RM, Leite JP, Oliveira AB, Tagliati CA.
Laboratório de Toxicologia Experimental, Faculdade de Farmácia, UFMG, Av. Olegário Maciel, 2360/613, 30180-112, Belo Horizonte, MG, Brazil.
J Ethnopharmacol. 2004 Sep;94(1):93-100.
Maytenus ilicifolia (Celastraceae) is a native plant from Tropical Atlantic Forest (Mata Atlântica, Brazil) called ‘espinheira-santa’. This plant is traditionally used as anti-inflammatory, analgesic and antiulcerogenic. Many studies focusing pharmacological and toxicological aspects of the plant have been performed. The aim of this study is to evaluate the efficacy (anti-inflammatory and antinociceptive activities and protection against gastric lesions, including cytoprotection and healing) and phytochemical profile of hexane and ethylacetate extracts of Maytenus ilicifolia. Per os administration of these extracts inhibited nociception and formaldehyde-induced paw oedema in mice and carrageenin-induced paw oedema in rats. Severity of gastric lesions induced by cold-restraint stress (-18 degrees C for 45 min) method was also clearly reduced in rats considering both cytoprotection and healing aspects. Administration of the extracts led to volume gastric and pH increase. These results suggest that hexane and ethylacetate extracts of Maytenus ilicifolia may represent an important clinical alternative in anti-inflammatory and antiulcerogenic therapeutics, though, further experiments should be performed to confirm this assertion.
PMID: 15261968 [PubMed - indexed for MEDLINE]

10. Quantitative determination for cytotoxic Friedo-nor-oleanane derivatives from five morphological types of Maytenus ilicifolia (Celastraceae) by reverse-phase high-performance liquid chromatography.
Buffa Filho W, Corsino J, Bolzani da SV, Furlan M, Pereira AM, França SC.
Núcleo de Bioensaio, Biossíntese e Ecofisiologia de Produtos Naturais, Instituto de Química, Universidade Estadual Paulista, CP. 355, 14801-970, Araraquara-SP, Brazil.
Phytochem Anal. 2002 Mar-Apr;13(2):75-8.
Five different morphological types of Maytenus ilicifolia of the same age and harvested under the same conditions showed distinct accumulations of some friedo-nor-oleananes. A rapid, sensitive and reliable reverse-phase HPLC method (employing an external standard) was used for the determination of the cytotoxic triterpenoids, 20 alpha-hydroxymaytenin, 22 beta-hydroxymaytenin, maytenin, celastrol and pristimerin in each of the five types. Well resolved peaks with good detection response and linearity in the range 1.0-100 micrograms/mL were obtained.
PMID: 12018026 [PubMed - indexed for MEDLINE]

11. Assessment of the effect of Maytenus ilicifolia (espinheira santa) extract on the labeling of red blood cells and plasma proteins with technetium-99m.
de Oliveira JF, Braga AC, de Oliveira MB, Avila AS, Caldeira-de-Araújo A, Cardoso VN, Bezerra RJ, Bernardo-Filho M.
Universidade do Estado do Rio de Janeiro, Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biofísica e Biometria. Av. 28 de Setembro, 87, Rio de Janeiro, RJ 20551-030, Brazil.
J Ethnopharmacol. 2000 Sep;72(1-2):179-84.
We are trying to develop a model to assess properties of products utilized in popular medicine. Maytenus ilicifolia is used in herbal medicine. Red blood cells (RBC) labeled with technetium-99m (99mTc) are employed in nuclear medicine. This labeling procedure depends on a reducing agent and stannous chloride is used. There is evidence that this labeling may be altered by drugs. We have investigated the possibility of M. ilicifolia extract being capable to alter the labeling of blood elements with 99mTc. Blood was incubated with M. ilicifolia extract. Stannous chloride solution and Tc-99m were added. Blood was centrifuged and plasma (P) and blood cells (C) were isolated. Samples of P or C were also precipitated, centrifuged and insoluble (IF) and soluble (SF) were separated. The percentages of radioactivity (%ATI) in C, IF-P and IF-C was calculated. The %ATI decreased on C from 93.6+/-2.3 to 29.0+/-2.7, on IF-P from 77.6+/-1.2 to 7.5+/-1.0 and on IF-C from 80.0+/-3.4 to 12.6+/-4.8. Once in RBC labeling procedure with 99mTc depends on the presence of stannous (+2) ions, the substances of the M. ilicifolia extract could increase the valence these ions to stannic (+4). This fact would decrease the %ATI on blood elements and indicate the presence of oxidant agents in the M. ilicifolia extract.
PMID: 10967470 [PubMed - indexed for MEDLINE]

12. New phenolic and quinone-methide triterpenes from Maytenus amazonica.
Chávez H, Estévez-Braun A, Ravelo AG, González AG.
Instituto Universitario de Bio-Orgánica “Antonio González”, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez 2, 38206, Tenerife, Canary Islands, Spain.
J Nat Prod. 1999 Mar;62(3):434-6.
The new nortriterpene methylene quinones amazoquinone (1) and (7S, 8S)-7-hydroxy-7,8-dihydro-tingenone (2), and the new norphenolic triterpenes 7,8-dihydro-6-oxo-tingenol (3), 23-nor-6-oxo-tingenol (4), and 23-oxo-iso-tingenone (5) were isolated from Maytenus amazonica. Their structures were elucidated by spectroscopic methods. Compounds 1, 2, 3, and 5 showed low antitumor activity against four cancer cell lines.
PMID: 10096852 [PubMed - indexed for MEDLINE]

13. Cytotoxic aromatic triterpenes from Maytenus ilicifolia and Maytenus chuchuhuasca.
Shirota O, Morita H, Takeya K, Itokawa H.
Department of Pharmacognosy, Tokyo College of Pharmacy, Japan.
J Nat Prod. 1994 Dec;57(12):1675-81.
The isolation and structure elucidation of four cytotoxic aromatic triterpenes [1-4] along with three known quinoid triterpenes [5-7] from the South American medicinal plants Maytenus ilicifolia and M. chuchuhuasca are described. The structures of these aromatic triterpenes contained aromatized A rings and C-6 oxygenated B rings, and were elucidated by 1H- and 13C-nmr spectroscopic studies and by X-ray crystallographic analysis of 3.
PMID: 7714534 [PubMed - indexed for MEDLINE]

Mutamba ‘Guazuma ulmifolia’

14. The aerial parts of Guazuma ulmifolia Lam. protect against NSAID-induced gastric lesions.
Berenguer B, Trabadela C, Sánchez-Fidalgo S, Quílez A, Miño P, De la Puerta R, Martín-Calero MJ.
Department of Pharmacology, Faculty of Pharmacy, University of Seville, Professor García González Street 2, 41012 Sevilla, Spain.
J Ethnopharmacol. 2007 Nov 1;114(2):153-60. Epub 2007 Jul 22.
Guazuma ulmifolia Lam., a member of the Sterculiaceae family, is used in folk medicine because of its antioxidant, antimicrobial and antihypertensive properties. Most of the research work carried out on this plant has focused on the bark because of its high concentration of antioxidant proanthocyanidins. The flowers and leaves of Guazuma ulmifolia, though less studied, are also used as a remedy for different conditions, such as kidney and gastrointestinal diseases, fever and diabetes. The aim of this study was to assess the gastroprotective effects of an aqueous suspension of the ethanolic extract from leaves and flowers of Guazuma ulmifolia in a model of acute gastric ulcer induced by diclofenac as ulcerogenic agent, using the proton pump inhibitor omeprazole as a protection reference. Therefore, the extract was administered two times orally to three groups of Wistar rats at doses of 500, 250 and 125mg/kg, with a 24-h interval between doses. Diclofenac (100mg/kg) was given 1h after the last administration of the extract. Pretreatment with Guazuma ulmifolia or omeprazole decreased the ulcerated area in a dose-dependent way. Myeloperoxidase activity as a marker of neutrophil infiltration was slightly reduced in vivo, whereas in vitro, anti-inflammatory activity was clearly inhibited in a dose-dependent way. The lowest doses of the extract significantly decreased the levels of lipoperoxides, and superoxide dismuthase activity increased to a similar extent as with omeprazole (P<0.001). Examination of glutathione metabolism reflected a significant rise in glutathione peroxidase activity at the highest dose of Guazuma ulmifolia. Finally, there was a faint elevation in prostaglandin E(2) levels with all doses, though the depletion induced by diclofenac could not be reverted. We conclude that the aerial parts of Guazuma ulmifolia protect gastric mucosa against the injurious effect of NSAIDs mainly by anti-inflammatory and radical-scavenging mechanisms.
PMID: 17884315 [PubMed - in process]

15. Antibacterial, antiprotozoal and antioxidant activity of five plants used in Izabal for infectious diseases.
Navarro MC, Montilla MP, Cabo MM, Galisteo M, Cáceres A, Morales C, Berger I.
Department of Pharmacology, Faculty of Pharmacy, University of Granada, Spain. cnavarro@platon.ugr.es
Phytother Res. 2003 Apr;17(4):325-9.
Methanol and aqueous extracts from five plant species, used in traditional medicine in Guatemala for the treatment of microbial infections, were tested in vitro for their ability to scavenge DPPH, OH(.) and O(2) (-) radicals and to inhibit lipoperoxidation (LPO) in order to establish a relationship between their antioxidant activities and their effects against infectious agents. Acalypha guatemalensis, Ocimum micranthum and Smilax spinosa possessed a significant activity against both the three free radicals assayed and LPO; Guazuma ulmifolia showed effects against DPPH and OH(.). Piper auritum showed no activity. These extracts were also evaluated for antibacterial and antiprotozoal activities. A. guatemalensis showed activity against Pseudomonas aeruginosa; S. spinosa was active against Salmonella typhi, and A. guatemalensis, and S. spinosa against Trypanosoma cruzi or Leishmania spp. Copyright 2003 John Wiley & Sons, Ltd.
PMID: 12722133 [PubMed - indexed for MEDLINE]

16. Search for new molecules, new treatments of old diseases or a better understanding of indigenous cultures?
Heinrich M.
Centre for Pharmacognosy and Phytotherapy, The School of Pharmacy, Univ. London, 29-39 Brunswick Square, London, WC1N 1AX, UK. phyto@ams1.ulsop.ac.uk
Curr Top Med Chem. 2003;3(2):141-54.
Results of various projects on Mexican Indian ethnobotany and some of the subsequent pharmacological and phytochemical studies are summarised focusing both on chemical-pharmacological as well as anthropological (ethnopharmacological) aspects of our research. We have identified taste and smell properties of medicinal (vs. non-medicinal) plants as important indigenous selection criteria. There exist well-defined criteria specific for each culture, which lead to the selection of a plant as a medicine. This field research has also formed a basis for studies on bioactive natural products from selected species. The bark of Guazuma ulmifolia showed antisecretory activity (cholera toxin-induced chloride secretion in rabbit distal colon in an USSING chamber). Active constituents are procyanidins with a polymerisation degree of eight or higher. Byrsonima crassifolia yielded proanthocyanidins with (+) epicatechin units and Baccharis conferta showed a dose-dependent antispasmodic effect with the effect being particularly strong in flavonoid-rich fractions. Our ethnopharmacological research led to the identification of sesquiterpene lactones (SLs) like parthenolide as potent and relatively specific inhibitors of the transcription factor NF-kappaB, an important mediator of the inflammatory process. The inhibitory effect of SLs is very strongly enhanced by the presence of such groups as the isoprenoid ring system, a lactone ring containing a conjugated exomethylene group (alpha-methylene-gamma-lactone) and an alpha,beta-unsaturated cyclopentenone or a conjugated ester moieties. Our work also elucidated the NF-kappaB inhibiting activity of the photosensitiser phaeophorbide A from Solanum diflorum (Solanaceae) in PMA induced HeLa cells. Hyptis verticillata yielded a series of lignans as well as sideritoflavone, rosmarinic acid and (R)-5-hydroxypyrrolidin-2-one and is rich in essential oil (rich in alpha-pinene, beta-pinene and thymol). Other species investigated include Begonia heracleifolia, Crossopetalum gaumerii, Epaltes mexicana, Pluchea symphytifolia and Xanthosoma robustum.
PMID: 12570770 [PubMed - indexed for MEDLINE]

17. Inhibition of intestinal chloride secretion by proanthocyanidins from Guazuma ulmifolia.
Hör M, Rimpler H, Heinrich M.
Institut für Pharmazeutische Biologie, Albert-Ludwigs-Universität, Freiburg, Germany.
Planta Med. 1995 Jun;61(3):208-12.
The antisecretory activity of Guazuma ulmifolia bark was examined in rabbit distal colon mounted in an Ussing chamber. Chloride secretion was stimulated by cholera toxin and prostaglandin E2 (PGE2). Guazuma ulmifolia extract (GUE) completely inhibited cholera toxin-induced secretion if the extract was added to the mucosal bath prior to the toxin. Adding the extract after administration of the toxin had no effect on secretion. GUE did not inhibit PGE2-induced chloride secretion. These results indicate an indirect antisecretory mechanism. SDS-PAGE analysis of cholera toxin treated with GUE confirmed this presumption. GUE specifically interacted with the A subunit of the toxin. Preliminary phytochemical examinations showed that the most active fraction contains procyanidins with a degree of polymerisation higher than 8.
PMID: 7617760 [PubMed - indexed for MEDLINE]

Pau d’Arco ‘Tabebuia impetignosa’

18. [Intratumoral administration of biological preparations--recommendation for integrative medicine][Article in Japanese]
Ebina T.
Division of Immunology, Research Institute, Miyagi Cancer Center.
Gan To Kagaku Ryoho. 2001 Oct;28(11):1515-8.
The antitumor effect of biological preparations was examined in a double grafted tumor system. PSK is a hot water extract of cultured mycelia from Coliolus versicolor. Its protein content is about 38% and the main glycoside portion of PSK is beta-D-glucan. Lentinan is purified from fruit bodies of Lentinus edodes and is a beta-1, 3-glucan. Cepharanthin is an extract from the root of Stephania cepharantha HAYATA, consisting of 4 kinds of biscoclaurine alkaloids. TAHEEBO tea is a hot water extract of Tabebuia avellanedae, the active ingredient of which is naphthoquinones. If protein-bound polysaccharides were to be used in Western medicine, these polysaccharides would be purified, but purified beta-glucan loses its beneficial effects. Similarly, when raw Cepharanthin is purified to isolate its active ingredient (an alkaloid cepharanthine), its anti-tumor effect is weakened. Clear IAP induction was observed in serum of mice treated with extracts of Coliolus versicolor and Stephania cepharantha. However, IAP induction was not observed in the serum of mice treated with purified beta-glucan or purified alkaloid. This suggests that macrophages may recognize extracts but not purified substances. In Western medicine, purified substances with known chemical structures are recognized as drugs, but overdoses of these drugs are toxic to the body, thus adverse reactions are always an issue. In Chinese medicine, mixtures containing several crude drugs are recognized as drugs, whose active ingredients are not identified. In integrative medicine, drugs are extracts that contain active ingredients with known structures and functions. We propose a Japanese version of integrative medicine which is neither Western nor Chinese.
PMID: 11707968 [PubMed - indexed for MEDLINE]

19. Beta-lapachone, a quinone isolated from Tabebuia avellanedae, induces apoptosis in HepG2 hepatoma cell line through induction of Bax and activation of caspase.
Woo HJ, Park KY, Rhu CH, Lee WH, Choi BT, Kim GY,Park YM, Choi YH.
Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan, Korea. J Med Food. 2006
Summer;9(2):161-8.
The DNA topoisomerase inhibitor beta-lapachone is a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae) in South America. It has been reported to possess a wide range of pharmacological properties, and is a promising cancer chemopreventive agent. In this study, the effects of beta-lapachone on the growth of the human hepatoma cell line HepG2 were investigated. The results showed that beta-lapachone inhibits the viability of HepG2 by inducing apoptosis, as evidenced by the formation of apoptotic bodies and DNA fragmentation. Reverse transcription-polymerase chain reaction and immunoblotting results indicated that treatments of cells with beta-lapachone resulted in down-regulation of anti-apoptotic Bcl-2 and Bcl-X(L) and up-regulation of pro-apoptotic Bax expression. beta-Lapachone-induced apoptosis was associated with a proteolytic activation of caspase-3 and -9 and degradation of poly(ADP-ribose) polymerase protein. However, beta-lapachone treatment did not affect the inhibitor of apoptosis proteins family and the Fas/FasL system. Taken together, our study indicated that beta-lapachone may have potential as a chemopreventive agent for liver cancer.
PMID: 16822200 [PubMed - indexed for MEDLINE]

20. Beta-lapachone induces growth inhibition and apoptosis in bladder cancer cells by modulation of Bcl-2 family and activation of caspases.
Lee JI, Choi DY, Chung HS, Seo HG, Woo HJ, Choi BT, Choi YH.
R&E Program, Korea Science Academy, Busan, South Korea. Exp Oncol. 2006 Mar;28(1):30-5.
AIM: To study in vitro the molecular mechanism of apoptosis caused by beta-lapachone, a quinone obtained from the bark of the lapacho tree (Tabebuia avellanedae). MATERIALS AND METHODS: The study was carried out on human bladder carcinoma T24 cell line. Determination of cell viability was done using trypan blue exclusion method, apoptosis quantitative estimation - by DAPI staining and agarose gel electrophoresis for DNA fragmentation. Flow cytometry analysis, RT-PCR and Western blot analysis, colorimetric assay of caspase activity were applied as well. RESULTS: It was found that in micromolar range of concentrations beta-lapachone inhibited the viability of T24 cells by inducing apoptosis, which could be proved by formation of apoptotic bodies and DNA fragmentation. Treatment of T24 cells with beta-lapachone resulted in a down-regulation of Bcl-2 expression and up-regulation of Bax expression. beta-lapachone-induced apoptosis was also associated with activation of caspase-3 and caspase-9, inhibition of IAP expression, and degradation of poly (ADP-ribose) polymerase, phospholipase C-gamma1 and beta-catenin proteins. At the same time Fas and FasL levels were inhibited upon treatment with beta-lapachone in a concentration-dependent manner. Conclusion: beta-lapachone-induced apoptosis in T24 cells is mediated, at least in part, by the mitochondrial-signaling pathway.
PMID: 16614704 [PubMed - indexed for MEDLINE]

21. Demonstration of the lapachol as a potential drug for reducing cancer metastasis.
Balassiano IT, De Paulo SA, Henriques Silva N, Cabral MC, da Gloria da Costa Carvalho M.
Instituto de Biofisica Carlos Chagas Filho, Laboratorio de Controle da Expressao Genica, Universidade Federal do Rio de Janeiro, Centro de Ciencias da Saude, Bloco C, Cidade Universitaria, CEP 21949-900, Rio de Janeiro, RJ, Brasil.
Oncol Rep. 2005 Feb;13(2):329-33.
Metastasis is the major process responsible for the death in cancer patients. In the search for more effective antineoplasic drugs, many substances are under investigation, among them lapachol. This study aims to examine the molecular and morphological alterations caused by lapachol treatment, as well as its effects on the intrinsic tissue invasive property of this cell line. HeLa cells were exposed to different concentrations of lapachol, and the resulting alterations on cellular protein profile, morphology and invasiveness property were studied. At 400 microg/ml, cellular viability remains unchanged, but lapachol induces alterations in the protein profile and inhibits the invasiveness of HeLa cells in CAM model. With these results, we can conclude that lapachol has a great potential of application in fighting metastasis.
PMID: 15643520 [PubMed - indexed for MEDLINE]

22. Cyclopentene dialdehydes from Tabebuia impetiginosa.
Koyama J, Morita I, Tagahara K, Hirai K.Kobe Pharmaceutical University, Japan. j-koyama@kobepharma-u.ac.jp.
Phytochemistry. 2000 Apr;53(8):869-72.
The isolation of two cyclopentene dialdehydes, 2-formyl-5-(4’-methoxybenzoyloxy)-3-methyl-2-cyclopentene-1-acetal dehyde, and 2-formyl-5-(3’, 4’-dimethoxybenzoyloxy)-3-methyl-2-cyclopentene-1-acetaldehyde, from the bark of Tabebuia impetiginosa is reported. The structures were established by analysis of spectroscopic data. These compounds showed anti-inflammatory activity.
PMID: 10820794 [PubMed - indexed for MEDLINE]

23. A lapachol derivative active against mouse lymphocytic leukemia P-388.
da Consolacao M, Linardi F, de Oliveira MM, Sampaio MR.
J Med Chem. 1975 Nov;18(11):1159-61.
Lapachol [2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone] and its analogs [2-(3,7-dimethyl-2,6-octadienyl)-3-hydroxy-1,4-naphthoquinone and 2-(3,3-dibromo-2-propenyl)-3-hydroxy-1,4-naphthoquinone] have been described, among almost a hundred synthesized analogs, as active against rat tumor Walker 256 carcinosarcoma. The acetylglucosylation of lapachol results in a compound which extends lapachol activity becoming effective against mouse lymphocytic leukemia P-388. When mice inoculated with 10(6) leukemic cells were treated with the drug during 9 days, their life span increased 80% over the control animals. Identification spectral data (uv, ir, 1H NMR, and MS) of the compound obtained by synthesis are given.
PMID: 1177264 [PubMed - indexed for MEDLINE]

24. Suppression of Human Prostate Cancer Cell Growth by β-Lapachone via Down-regulation of pRB Phosphorylation and Induction of Cdk Inhibitor p21WAF1/CIP1
Yung Hyun Choi*, Ho Sung Kang† and Mi-Ae Yoo†
Department of Biochemistry, College of Oriental Medicine, Dong-Eui University and Research Center for Oriental
Medicine, Pusan 614-052, Korea Department of Molecular Biology, College of Natural Sciences, Pusan National
University, Pusan 609-735, Korea
Received 31 October 2002, Accepted 22 November 2002
The product of a tree (Tabebuia avellanedae) from South America, β-lapachone, is known to exhibit various pharmacological properties, the mechanisms of which are poorly understood. The aim of the present study was to further elucidate the possible mechanisms by which β-lapachone exerts its anti-proliferative action in culturedhuman prostate cancer cells. We observed that the proliferation-inhibitory effect of β-lapachone was due to the induction of apoptosis, which was confirmed by observing the morphological changes and cleavage of the poly(ADP-ribose) polymerase protein. A DNA flow cytometric analysis also revealed that β-lapachone arrested the cell cycle progression at the G1 phase. The effects were associated with the down-regulation of the phosphorylation of the retinoblastoma protein (pRB) as well as the enhanced binding of pRB and the transcription factor E2F-1. Also, β-lapachone suppressed the cyclindependent kinases (Cdks) and cyclin E-associated kinase activity without changing their expressions. Furthermore, this compound induced the levels of the Cdk inhibitor p21WAF1/CIP1 expression in a p53-independent manner, and the p21 proteins that were induced by β-lapachone were associated with Cdk2. β-lapachone also activated the reporter construct of a p21 promoter. Overall, our results demonstrate a combined mechanism that involves the inhibition of pRB phosphorylation and induction of p21 as targets for β-lapachone. This may explain some of its anticancer effects.
KSBMB & Springer-Verlag 2003

Cat’s Claw ‘Unicaria tomentosa’

25. Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa.
Sheng Y, Pero RW, Wagner H.Department of Cell and Molecular Biology, University of Lund, Sweden. Yezhou.Sheng@wblab.lu.se
The Uncaria tomentosa water extracts (C-Med-100) depleted of indole alkaloids (< 0.05%, w/w) have been shown to induce apoptosis and inhibit proliferation in tumor cells in vitro and to enhance DNA repair, mitogenic response and white blood cells in vivo. In this study, the effect of C-Med-100 in the treatment of chemically induced leukopenia was evaluated in a rat model. W/Fu rats were treated first with doxorubicin (DXR) 2 mg/kg x 3 (i.p. injection at 24 hour-intervals) to induce leukopenia. Twenty-four hours after the last DXR treatment, the rats were daily gavaged with C-Med-100 for 16 consecutive days. As a positive control, Neupogen, a granulocyte colony stimulator was also administered by subcutaneous injection at a dose of 5 and 10 microg/ml for 10 consecutive days. The results showed that both C-Med-100 and Neupogen treatment groups recovered significantly sooner (p < 0.05 by Duncan test) than DXR group. However, the recovery by C-Med-100 treatment was a more natural process than Neupogen because all fractions of white blood cells were proportionally increased while Neupogen mainly elevated the neutrophil cells. These results were also confirmed by microscopic examination of the blood smears. The mechanism of the C-Med-100 effect on WBC is not known but other data showing enhanced effects on DNA repair and immune cell proliferative response support a general immune enhancement.
PMID: 10839217 [PubMed - indexed for MEDLINE]

26. An extract of Uncaria tomentosa inhibiting cell division and NF-kappa B activity without inducing cell death.
Akesson C, Lindgren H, Pero RW, Leanderson T, Ivars F.Section for Immunology, Department of Cell and Molecular Biology, BMC I:13, Lund University, Lund, SE-221 84, Sweden.
Int Immunopharmacol. 2003 Dec;3(13-14):1889-900.
Previous reports have demonstrated that extracts of the plant Uncaria tomentosa inhibit tumor cell proliferation and inflammatory responses. We have confirmed that C-Med 100, a hot water extract of this plant, inhibits tumor cell proliferation albeit with variable efficiency. We extend these findings by showing that this extract also inhibits proliferation of normal mouse T and B lymphocytes and that the inhibition is not caused by toxicity or by induction of apoptosis. Further, the extract did not interfere with IL-2 production nor IL-2 receptor signaling. Since there was no discrete cell cycle block in C-Med 100-treated cells, we propose that retarded cell cycle progression caused the inhibition of proliferation. Collectively, these data suggested interference with a common pathway controlling cell growth and cell cycle progression. Indeed, we provide direct evidence that C-Med 100 inhibits nuclear factor kappa B (NF-kappa B) activity and propose that this at least partially causes the inhibition of proliferation.
PMID: 14636838 [PubMed - in process]

27. The antiproliferative effects of Uncaria tomentosa extracts and fractions on the growth of breast cancer cell line.
Riva L, Coradini D, Di Fronzo G, De Feo V, De Tommasi N, De Simone F, Pizza C.Oncologia Sperimentale C, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Anticancer Res. 2001 Jul-Aug;21(4A):2457-61.
Uncaria tomentosa, also known as “Una de gato”, is a Rubiaceae species widely used in South-American folk medicine for the treatment of cancer, arthritis, gastritis and epidemic diseases. Extracts of the plant have been shown to possess cytostatic and anti-inflammatory activity as well as mutagenic and antimutagenic properties. However, to date no studies have been carried out to verify the direct antitumor activity of the extracts. The present study investigates the effects of some extracts and their chromatographic fractions from the bark of U. tomentosa on the growth of a human breast cancer cell line (MCF7). Our data indicated that, in addition to the antimutagenic activity, U. tomentosa extracts and fractions exert a direct antiproliferative activity on MCF7. The bioassay-directed fractionation from barks and leaves resulted in the isolation of two active fractions, which displayed an IC50 of 10 mg/ml and 20 mg/ml, respectively and an antiproliferative effect, with about 90% of inhibition at a concentration of 100 mg/ml.
PMID: 11724307 [PubMed - indexed for MEDLINE]

28. Cat’s claw inhibits TNFalpha production and scavenges free radicals: role in cytoprotection.
Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ.
Department of Pediatrics and Center for Cardiovascular Sciences, Albany Medical College, Albany, NY 12208, USA. sandovm@mail.amc.edu.
Free Radic Biol Med. 2000 Jul 1;29(1):71-8.
Cat’s claw (Uncaria tomentosa) is a medicinal plant from the Amazon River basin that is widely used for inflammatory disorders and was previously described as an inhibitor of NF-kappaB. Cat’s claw was prepared as a decoction (water extraction) of micropulverized bark with and without concentration by freeze-drying. Murine macrophages (RAW 264.7 cells) were used in cytotoxicity assays (trypan blue exclusion) in response to the free radical 1, 1-diphenyl-2-picrilhydrazyl (DPPH, 0.3 microM) and ultraviolet light (UV) light. TNFalpha production was induced by lipopolysaccharide (LPS 0.5 microg/ml). Cat’s claw was an effective scavenger of DPPH; the EC(50) value for freeze-dried concentrates was significantly less than micropulverized (18 vs. 150 microg/ml, p <.05). Cat’s claw (10 microg/ml freeze-dried) was fully protective against DPPH and UV irradiation-induced cytotoxicity. LPS increased TNFalpha media levels from 3 to 97 ng/ml. Cat’s claw suppressed TNFalpha production by approximately 65-85% (p <.01) but at concentrations considerably lower than its antioxidant activity: freeze-dried EC(50) = 1.2 ng/ml, micropulverized EC(50) = 28 ng/ml. In conclusion, cat’s claw is an effective antioxidant, but perhaps more importantly a remarkably potent inhibitor of TNFalpha production. The primary mechanism for cat’s claw anti-inflammatory actions appears to be immunomodulation via suppression of TNFalpha synthesis.
PMID: 10962207 [PubMed - indexed for MEDLINE]

29. C-Med 100, a hot water extract of Uncaria tomentosa, prolongs lymphocyte survival in vivo.
Akesson Ch, Pero RW, Ivars F.Sections for Immunology, Department of Cell and Molecular Biology, Lund University, Lund, Sweden.
Phytomedicine. 2003 Jan;10(1):23-33.
Water extracts of the bark of Uncaria tomentosa, a vine indigenous to South America, has been used for generations as an “immuno modulator”. To understand the basis of this immuno modulatory effect we fed mice in their drinking water with C-Med 100, which is a commercially available water extract from Uncaria tomentosa. We found a dose-dependent increase in spleen cell numbers in the supplemented mice, but the proportions of B cells, T cells, NK cells, granulocytes, and memory lymphocytes were normal. However, there were no detectable changes of the lymphoid architecture of the spleen even after long-term treatment. Further, when C-Med 100 treatment was interrupted the cellularity returned to normal level within four weeks. The increased number of lymphocytes was most likely not due to increased production because C-Med 100 did not have any significant effect on precursor cells nor on the accumulation of recent thymic emigrants in the spleen. We conclude that accumulation is
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