AMAZON HERB COMPANY

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Akhondzadeh S, Naghavi HR, Vazirian M, Shayeganpour A, Rashidi H, Khani M.


OBJECTIVE: Passionflower (Passiflora incarnata) is a folk remedy for anxiety. A double-blind randomized trial compared the efficacy of Passiflora incarnata extract with oxazepam in the treatment of generalized anxiety disorder. METHODS: The study was performed on 36 out-patients diagnosed with GAD using DSM IV criteria. Patients were allocated in a random fashion: 18 to the Passiflora extract 45 drops/day plus placebo tablet group, and 18 to oxazepam 30 mg/day plus placebo drops for a 4-week trial. RESULTS: Passiflora extract and oxazepam were effective in the treatment of generalized anxiety disorder. No significant difference was observed between the two protocols at the end of trial. Oxazepam showed a rapid onset of action. On the other hand, significantly more problems relating to impairment of job performance were encountered with subjects on oxazepam. CONCLUSION: The results suggest that Passiflora extract is an effective drug for the management of generalized anxiety disorder, and the low incidence of impairment of job performance with Passiflora extract compared to oxazepam is an advantage. A large-scale trial is justified.

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Ballard CG, O'Brien JT, Reichelt K, Perry EK.


BACKGROUND: Behavioral and psychological symptoms in dementia are frequent and are a major management problem, especially for patients with severe cognitive impairment. Preliminary reports have indicated positive effects of aromatherapy using select essential oils, but there are no adequately powered placebo-controlled trials. We conducted a placebo-controlled trial to determine the value of aromatherapy with essential oil of Melissa officinalis (lemon balm) for agitation in people with severe dementia. METHOD: Seventy-two people residing in National Health Service (U.K.) care facilities who had clinically significant agitation in the context of severe dementia were randomly assigned to aromatherapy with Melissa essential oil (N = 36) or placebo (sunflower oil) (N = 36). The active treatment or placebo oil was combined with a base lotion and applied to patients' faces and arms twice a day by caregiving staff. Changes in clinically significant agitation (Cohen-Mansfield Agitation Inventory [CMAI]) and quality of life indices (percentage of time spent socially withdrawn and percentage of time engaged in constructive activities, measured with Dementia Care Mapping) were compared between the 2 groups over a 4-week period of treatment. RESULTS: Seventy-one patients completed the trial. No significant side effects were observed. Sixty percent (21/35) of the active treatment group and 14% (5/36) of the placebo-treated group experienced a 30% reduction of CMAI score, with an overall improvement in agitation (mean reduction in CMAI score) of 35% in patients receiving Melissa balm essential oil and 11% in those treated with placebo (Mann-Whitney U test; Z = 4.1, p < .0001). Quality of life indices also improved significantly more in people receiving essential balm oil (Mann-Whitney U test; percentage of time spent socially withdrawn: Z = 2.6, p = .005; percentage of time engaged in constructive activities: Z = 3.5, p = .001). CONCLUSION: The finding that aromatherapy with essential balm oil is a safe and effective treatment for clinically significant agitation in people with severe dementia, with additional benefits for key quality of life parameters, indicates the need for further controlled trials.

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M.D. Ribeiro¹, G.M. Onusic¹, S.C. Poltronieri¹ and M.B. Viana<sup>2

1</sup>Laboratório de Psicofarmacologia, Departamento de Psicologia e Educação, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
²Departamento de Psicologia do Desenvolvimento, Faculdade de Psicologia, Pontifícia Universidade Católica, São Paulo, SP, Brasil

Abstract Erythrina velutina (EV) and Erythrina mulungu (EM), popularly used in Brazil as tranquilizing agents, were studied. The effects of acute and chronic oral treatment with a water:alcohol extract of EV (7:3, plant grounded stem bark; acute = 100, 200, 400 mg/kg; chronic = 50, 100, 200 mg/kg) were evaluated in rats (N = 11-12) submitted to the elevated T-maze (for avoidance and escape measurements) model of anxiety. This model was selected for its presumed capacity to elicit specific subtypes of anxiety disorders recognized in clinical practice: avoidance has been related to generalized anxiety and escape to panic. Additionally, animals were treated with the same doses of EV and EM (water:alcohol 7:3, inflorescence extract) and submitted to the forced swim test for the evaluation of antidepressant activity (N = 7-10). Both treatment regimens with EV impaired elevated T-maze avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (avoidance 1, mean ± SEM, acute study: 131.1 ± 45.5 (control), 9.0 ± 3.3 (diazepam), 12.7 ± 2.9 (200 mg/kg), 28.8 ± 15.3 (400 mg/kg); chronic study: 131.7 ± 46.9 (control), 35.8 ± 29.7 (diazepam), 24.4 ± 10.4 (50 mg/kg), 29.7 ± 11.5 (200 mg/kg)). Neither EV nor EM altered measurements performed in the forced swim test, in contrast to the reference drug imipramine that significantly decreased immobility time after chronic treatment. These results were not due to motor alterations since no significant effects were detected in an open field. These observations suggest that EV exerts anxiolytic-like effects on a specific subset of defensive behaviors which have been associated with generalized anxiety disorder.

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Wagner Vilegas, Miriam Sanommiya, Luca Rastrelli, and Cosimo Pizza

Instituto de Quimica de Araraquara, Universidade Estadual Paulista, C. Postal 355, 14801-970 Araraquara, SP, Brazil, and Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Piazza Vittorio Emanuele 9, 84084 Penta di Fisciano (SA), Italy

Droplet countercurrent chromatography and high-performance liquid chromatography fractionation of the aqueous infusion from Maytenus aquifolium Martius leaves afforded two flavonoid tetrasaccharides: quercetin 3-O-a-l-rhamnopyranosyl(1->6)-O-[ß-d-glucopyranosyl(1->3)-O-a-l-rhamnopyranosyl(1->2)-O-ß-d-galactopyranoside and kaempferol 3-O-a-l-rhamnopyranosyl(1->6)-O-[ß-d-glucopyranosyl(1->3)-O-a-l-rhamnopyranosyl(1->2)-O-ß-d-galactopyranoside. All structures were elucidated by spectroscopic methods. Pharmacological essays of the infusion showed antiulcer activity in rats.

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R. M. Jorge^a, J. P. V. Leite^b, A. B. Oliveira^b and C. A. Tagliati<sup>a

a</sup> Laboratório de Toxicologia Experimental, Faculdade de Farmácia, UFMG, Av. Olegário Maciel, 2360/613, 30180-112, Belo Horizonte, MG, Brazil
^b Departamento de Produtos Farmacêuticos da Faculdade de Farmácia da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

Abstract: Maytenus ilicifolia (Celastraceae) is a native plant from Tropical Atlantic Forest (Mata Atlântica, Brazil) called ‘espinheira-santa’. This plant is traditionaly 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 °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.

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Kennedy DO, Scholey AB, Tildesley NT, Perry EK, Wesnes KA.


Melissa officinalis (lemon balm) is a traditional herbal medicine, which enjoys contemporary usage as a mild sedative, spasmolytic and antibacterial agent. It has been suggested, in light of in vitro cholinergic binding properties, that Melissa extracts may effectively ameliorate the cognitive deficits associated with Alzheimer's disease. To date, no study has investigated the effects on cognition and mood of administration of Melissa to healthy humans. The present randomised, placebo-controlled, double-blind, balanced-crossover study investigated the acute effects on cognition and mood of a standardised extract of M. officinalis. Twenty healthy, young participants received single doses of 300, 600 and 900 mg of M. officinalis (Pharmaton) or a matching placebo at 7-day intervals. Cognitive performance was assessed using the Cognitive Drug Research (CDR) computerised test battery and two serial subtraction tasks immediately prior to dosing and at 1, 2.5, 4 and 6 h thereafter. In vitro IC(50) concentrations for the displacement of [3H]-(N)-nicotine and [3H]-(N)-scopolamine from nicotinic and muscarinic receptors in human occipital cortex tissue were also calculated. Results, utilising the cognitive factors previously derived from the CDR battery, included a sustained improvement in Accuracy of Attention following 600 mg of Melissa and time- and dose-specific reductions in both Secondary Memory and Working Memory factors. Self-rated "calmness," as assessed by Bond-Lader mood scales, was elevated at the earliest time points by the lowest dose, whilst "alertness" was significantly reduced at all time points following the highest dose. Both nicotinic and muscarinic binding were found to be low in comparison to the levels found in previous studies.

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Pilar Rupérez, Oussama Ahrazem, and J. Antonio Leal


Fucus vesiculosus was sequentially extracted with water at 22 °C (fraction 1 (F1)) and 60 °C (F2), and with 0.1 M HCl (F3) and 2 M KOH (F4) at 37 °C. Soluble fractions (42.3% yield) were composed of neutral sugars (18.9-48 g/100 g), uronic acids (8.8-52.8 g/100 g), sulfate (2.4-11.5 g/100 g), small amounts of protein (<1-6.1 g/100 g), and nondialyzable polyphenols (0.1-2.7 g/100 g). The main neutral sugars were fucose, glucose, galactose, and xylose. Infrared (IR) spectra of the fractions showed absorption bands at 820-850 and 1225-1250 cm^-1 for sulfate. F1, F2, and F4 also exhibited an absorption band at 1425 cm^-1, due to uronic acids, and their IR spectra resembled that of alginate. F3 had an IR spectrum similar to that of fucoidan with an average molecular weight of 1.6 × 10⁶ Da, calculated by molecular exclusion high-performance liquid chromatography. The presence of fucose in this polysaccharide was confirmed by ¹H NMR spectroscopy. This fraction showed the highest potential to be antioxidant by the ferric reducing antioxidant power (FRAP) assay, followed by the alkali- and water-soluble fractions. Sulfated polysaccharides from edible seaweeds potentially could be used as natural antioxidants by the food industry.

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A.F. CORREIA¹, J.F.O. SEGOVIA², M.C.A. GONÇALVES³, V.L. DE OLIVEIRA¹, D. SILVEIRA¹, J.C.T. CARVALHO³, L.I.B. KANZAKI<sup>1

1</sup>Laboratory of Molecular Pharmacology, Faculty of Health Sciences, University of Brasília, Brasilia (DF Brazil)
²The Brazilian Agricultural Research Corporation, Rodovia Juscelino Kubitschek, Fazendinha, Macapá (AP Brazil)
³Laboratory of Drugs, Federal University of Amapá Campus Universitário Marco Zero do Equador, Jardim Marco Zero, Macapá (AP Brasil)

Antimicrobial resistance is asubject o f great concern in public health and also in the designing of strategies for current therapeutic protocols all over the world. New drugs, including those necessary for a reserve armamentarium and exhibiting less side effects deserve special attention. In rural areas, particularly in Brazil, a huge number of natural products, in different artisanal preparations, mainly from plants, have been used by traditional populations to cure diseases. Despite some of these plants have been studied, many of them are awaiting to have their compounds chemically characterized and investigated their pharmacodynamics properties. Further, as well known, the environment plays a crucial role in the metabolism of these plants, yielding different and varied molecular complexes depending on the period of collection, climate conditions, kind of soil and also the plant speciation. In this report, ethanol crude extract of 10 different botanical specimens from the Amazon region of Brazil, in the Amapa State, were screened for antibacterial activity of 7 clinical resistant microorganisms utilizing as control ATCC bacterial species by the Kirby-Bauer method. Plant extracts of Geissospermum argenteum, Uncaria guianensis, Brosimum acutifolium, Copaifera reticulate, Licania macrophylla, Ptycopetalum olacoides and Dalbergia subcymosa yielded activity against Staphylococcus aureus and Pseudomonas aeruginosa, both multidrug resistant, and Staphylococcus aureus ATCC strain.

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Bucci LR.


Herbs have been used throughout history to enhance physical performance, but scientific scrutiny with controlled clinical trials has only recently been used to study such effects. The following herbs are currently used to enhance physical performance regardless of scientific evidence of effect: Chinese, Korean, and American ginsengs; Siberian ginseng, mahuang or Chinese ephedra; ashwagandha; rhodiola; yohimbe; CORDYCEPS: fungus, shilajit or mummio; smilax; wild oats; Muira puama; suma (ecdysterone); Tribulus terrestris; saw palmetto berries; beta-sitosterol and other related sterols; and wild yams (diosgenin). Controlled studies of Asian ginsengs found improvements in exercise performance when most of the following conditions were true: use of standardized root extracts, study duration (>8 wk, daily dose >1 g dried root or equivalent, large number of subjects, and older subjects. Improvements in muscular strength, maximal oxygen uptake, work capacity, fuel homeostasis, serum lactate, heart rate, visual and auditory reaction times, alertness, and psychomotor skills have also been repeatedly documented. Siberian ginseng has shown mixed results. Mahuang, ephedrine, and related alkaloids have not benefited physical performance except when combined with caffeine. Other herbs remain virtually untested. Future research on ergogenic effects of herbs should consider identity and amount of substance or presumed active ingredients administered, dose response, duration of test period, proper experimental controls, measurement of psychological and physiologic parameters (including antioxidant actions), and measurements of performance pertinent to intended uses.

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Waynberg J, Brewer S.


This study investigated the possibility of an alternative to chemical medication in the treatment of sexual dysfunction in healthy women. The efficacy of a unique herbal formulation of Muira puama and Ginkgo biloba (Herbal vX) was assessed in 202 healthy women complaining of low sex drive. Various aspects of their sex life were rated before and after 1 month of treatment. Responses to self-assessment questionnaires showed significantly higher average total scores from baseline in 65% of the sample after taking the supplement. Statistically significant improvements occurred in frequency of sexual desires, sexual intercourse, and sexual fantasies, as well as in satisfaction with sex life, intensity of sexual desires, excitement of fantasies, ability to reach orgasm, and intensity of orgasm. Reported compliance and tolerability were good. These initial findings support the strong anecdotal evidence for the benefits of Herbal vX on the female sex drive. A double-blind study is planned to further research these results.

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Antunes E, Gordo WM, de Oliveira JF, Teixeira CE, Hyslop S, De Nucci G.


The effects of the Brazilian herbal medicine Catuama and each of its plant constituents (Paullinia cupana, Trichilia catigua, Zingiber officinalis and Ptychopetalum olacoides) were investigated on rabbit corpus cavernosum (RbCC) using a bioassay cascade. Catuama caused short-lived and dose-dependent relaxations (11% +/- 7%, 26% +/- 5% and 82% +/- 9%, at doses of 1, 3 and 10 mg, respectively). Neither the nitric oxide synthesis inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 10 microM) nor the soluble guanylate cyclase inhibitor ODQ (10 microM) significantly affected the Catuama-induced relaxations. Similarly, the selective ATP-dependent K(+) channel (K(ATP)) blocker glibenclamide (10 microM), the muscarinic receptor antagonist atropine (1 microM) and the voltage-dependent Na(+) channel blocker tetrodotoxin (1 microM) all failed to affect significantly the Catuama-induced relaxations. These results indicate that the relaxations induced by Catuama involve neither nitric oxide release nor K(ATP) channel activation. The extracts of P. cupana, Z. officinalis and P. olacoides caused short-lived and dose-dependent RbCC relaxations, whereas T. catigua evoked long-lasting relaxations which were occasionally preceded by a brief contractile effect. The extract of P. cupana was the most active in relaxing RbCC strips. The relaxations induced by all extracts were not significantly affected by L-NAME (10 microM). The infusion of ODQ (10 microM) had no significant effect on the P. cupana- and Z. officinalis-induced relaxations but reduced by >50% (p < 0.05) those evoked by P. olacoides and T. catigua. Incubations of RbCC with Catuama(10 mg/mL for 0.25 to 5 min) caused increases of cAMP levels (143% increase at 5 min of incubation). Incubations of RbCC with P. cupana extract (1 mg/mL) increased the cAMP levels by 200% whereas higher doses (10 and 100 mg/mL) caused smaller increases in the nucleotide levels (150% and 89%, respectively). The extracts of Z. officinalis and P. olacoides (same doses) caused smaller increases of the cAMP levels compared with the P. cupana extract, whereas T. catigua (1-100 mg) did not increase the levels of this nucleotide above the basal values. Our results show that of the four extracts assayed, P. cupana was the most effective, indicating that it is the main extract responsible for the relaxing effect of Catuama on rabbit cavernosal tissue. Copyright 2001 John Wiley & Sons, Ltd.

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Speisky H, Cassels BK.


Boldo (Peumus boldus Mol.), a Chilean tree traditionally employed in folk medicine and recognized as a herbal remedy in a number of pharmacopoeias, mainly for the treatment of liver ailments, has recently been the subject of increasing attention. Boldine, in particular, the major and most characteristic alkaloidal constituent of this plant species, now emerges as its most interesting active principle from the pharmacological viewpoint. The recent demonstration that boldine is an effective antioxidant in both biological and non-biological systems has opened up the perspective of a broad range of uses in medicine and industry. Given the toxicological data on this alkaloid, its antioxidative properties situate it as a potentially useful substance in many disease states featuring free-radical related oxidative injury. This review attempts to cover and discuss the studies conducted over the last four decades on the chemical and pharmacological properties of boldo and its main constituent.

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Vila R, Valenzuela L, Bello H, Montes M, Adzet T.

The composition and the antimicrobial activity of the essential oil from the leaves of Peumus boldus is investigated. Analyses of the oil obtained by hydrodistillation were carried out by GC and GC-MS using columns of two different stationary phases. Fractionation of the essential oil by column chromatography on silica gel was performed to improve identification of some constituents. More than 90% of the total oil (46 components) was identified, major constituents being monoterpenes (90.5%), among which limonene (17.0%), p-cymene (13.6%), 1.8-cineole (11.8%), and beta-phellandrene (8.4%) reached the highest percentages. Determination of the minimal bactericidal or fungicidal concentration against several microorganisms showed interesting activities towards Streptococcus pyogenes, Micrococcus sp., and Candida sp.

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Garrido A, Bannach R, Gotteland M, Speisky H.


Boldine, an aporphine alkaloid extracted from the leaves and bark of boldo (Peumus boldus Mol.), has been shown to exhibit strong free-radical scavenger and antioxidant properties. Here, we report the in vitro ability of boldine to protect intact red cells against the haemolytic damage induced by the free radical initiator 2, 2'-azobis-(2-amidinopropane) (AAPH). Boldine concentration-dependently prevented the AAPH-induced leakage of haemoglobin into the extracellular medium. Substantial and similar cyto-protective effects of boldine were observed whether the antioxidant was added 1 h prior to, or simultaneously with, the azo-compound. The delayed addition of boldine, by 1 h relative to AAPH, diminished but did not abolish its cytoprotective effect. However, negligible effects of boldine were observed after its addition to erythrocytes previously incubated with AAPH for 2 h. The data presented demonstrate that, in addition to its well-established antioxidant effects, boldine also displays time-dependently strong cytoprotective properties against chemically induced haemolytic damage. Copyright 2000 John Wiley & Sons, Ltd.

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Gotteland M, Espinoza J, Cassels B, Speisky H.


BACKGROUND: Boldo (Peumus boldus Molina) is a widely used medicinal plant. However, its physiological effects are not well known. Recent studies in animals showed that certain components of boldo relax smooth muscle and prolong intestinal transit. AIM: To assess the effects of a dry boldo extract on oro cecal transit time in normal humans. SUBJECTS AND METHODS: Twelve volunteers received 2.5 g of a dry boldo extract or a placebo (glucose) during two successive periods of four days. On the fourth day, 20 g of lactulose were administered and breath hydrogen was collected every 15 min. Oro cecal transit time was defined as the time in which breath hydrogen increased by 20 ppm over the fasting level. RESULTS: Oro cecal transit time was larger after dry boldo extract administration, compared to placebo (112.5 +/- 15.4 and 87 +/- 11.8 min respectively, paired t p < 0.05). CONCLUSIONS: Dry boldo extract prolongs oro cecal transit time, a possible explanation for its medicinal use

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Jang YY, Song JH, Shin YK, Han ES, Lee CS.


Increased oxidative stress has been suggested to be involved in the pathogenesis and progression of diabetic tissue damage. Several antioxidants have been described as beneficial for oxidative stress-associated diseases. Boldine ([s]-2,9-dihydroxy-1, 10-dimethoxyaporphine) is a major alkaloid found in the leaves and bark of boldo (Peumus boldus Molina), and has been shown to possess antioxidant activity and anti-inflammatory effects. From this point of view, the possible anti-diabetic effect of boldine and its mechanism were evaluated. The experiments were performed on male rats divided into four groups: control, boldine (100 mg kg(-1), daily in drinking water), diabetic [single dose of 80 mg kg(-1)of streptozotocin (STZ), i.p.] and diabetic simultaneously fed with boldine for 8 weeks. Diabetic status was evaluated periodically with changes of plasma glucose levels and body weight in rats. The effect of boldine on the STZ-induced diabetic rats was examined with the formation of malondialdehydes and carbonyls and the activities of endogenous antioxidant enzymes (superoxide dismutase and glutathione peroxidase) in mitochondria of the pancreas, kidney and liver. The scavenging action of boldine on oxygen free radicals and the effect on mitochondrial free-radical production were also investigated. The treatment of boldine attenuated the development of hyperglycemia and weight loss induced by STZ injection in rats. The levels of malondialdehyde (MDA) and carbonyls in liver, kidney and pancreas mitochondria were significantly increased in STZ-treated rats and decreased after boldine administration. The activities of mitochondrial manganese superoxide dismutase (MnSOD) in the liver, pancreas and kidney were significantly elevated in STZ-treated rats. Boldine administration decreased STZ-induced elevation of MnSOD activity in kidney and pancreas mitochondria, but not in liver mitochondria. In the STZ-treated group, glutathione peroxidase activities decreased in liver mitochondria, and were elevated in pancreas and kidney mitochondria. The boldine treatment restored the altered enzyme activities in the liver and pancreas, but not the kidney. Boldine attenuated both STZ- and iron plus ascorbate-induced MDA and carbonyl formation and thiol oxidation in the pancreas homogenates. Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner. The alkaloid significantly attenuated the production of superoxide anions, hydrogen peroxide and nitric oxide caused by liver mitochondria. The results indicate that boldine may exert an inhibitory effect on STZ-induced oxidative tissue damage and altered antioxidant enzyme activity by the decomposition of reactive oxygen species and inhibition of nitric oxide production and by the reduction of the peroxidation-induced product formation. Boldine may attenuate the development of STZ-induced diabetes in rats and interfere with the role of oxidative stress, one of the pathogeneses of diabetes mellitus.

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Manabe H, Sakagami H, Ishizone H, Kusano H, Fujimaki M, Wada C, Komatsu N, Nakashima H, Murakami T, Yamamoto N.


Pretreatment of mice with hot water and alkaline extracts of Catuaba casca (Erythroxylum catuaba Arr. Cam.) effectively protected them from lethal infection of Escherichia coli and Staphylococcus aureus. The extracts significantly inhibited both the human immunodeficiency virus (HIV)-induced cytopathic effect and the expression of HIV antigen in HIV-1HTLV-IIIB or HIV-2ROD infected human lymphotropic virus type I (HTLV-1) positive MT-4 cells. The 50% effective concentrations of the active fractions (21-263 micrograms/ml) were 1/4 - 1/43 of their 50% cytotoxic concentrations. Their anti-HIV activity was shown to be induced, at least in part, via the inhibition of HIV adsorption to the cells. The data suggest a medicinal potential of Catuaba extracts against opportunistic infection in HIV patients.

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P S Venkateswaran, I Millman, and B S Blumberg

Abstract
An aqueous extract of the plant Phyllanthus niruri inhibits endogenous DNA polymerase of hepatitis B virus and binds to the surface antigen of hepatitis B virus in vitro. The extract also inhibits woodchuck hepatitis virus (WHV) DNA polymerase and binds to the surface antigen of WHV in vitro. The extract, nontoxic to mice, was tested for antiviral activity in woodchucks (Marmota monax). In a trial using six long-term WHV-carrier woodchucks, five treated animals showed a faster decrease in woodchuck hepatitis virus surface antigen titer compared to one untreated control. In animals recently infected with WHV, the extract was effective when administered i.p. in three out of four animals in reducing and within 3-6 weeks eliminating both the surface antigen titer and DNA polymerase activity in serum. The treatment was discontinued after 10 weeks, and the treated animals have remained free of detectable markers of WHV for more than 45 weeks. In contrast, three untreated controls remained positive for both markers for WHV. One of the controls died after 8 weeks; the other two controls have remained positive for WHV markers for more than 45 weeks. In a third trial with long-term carriers, test animals treated subcutaneously with the extract for 12 weeks did not respond; but on switching the mode of administration to i.p., two out of the five animals showed a significant decrease in woodchuck hepatitis virus surface antigen titer compared to controls.

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Campos AH, Schor N.


We investigated the in vitro effect of an aqueous extract of Phyllanthus niruri L. on a model of CaOx crystal endocytosis by Madin-Darby canine kidney cells. The extract exhibited a potent and effective non-concentration-dependent inhibitory effect on the CaOx crystal internalization. This response was present even at very high (pathologic) CaOx concentrations and no P. niruri L.-induced toxic effect could be detected. Biochemical analysis of culture media containing P. niruri L. did not provide any clues for the elucidation of the cellular pathways affected by this natural product. Although further studies are necessary for a better understanding of the role of P. niruri L. in urolithiasis, our findings show that this natural product could be an attractive alternative for the treatment of urinary stones.

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Freitas, A. M., Schor, N., Boim, M. A.


Abstract:
Objective: To evaluate the effect of an aqueous extract of P. niruri (Pn), a plant used in folk medicine to treat lithiasis, on the urinary excretion of endogenous inhibitors of lithogenesis, citrate, magnesium, and glycosaminoglycans (GAGs). Materials and methods: The effect of chronic (42 days) administration of Pn (1.25 mg m-1 day-1, orally) was evaluated in a rat model of urolithiasis induced by the introduction of a calcium oxalate (CaOx) seed into the bladder of adult male Wistar rats. The animals were divided into four groups: a sham control (16 rats); a control+Pn (six); CaOx+water instead of Pn (14); and CaOx+Pn (22). Plasma and urine were collected after 42 days of treatment for biochemical analysis and the determination of urinary excretion of citrate, magnesium and GAGs. The animals were then killed and the calculi analysed. Results: The creatinine clearance or urinary and plasma concentrations of Na+, K+, Ca2+, oxalate, phosphate, and uric acid were unaffected by Pn or the induction of lithiasis. Treatment with Pn strongly inhibited the growth of the matrix calculus and reduced the number of stone satellites compared with the group receiving water. The calculi were eliminated or dissolved in some treated animals (three of 22). The urinary excretion of citrate and magnesium was unaffected by Pn treatment. However, the mean (SD) urinary concentration of GAGs was significantly lower in rats treated with CaOx+Pn, at 5.64 (0.86) mg/g creatinine, than when treated with CaOx+water, at 11.78 (2.21) mg/g creatinine. In contrast, the content of GAGs in the calculi was higher in the CaOx+Pn rats, at 48.0 (10.4) g/g calculus, than in the CaOx+water group, at 16.6 (9.6) g/g calculus. Conclusion: These results show that Pn has an inhibitory effect on crystal growth, which is independent of changes in the urinary excretion of citrate and Mg, but might be related to the higher incorporation of GAGs into the calculi.

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Braga FC, Wagner H, Lombardi JA, de Oliveira AB.


Plants from the Brazilian flora were evaluated for the inhibition of 5-lipoxygenase. The species were selected based on their traditional use and on a chemosystematic approach. In total, 19 species belonging to 13 families have been investigated. Hedychium coronarium J. Koenig (Zingiberaceae), Xylopia frutescens Aubl. (Annonaceae) and Hymenaea courbaril L. (Leguminosae) presented a high 5-lipoxygenase inhibitory activity. Some hypothesis about the nature of the active compounds are discussed, based on reports of the chemical constitution of these species or other species from the same botanical family.

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Onusic GM, Nogueira RL, Pereira AM, Viana MB.


We investigated the effect of acute oral treatment with a water-alcohol extract of the inflorescence of Erythrina mulungu (EM, Leguminosae-Papilionaceae) (100, 200 and 400 mg/kg) on rats submitted to different anxiety models: the elevated T-maze (for inhibitory avoidance and escape measurements), the light/dark transition, and the cat odor test. These models were selected for their presumed capacity to demonstrate specific subtypes of anxiety disorders as recognized in clinical practice. Treatment with 200 mg/kg EM impaired avoidance latencies (avoidance 1 - 200 mg/kg EM: 18 +/- 7 s, control group: 40 +/- 9 s; avoidance 2 - 200 mg/kg EM: 15 +/- 4 s, control group: 110.33 +/- 38 s) in a way similar to the reference drug diazepam (avoidance 1: 3 +/- 0.79 s; avoidance 2: 3 +/- 0.76 s), without altering escape. Additionally, the same treatments increased the number of transitions (200 mg/kg EM: 6.33 +/- 0.90, diazepam: 10 +/- 1.54, control group: 2.78 +/- 0.60) between the two compartments and the time spent in the lighted compartment in the light/dark transition model (200 mg/kg EM: 39 +/- 7 s; diazepam: 61 +/- 9 s; control group: 14 +/- 4 s). The dose of 400 mg/kg EM also increased this last measurement (38 +/- 8 s). These results were not due to motor alterations since no significant effects were detected in the number of crossings or rearings in the arena. Furthermore, neither EM nor diazepam altered the behavioral responses of rats to a cloth impregnated with cat odor. These observations suggest that EM exerts anxiolytic-like effects on a specific subset of defensive behaviors, particularly those that have been shown to be sensitive to low doses of benzodiazepines.

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F. G. Gonzalez, T. Y. Portela, E. J. Stipp and L. C. Di Stasi


Abstract: Maytenus aquifolium (Celastraceae), Sorocea bomplandii (Moraceae) and Zolernia ilicifolia (Fabaceae) are native plants from the Tropical Atlantic Forest (Mata Atlântica, Brazil) known a ‘espinheira-santa’. These plants are traditionally used as analgesic and antiulcerogenic medicine, with the same traditional uses of the true ‘espinheira-santa’ (Maytenus ilicifolia, Celastraceae), an efficient antiulcerogenic agent. Pharmacological and toxicological studies with these plants have not been carried out. The purpose in this study was to evaluate the efficacy (analgesic and antiulcerogenic activities), safety (acute toxicity) and quality (phytochemical profile) of these three plants. The analgesic effect was analyzed by writhing and tail flick tests, while antiulcerogenic effect was performed through ulcer induction by ethanol and indomethacin/bethanecol assays. LD50 and acute toxic effects, as well as phytochemical profiles of all plants also were carried. Surprisingly, the three plants showed analgesic and antiulcerogenic effects at dose of 1000 mg/kg, v.o. Maytenus aquifolium lowering all ulcerogenic parameters (ethanol test), but increased the ulcerogenic effects in the indomethacin/bethanecol test. Sorocea bomplandii produced antiulcerogenic effects in both experimental models used, while Zolernia ilicifolia showed significant effects only in indomethacin/bethanecol-induced gastric lesions. Pre-treatment with Zolernia ilicifolia induced someone toxic effects. A phytochemical profile for each plant species was determined and its main chemical classes of compounds were described.

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Pepato MT, Keller EH, Baviera AM, Kettelhut IC, Vendramini RC, Brunetti IL.


The effects of using Bauhinia forficata leaf decoction (150 g leaf/l water; 35.2+/-7.8 ml/100 g body weight mean daily dose) as a drinking-water substitute for about 1 month on streptozotocin-diabetes (STZ-diabetes) in male Wistar rats were investigated. The physico-metabolic parameters measured were: body weight, food and liquid intake, urinary volume, hepatic glycogen, serum triglycerides and cholesterol, plasma glucose, urinary glucose and urea, and the weight of epididymal and retroperitoneal adipose tissue and soleus and extensor digitorum longus muscles. The STZ-diabetic rats treated with decoction showed a significant reduction in serum and urinary glucose and urinary urea as compared to the STZ-diabetic control, no difference being seen between decoction-treated and -untreated non-diabetic rats. The other physico-metabolic factors showed no changes in treated STZ-diabetic rats. The improvement in carbohydrate metabolism seen in the rats treated with Bauhinia forficata decoction does not appear to be linked to the inhibition of glycogenolysis or the stimulation of glycogenesis nor does it appear to act in a way similar to insulin or the sulfonylureas, although it may act by the inhibition of neoglycogenesis in a manner similar to that of the biguanides.

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Fábio Guilherme Gonçalves de Miranda, Jeane Carvalho Vilar, Ivana Andréa Nunes Alves , Sócrates Cabral de Holanda Cavalcanti and Ângelo Roberto Antoniolli


Background: Tabebuia avellanedae is a tree from the Bignoniaceae family. Commonly know as "pau d'arco" in Brazil, its inner bark is used as analgesic, anti-inflammatory, antineoplasic [1,2] and diuretic at the Brazilian northeast. Its anti-inflammatory, antimicrobial, and antineoplasic activities are cited in the literature as promoted by saponines, flavonoides, cumarines, and natural antibiotics, such as the lapachol and its derivatives encountered on its constituents [3-6]. The antifungal activity of aqueous, dichloromethane and methanol extracts from T. avellanedae and other 13 Paraguayan plants were accessed by Portillo et al. [7]. The aqueous and methanol extracts of T. avellanedae showed the highest antifungal activity. Phytochemical studies revealed the presence of naphthoquinones, anthraquinones and quinoid compounds in T. avellanedae, although lapachol, previously cited as anti-inflammatory [8], was not detected in its aqueous extract [9]. Since T. avellanedae inner bark is extensively used as analgesic in Brazil, the goal of our work was to describe the antiedematogenic and antinociceptive effects and acute toxicity of T. avellanedae inner bark aqueous extract on various animal models.

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Binutu OA, Lajubutu BA.


The methanol extracts of the leaves and stem bark of four Bignoniaceae plants Jacaranda mimosifolia D. Dol., Tecoma stans Linn., Tabebuia rosea (Bertol) D.C., and Crescentia cujete Linn. were studied for their antimicrobial activity using a wide range of Gram-positive and Gram-negative bacteria and fungi. Extracts of both the leaves and stem bark of majority of plant species studied showed variable but remarkable broad spectrum antimicrobial activity. However, methanol extracts of Tecoma stans leaves was found to be effective against only Candida albicans at the concentrations employed. It was observed that the extracts of stem bark generally showed better antimicrobial activity than those of the leaves and some organisms were selectively more sensitive to the extracts than others. Preliminary phytochemical screening of these plants revealed the presence of tannins, flavonoids, alkaloids, quinones and traces of saponins. The antimicrobial activity observed are discussed in relation to the chemical constituents reportedly isolated from these plants and their traditional uses.

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Spirling LI, Daniels IR.


Throughout history different species of mint have been used across the globe for their varying properties, both medicinal and culinary. Today, the commercial sales of mints are expanding each year--and at the end of a large meal after-dinner mints are frequently served. But why do we take them? Peppermint (Mentha piperita) is usually taken after a meal for its ability to reduce indigestion and colonic spasms by reducing the gastrocolic reflex. It is a naturally occurring hybrid cross between water mint (M. aquatica) and spearmint (M. spicata) and is best known for its role as a popular flavouring agent. Less well recognised is peppermint's potential role in the management of numerous other medical conditions including certain procedures, e.g. colonoscopy. With the growing popularity of herbal remedies, among both the public and medical practitioners, it would seem that now is an opportune time to consider further what peppermint has to offer the world of medicine.

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Ushid K, Maekawa M, Arakawa T.


Volatile sulfur compounds (VS) are generated in the large intestine by the bacterial metabolism of sulfate and sulfur amino acids. VS are potentially harmful to the host. The effect of dietary supplementation of herb extracts on volatile sulfur production in the large intestine of pig was evaluated in this study. The extracts Perilla frutescens (Soyou), Mentha piperita (Peppermint), and Ajuga decumbens (Kiransou) were fed to pigs equipped with a permanent cannula at the cecum. Cecal digesta were sampled and analyzed for ammonia and short-chain fatty acids (SCFA). Sampled digesta were incubated anaerobically either with or without L-methionine for 24 h to estimate volatile sulfur production in vivo. L-Methionine was supplemented to enhance methanethiol (MeSH) production. At the end of the incubation, head space concentrations of volatile sulfur compounds such as hydrogen sulfide (H2S), MeSH, and dimethyl sulfide (DMS) were determined by flame-photometric gaschromatography after the addition of 6 N HCl. Sampled digesta were also subjected to the most probable number estimations for sulfate-reducing bacteria (SRB), sulfide producer from L-methionine, and MeSH producers from L-methionine. All three herb extracts significantly decreased H2S (p<0.05), MeSH (p<0.05), and ammonia (p<0.05) production, but SCFA production was not affected (p>0.05). The number of volatile sulfur-producing bacteria did not vary among groups by the dietary supplementation of these herb extracts. Serial solvent extraction was done on these herb extracts to specify the active fractions that reduce volatile sulfur production. n-Butanol fraction of all three extracts significantly reduced volatile sulfur production in vitro.

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Iscan G, Kirimer N, Kürkçüoglu M., Baser KH, Demirci F.


Essential oils of peppermint Mentha piperita L. (Lamiaceae), which are used in flavors, fragrances, and pharmaceuticals, were investigated for their antimicrobial properties against 21 human and plant pathogenic microorganisms. The bioactivity of the oils menthol and menthone was compared using the combination of in vitro techniques such as microdilution, agar diffusion, and bioautography. It was shown that all of the peppermint oils screened strongly inhibited plant pathogenic microorganisms, whereas human pathogens were only moderately inhibited. Chemical compositions of the oils were analyzed by GC and GC/MS. Using the bioautography assay, menthol was found to be responsible for the antimicrobial activity of these oils.

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Jeppesen PB, Gregersen S, Alstrup KK, Hermansen K.


Extracts of leaves from the plant Stevia rebaudiana Bertoni have been used in the traditional treatment of diabetes in Paraguay and Brazil. Recently, we demonstrated a direct insulinotropic effect in isolated mouse islets and the clonal beta cell line INS-1 of the glycoside stevioside that is present in large quantity in these leaves. Type 2 diabetes is a chronic metabolic disorder that results from defects in both insulin and glucagon secretion as well as insulin action. In the present study we wanted to unravel if stevioside in vivo exerts an antihyperglycaemic effect in a nonobese animal model of type 2 diabetes. An i.v. glucose tolerance test (IVGT) was carried out with and without stevioside in the type 2 diabetic Goto-Kakizaki (GK) rat, as well as in the normal Wistar rat. Stevioside (0.2 g/kg BW) and D-glucose (2.0 g/kg BW) were administered as i.v. bolus injections in anaesthetized rats. Stevioside significantly suppressed the glucose response to the IVGT in GK rats (incremental area under the curve (IAUC): 648 +/- 50 (stevioside) vs 958 +/- 85 mM x 120 min (control); P < 0.05) and concomitantly increased the insulin response (IAUC: 51116 +/- 10967 (stevioside) vs 21548 +/- 3101 microU x 120 min (control); P < 0.05). Interestingly, the glucagon level was suppressed by stevioside during the IVGT, (total area under the curve (TAUC): 5720 +/- 922 (stevioside) vs 8713 +/- 901 pg/ml x 120 min (control); P < 0.05). In the normal Wistar rat stevioside enhanced insulin levels above basal during the IVGT (IAUC: 79913 +/- 3107 (stevioside) vs 17347 +/- 2882 microU x 120 min (control); P < 0.001), however, without altering the blood glucose response (IAUC: 416 +/- 43 (stevioside) vs 417 +/- 47 mM x 120 min (control)) or the glucagon levels (TAUC: 5493 +/- 527 (stevioside) vs 5033 +/- 264 pg/ml x 120 min (control)). In conclusion, stevioside exerts antihyperglycaemic, insulinotropic, and glucagonostatic actions in the type 2 diabetic GK rat, and may have the potential of becoming a new antidiabetic drug for use in type 2 diabetes.

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Chan P, Tomlinson B, Chen YJ, Liu JC, Hsieh MH, Cheng JT.


AIMS: Stevioside is a natural plant glycoside isolated from the plant Stevia rebaudiana which has been commercialized as a sweetener in Japan for more than 20 years. Previous animal studies have shown that stevioside has an antihypertensive effect. This study was to designed to evaluate the effect of stevioside in human hypertension. METHODS: A multicentre, randomized, double-blind, placebo-controlled study was undertaken. This study group consisted of 106 Chinese hypertensive subjects with diastolic blood pressure between 95 and 110 mmHg and ages ranging from 28 to 75 years with 60 subjects (men 34, women 26; mean +/- s.d., 54.1+/-3.8 years) allocated to active treatment and 46 (men 19, women 27; mean +/- s.d., 53.7+/-4.1 years) to placebo treatment. Each subject was given capsules containing stevioside (250 mg) or placebo thrice daily and followed-up at monthly intervals for 1 year. RESULTS: After 3 months, the systolic and diastolic blood pressure of the stevioside group decreased significantly (systolic: 166.0+/-9.4-152.6+/-6.8 mmHg; diastolic: 104.7 +/- 5.2-90.3+/-3.6 mmHg, P<0.05), and the effect persisted during the whole year. Blood biochemistry parameters including lipid and glucose showed no significant changes. No significant adverse effect was observed and quality of life assessment showed no deterioration. CONCLUSIONS: This study shows that oral stevioside is a well tolerated and effective modality that may be considered as an alternative or supplementary therapy for patients with hypertension.

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Hsu YH, Liu JC, Kao PF, Lee CN, Chen YJ, Hsieh MH, Chan P.


BACKGROUND: Stevioside is a natural sweet-tasting glycoside isolated from the herb Stevia rebaudiana, composed of stevia, a diterpenic carboxylic alcohol with three glucose molecules, mainly used commercially as sugar substitute. Previous study has shown that it can lower blood pressure in anesthetized spontaneously hypertensive rats (SHR). This study was undertaken to evaluate the antihypertensive effect of stevioside in different strains of hypertensive rats and to observe whether there is difference in blood pressure lowering effect. METHODS: Noninvasive tail-cuff method was employed to measure blood pressure. Stevioside at the concentrations of 50, 100 and 200 mg/kg were administered intraperitoneally (ip) to normotensive Wistar-Kyoto rats (NTR), SHR, deoxycorticosterone acetate-salt (DOCA-NaCl) sensitive hypertensive rats (DHR) and renal hypertensive rats (RHR). RESULTS: Significant hypotensive effect of stevioside administered ip was noted in different strains of rats at the dose of 50 mg/kg. When stevioside was increased to the concentrations of 100 and 200 mg/kg, ip, it also caused slow and persistent lowering of blood pressure in SHR and NTR. Data also showed that stevioside given at the concentrations of 100, 200 and 400 mg/kg ip resulted in lowering of blood pressure in SHR dose-dependently. Blood pressure returned to previous levels after the drug was discontinued for 2-3 days. Drinking of 0.1% stevioside solution in mature SHR could have antihypertensive effect and also prevented hypertension in immature SHR. CONCLUSIONS: This study reconfirmed stevioside has hypotensive effect and the effect is more prominent in hypertensive rats.

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Lee CN, Wong KL, Liu JC, Chen YJ, Cheng JT, Chan P.


Stevioside is a sweet-tasting glycoside occurring abundantly in the leaves of Stevia rebaudiana (Compositae). It has been used popularly in Japan and Brazil as a sugar substitute for decades. Previous study has shown that it lowered blood pressure in spontaneously hypertensive rats (SHRs) when administered intravenously. This study shows that intraperitoneal injection of stevioside 25 mg/kg also has antihypertensive effect in SHRs. In isolated aortic rings from normal rats, stevioside could dose-dependently relax the vasopressin-induced vasoconstriction in both the presence and absence of endothelium. However, stevioside had no effect on phenylephrine- and KCl-induced phasic vasoconstriction. In addition, stevioside lost its influence on vasopressin-induced vasoconstriction in Ca(2+)-free medium. The results indicate that stevioside caused vasorelaxation via an inhibition of Ca(2+) influx into the blood vessel. This phenomenon was further confirmed in cultured aortic smooth muscle cells (A7r5). Using 10(-5) M methylene blue for 15 min, stevioside could still relax 10(-8) M vasopressin-induced vasoconstriction in isolated rat aortic rings, showing that this vasorelaxation effect was not related to nitric oxide. The present data show that the vasorelexation effect of stevioside was mediated mainly through Ca(2+) influx inhibition.

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Takahashi K, Matsuda M, Ohashi K, Taniguchi K, Nakagomi O, Abe Y, Mori S, Sato N, Okutani K, Shigeta S.


Anti-human rotavirus (HRV) activity of hot water extracts from Stevia rebaudiana (SE) was examined. SE inhibited the replication of all four serotypes of HRV in vitro. This inhibitory effect of SE was not reduced on the prior exposure of SE to HCl for 30 min at pH 2. Binding assay with radiolabeled purified viruses indicated that the inhibitory mechanism of SE is the blockade of virus binding. The SE inhibited the binding of anti-VP7 monoclonal antibody to HRV-infected MA104 cells. The inhibitory components of SE were found to be heterogeneous anionic polysaccharides with different ion charges. The component analyses suggested that the purified fraction named as Stevian with the highest inhibitory activity consists of the anionic polysaccharide with molecular weight of 9800, and contains Ser and Ala as amino acids. Analyses of sugar residues suggest uronic acid(s) as sugar components. It did not contain amino and neutral sugars and sulfate residues. These findings suggest that SE may bind to 37 kD VP7 and interfere with the binding of VP7 to the cellular receptors by steric hindrance, which results in the blockade of the virus attachment to cells.

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Arletti R, Benelli A, Cavazzuti E, Scarpetta G, Bertolini A.


Sexually potent and sexually sluggish/impotent male rats were treated orally with different amounts of Turnera diffusa and Pfaffia paniculata fluid extracts (0.25, 0.50, 1.0 ml/kg). While having no effect on the copulatory behavior of sexually potent rats, both plant extracts--singly or in combination--improved the copulatory performance of sexually sluggish/impotent rats. The highest dose of either extract (1 ml/kg) (as well as the combination of 0.5 ml/kg of each extract) increased the percentage of rats achieving ejaculation and significantly reduced mount, intromission and ejaculation latencies, post-ejaculatory interval and intercopulatory interval. Neither extract affected locomotor activity. These results seem to support the folk reputation of Turnera diffusa and Pfaffia paniculata as sexual stimulants.

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Watanabe T, Watanabe M, Watanabe Y, Hotta C.


Pfaffia paniculata (Brazilian ginseng) administered subcutaneously and intraperitoneally inhibits growth of allogeneic cancer cells in mice. The goal of this study was to determine whether oral administration of P. paniculata inhibits development of spontaneous leukemia. Four-week-old female AKR/J mice were given oral doses of powdered roots from P. paniculata three times weekly for 8 weeks; controls received phosphate-buffered saline. Enlargement of thymic lymphoma in the mice treated with P. paniculata was significantly suppressed, as compared with controls (128 +/- 67.3 mg versus 219.9 +/- 84.2 mg, respectively; P < .01); proliferation of endogenous recombinant murine leukemia viruses (MuLV) in the thymus was markedly inhibited after the first oral treatment as compared with untreated controls (final age, 28 weeks; P < .05). In normal 3-week-old female AKR/J mice, mortality from thymic lymphoma was delayed markedly after injection into the thymus of cell-free extract of thymus from the experimental female 28-week-old AKR/J mice that received the oral P. paniculata preparation. These results suggest that the agent's suppressive effects on spontaneously occurring leukemia caused by endogenous recombinant MuLV in female AKR/J mice may depend on enhancement of nonspecific immune or cellular immune systems (or both) by the P. paniculata preparation.

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Huguet AI, Máñez S, Alcaraz MJ.


The superoxide anion scavenging activity of 38 flavonoids, some of them isolated from Sideritis mugronensis, Sideritis javalambrensis and Cayaponia tayuya were investigated by measurement of their inhibition of nitroblue tetrazolium reduction. Isoorientin, orientin, amentoflavone, leucocyanidol, eriodictyol, datiscetin and robinetin behaved as potent scavengers and structure-activity relationships were established.

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Lemaire I, Assinewe V, Cano P, Awang DV, Arnason JT.


Two extracts of different collections of the traditional medicine uña de gato (Uncaria tomentosa) from Peru were characterized by High Pressure Liquid Chromatography as containing approximately 6 mg/g total oxindole content prior to studies with alveolar macrophages. The plant preparations greatly stimulated IL-1 and IL-6 production by rat macrophages in a dose dependent manner in the range of 0.025-0.1 mg/ml. They were also able to enhance IL-1 and -6 in lipopolysaccharide-stimulated macrophages. The results suggest a strong immunostimulant action of this plant.

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Sandoval M, Charbonnet RM, Okuhama NN, Roberts J, Krenova Z, Trentacosti AM, Miller MJ.


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.

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Mur E, Hartig F, Eibl G, Schirmer M.


OBJECTIVE: To evaluate safety and clinical efficacy of a plant extract from the pentacyclic chemotype of Uncaria tomentosa (UT) in patients with active rheumatoid arthritis (RA). METHODS: Forty patients undergoing sulfasalazine or hydroxychloroquine treatment were enrolled in a randomized 52 week, 2 phase study. During the first phase (24 weeks, double blind, placebo controlled), patients were treated with UT extract or placebo. In the second phase (28 weeks) all patients received the plant extract. RESULTS: Twenty-four weeks of treatment with the UT extract resulted in a reduction of the number of painful joints compared to placebo (by 53.2% vs 24.1%; p = 0.044). Patients receiving the UT extract only during the second phase experienced a reduction in the number of painful (p = 0.003) and swollen joints (p = 0.007) and the Ritchie Index (p = 0.004) compared to the values after 24 weeks of placebo. Only minor side effects were observed. CONCLUSION: This small preliminary study demonstrates relative safety and modest benefit to the tender joint count of a highly purified extract from the pentacyclic chemotype of UT in patients with active RA taking sulfasalazine or hydroxychloroquine.

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Lamm S, Sheng Y, Pero RW.


A human intervention study was carried out using male volunteers attending a General Practice Clinic in New York City involving comparison of individuals supplemented with 350 mg x 2 C-Med-100 daily dose for two months with untreated controls for their abilities to respond to a 23 valent pneumococcal vaccine. C-Med-100 is a novel nutraceutical extract from the South American plant Uncaria tomentosa or Cat's Claw which is known to possess immune enhancing and antiinflammatory properties in animals. There were no toxic side effects observed as judged by medical examination, clinical chemistry and blood cell analysis. However, statistically significant immune enhancement for the individuals on C-Med-100 supplement was observed by (i) an elevation in the lymphocyte/neutrophil ratios of peripheral blood and (ii) a reduced decay in the 12 serotype antibody titer responses to pneumococcal vaccination at 5 months.

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Klaus Keplinger^a, Gerhard Laus^a, Martin Wurm^b, Manfred P. Dierich^b and Herwig Teppner^c

Abstract
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 uña 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.