Pharmacological and Toxicological Study of Maytenus ilicifolia Leaf Extract Part II-Clinical Study (Phase I).

Maytenus ilicifolia is a plant widely used in South American folk medicine as an effective anti-dyspeptic agent, and the aim of this study was to evaluate their clinical and toxicological effects in healthy volunteers in order to establish its maximum safe dose. We selected 24 volunteers (12 women and 12 men) between 20 and 40 years of age and put them through clinical/laboratory screening and testing to ascertain their psychomotor functions (simple visual reaction, speed and accuracy, finger tapping tests). M. ilicifolia tablets were administered in increasing weekly dosages, from an initial dose of 100 mg to a final dose of 2000 mg. The volunteers' clinical and biochemical profiles and psychomotor functions were evaluated weekly, and they also completed a questionnaire about any adverse reactions. All subjects completed the study without significant changes in the evaluated parameters. The most cited adverse reactions were xerostomia (dry mouth syndrome) (16.7%) and polyuria (20.8%), with reversal of these symptoms without any intervention during the study. The clinical Phase I study showed that the administration of up to 2000 mg of the extract was well tolerated, with few changes in biochemical, hematological or psychomotor function parameters, and no significant adverse reactions. Copyright © 2017 John Wiley & Sons, Ltd.

Are medicinal herbs safe? The opinion of plant vendors from Diadema (São Paulo, southeastern Brazil)

Medicinal plants (MP) have been used world-wide for the treatment or prevention of health conditions and due to their natural origin; they have been historically considered harmless. Semi-structured interviews were carried out with an intentional sample of twenty plant vendors in the city of Diadema to explore their knowledge and beliefs on the safety and efficacy of MP. Different levels of perceptions about the safety of MP were found, varying from "completely safe" to "completely harmful". The majority of the interviewees declared that "if herbs have an effect, they are also likely to have a side effect", depending on many factors such as dosage, concomitant use of other drugs, characteristics of the plant material and consumer related factors, specially those related to pregnant women, children and elderly people. Thirty-nine unexpected events related to 21 species of MP were reported. One case of serious gastrointestinal disease related to the consumption of a contaminated "slim mixture" was also described. Adverse events and other problems that result from MP are relatively uncommon, but they are almost certainly underreported and occur more often than acknowledged. This study strengthens the call for further research and educational efforts into this complex area.

Preclinical toxicological assessment of a phytotherapeutic product--CPV (based on dry extracts of Crataegus oxyacantha L., Passiflora incarnata L., and Valeriana officinalis L.).

Associations of plants have been widely used, for centuries, in Ayurveda and in Chinese medicine and have been increasingly acknowledged in Western medicine. The objective of this study is to assess the level of toxicity of an association of three plants: Crataegus oxyacantha, Passiflora incarnata, and Valeriana officinalis (CPV extract). This association was administered to rats, mice, and dogs, both acute and chronically for 180 days. The tests used in the acute experiments were: observational pharmacological screening, LD(50), motor coordination and motor activity. Chronic tests carried out were: weight gain/loss and behavioral parameters in rats and in mice; estrus cycle, effects on fertility, and teratogenic studies in rats and of mutagenic features in mice, in addition to the Ames test. The following parameters were assessed in dogs: weight gain/loss, general physical conditions, water/food consumption and anatomopathological examination of the organs subsequent to the 180 days of treatment. All of the results were negative, showing that CPV administered in high doses and over a long period of time presents no toxicity, suggestive of the fact that this is an association devoid of risk for human beings.

Evaluation of Baccharis trimera and Davilla rugosa in tests for adaptogen activity.

Baccharis trimera (Asteraceae) and Davilla rugosa (Dilleniaceae) are used popularly as tonics, aphrodisiacs and for stomach ailments, among other uses. Hydroalcohol extracts of the aerial parts of both plants were investigated with regard to their chemical constitution and their pharmacological activity in tests that evaluate adaptogen activity. Alkaloids, flavonoids, saponins, polyphenols/tannins and coumarins were identified in both extracts, while lignans were found only in the extract of Davilla rugosa. This extract presented also a marked antioxidant activity and exerted a moderate antiulcer effect in rats submitted to cold immobilization stress. It did not, however, inhibit the increase in the levels of ACTH and corticosterone induced by stress. Moreover, the Davilla rugosa did not improve the physical performance of mice submitted to forced exercise and the learning time of old rats in the T-maze, neither did it reduce the blood viscosity of the old animals. Conversely, the Baccharis trimera extract only presented a moderate antioxidant activity, without any positive effect on the other tests. These results point to the absence of an adaptogen activity of Baccharis trimera, with some effects that could be related to such an activity as regards the Davilla rugosa.

A comparison of plants utilized in ritual healing by two Brazilian cultures: Quilombolas and Kraho Indians.

The present study deals with two ethnobotanical surveys carried out in two different segments of the Brazilian population: the first among the Krahô Indians living in Tocantins State, a Cerrado region, and the second one among the descendants of former black slaves, the Quilombolas, living in Mato Grosso State. Both populations use plants which may have effects on the central nervous system (CNS) in their ritual healing ceremonies. Field work was performed during two years by one of the authors (E. Rodrigues) utilizing methods from botany and anthropology. Information was obtained on a total of 169 plants which were utilized in the preparation of 345 prescriptions for 68 ailments seemingly of the CNS, classified as tonics, analgesics, anorectics, hallucinogens, and anxiolytics. The taxonomic families of plants used, the more common therapeutic indications and types of healing rituals are discussed.

Plants with possible psychoactive effects used by the Krahô Indians, Brazil

OBJECTIVE: In spite of the richness of the Brazilian biodiversity, no phytomedicines have been developed from this flora with the purpose of being used in psychiatric treatments. The objective of the present study was to document the use of plants with possible psychoactive effects in rituals performed by the Krahô Indians, who live in the cerrado savannahs biome in the central region of Brazil. Also, the present data were compared with the data obtained during a review of the literature on the use of psychoactive plants by 25 Brazilian indigenous groups. METHOD: The study was carried out during two years of fieldwork during which anthropological and botanical methods were employed. RESULTS: Seven local shamans were interviewed and they indicated 98 formulas, consisting of 45 plant species that appear to have psychoactive properties and were used in 25 different treatments. Some of the psychoactive properties were "prevention of madness", "stimulant effect", "tranquilizing effect", "prevention of tremors", "longer sleeping period", "open mind" and "induction of sleep". This article also describes the review of literature, which recorded 58 plants that may have psychoactive effects used by 25 Brazilian Indian cultures. CONCLUSION: The treatment of psychological/psychiatric disorders based on the plants used by the Krahô Indians is very rich. It is also observed among other Brazilian indigenous groups. Future phytochemical and pharmacological studies on these plants may develop new medicines to treat psychiatric disorders.

OBJETIVO: Apesar da riqueza da biodiversidade brasileira, não foram desenvolvidos, até o momento, fitoterápicos voltados para tratamentos psiquiátricos a partir desta flora. O principal objetivo deste estudo é documentar as plantas utilizadas pelos índios Krahô em rituais de cura, sobretudo aquelas com potenciais ações psicoativas. Esta etnia indígena ocupa uma área no bioma cerrado, numa região central do Brasil. Além disso, estes resultados foram comparados àqueles obtidos durante um levantamento bibliográfico realizado a respeito das plantas psicoativas utilizadas por outras 25 etnias indígenas brasileiras. MÉTODO: Os dois anos de trabalho de campo foram conduzidos utilizando-se métodos da antropologia e botânica. RESULTADOS: Sete xamãs locais foram entrevistados e indicaram 98 receitas preparadas a partir de 45 plantas para 25 usos, que parecem estar envolvidos a propriedades psicoativas. São eles: "para evitar ficar louco", "estimulante", "calmante", "para diminuir tremores", "para dormir por mais tempo", "para abrir a cabeça" e "para induzir o sono". Este artigo descreve também um levantamento bibliográfico que registrou 58 plantas utilizadas por 25 etnias indígenas brasileiras que, de modo similar, podem ter alguma ação psicoativa. CONCLUSÃO: É muito rica a terapêutica para males psicológicos/psiquiátricos a partir de plantas utilizadas pelos índios Krahô. Este mesmo fato ocorre entre outras etnias indígenas brasileiras. Futuros estudos de fitoquímica e farmacologia a serem realizados com estas plantas poderão prover a psiquiatria com novos medicamentos.

Plants with possible psychoactive effects used by the Krahô Indians, Brazil.

OBJECTIVE: In spite of the richness of the Brazilian biodiversity, no phytomedicines have been developed from this flora with the purpose of being used in psychiatric treatments. The objective of the present study was to document the use of plants with possible psychoactive effects in rituals performed by the Krahô Indians, who live in the cerrado savannahs biome in the central region of Brazil. Also, the present data were compared with the data obtained during a review of the literature on the use of psychoactive plants by 25 Brazilian indigenous groups. METHOD: The study was carried out during two years of fieldwork during which anthropological and botanical methods were employed. RESULTS: Seven local shamans were interviewed and they indicated 98 formulas, consisting of 45 plant species that appear to have psychoactive properties and were used in 25 different treatments. Some of the psychoactive properties were "prevention of madness", "stimulant effect", "tranquilizing effect", "prevention of tremors", "longer sleeping period", "open mind" and "induction of sleep". This article also describes the review of literature, which recorded 58 plants that may have psychoactive effects used by 25 Brazilian Indian cultures. CONCLUSION: The treatment of psychological/psychiatric disorders based on the plants used by the Krahô Indians is very rich. It is also observed among other Brazilian indigenous groups. Future phytochemical and pharmacological studies on these plants may develop new medicines to treat psychiatric disorders.

Use of South American plants for the treatment of neuropsychiatric disorders.

Two conditions greatly encourage the folk use of plants to cure diseases and alleviate ailments: plant biodiversity (the richer the better)particular cultural traits of local populations.

Ritual use of plants with possible action on the central nervous system by the Kraho Indians, Brazil.

The aim of the present study was to document the use of plants, probably acting on the central nervous system (CNS), in rituals carried out by the Kraho Indians, who occupy the cerrado biome in the central region of Brazil. The 2 years of fieldwork were guided by methods of anthropology and botany. The local shamans have indicated 286 formulas, consisting of 138 plant species in 50 uses that could be associated with some type of action on the CNS; of which 98 formulas, 87 plants and 25 uses, appear to involve psychoactive properties, such as: 'to get slow', 'stimulant effect', 'to calm down', 'to enhance memory', 'to reduce anxiety' and 'to induce sleep'. Phytochemical and pharmacological literature data were queried to establish any correlation between indigenous knowledge and scientific indications, for each one of the 138 plant species. Studies were available for 11 of these plants; and for two of them, scientific data coincided with indigenous information.

Plants used by a Quilombola group in Brazil with potential central nervous system effects.

This study focused on an ethnopharmacological survey among a group of Brazilian Quilombolas (descended from runaway slaves living in hideouts up-country) whose therapeutic practices involve a combination of healing ceremonies and prescription of medicinal plants consisting of the use of, at least, 48 plants with possible effect on the central nervous system (CNS), cited in 53 formulas prescribed for 17 therapeutic indications, the main ones being: to fortify the brain, for insomnia, as a sedative, for insanity, weight loss, and rejuvenation. The formulas consist of one to ten plants, and each plant may be recommended for up to seven different therapeutic indications, with evidence of non-specificity in the use of plants in this culture. Of these 48 plants, only 31 could be identified to the species level as belonging to 20 taxonomic families, with the Asteraceae, Malpighiaceae, Cyperaceae, and Myrtaceae as the most important families. Only eleven of these species have been previously studied and appear in scientific literature. Some of these plants are at present under study in the Department of Psychobiology of the Federal University of Sao Paulo.

Plants and the central nervous system.

This review article draws the attention to the many species of plants possessing activity on the central nervous system (CNS). In fact, they cover the whole spectrum of central activity such as psychoanaleptic, psycholeptic and psychodysleptic effects, and several of these plants are currently used in therapeutics to treat human ailments. Among the psychoanaleptic (stimulant) plants, those utilized by human beings to reduce body weight [Ephedra spp. (Ma Huang), Paullinia spp. (guaraná), Catha edulis Forssk. (khat)] and plants used to improve general health conditions (plant adaptogens) were scrutinized. Many species of hallucinogenic (psychodysleptic) plants are used by humans throughout the world to achieve states of mind distortions; among those, a few have been used for therapeutic purposes, such as Cannabis sativa L., Tabernanthe iboga Baill. and the mixture of Psychotria viridis Ruiz and Pav. and Banisteriopsis caapi (Spruce ex Griseb.) C.V. Morton. Plants showing central psycholeptic activities, such as analgesic or anxiolytic actions (Passiflora incarnata L., Valeriana spp. and Piper methysticum G. Forst.), were also analysed.Finally, the use of crude or semipurified extracts of such plants instead of the active substances seemingly responsible for their therapeutic effect is discussed.

Heteropterys aphrodisiaca (extract BST0298): a Brazilian plant that improves memory in aged rats.

Literature report is lacking on pharmacological studies of the plant Heteropterys aphrodisiaca, endemic to the scrublands of Brazil. The present study was carried out to investigate the effects of oral dosing with extract BST0298 from this plant, on learning and on memory, in young (3-6-month-old) and aged (20-28-month-old) rats. The aged animals presented significant memory deficits in both the passive avoidance and T-maze left/right discrimination tests. Treatment for 7 days (50 mg/kg) or 26 days (100 mg/kg) with extract BST0298 restored the memory deficits in the passive avoidance test. However, no improvement in memory was observed after acute administration of extract BST0298 (100 mg/kg) in aged rats. An improvement in learning was also observed in the left/right discrimination test in aged rats treated for 109 days with BST0298 at a dose of 50 mg/kg. These results suggest that treatment for 7 days or more with H. aphrodisiaca improves learning and memory deficits in aged rats.

Protective effect of oleuropein, an olive oil biophenol, on low density lipoprotein oxidizability in rabbits.

On the basis of the results obtained with pilot studies conducted in vitro on human low density lipoprotein (LDL) and on cell cultures (Caco-2), which had indicated the ability of certain molecules present in olive oil to inhibit prooxidative processes, an in vivo study was made of laboratory rabbits fed special diets. Three different diets were prepared: a standard diet for rabbits (diet A), a standard diet for rabbits modified by the addition of 10% (w/w) extra virgin olive oil (diet B), a modified standard diet for rabbits (diet C) differing from diet B only in the addition of 7 mg kg(-1) of oleuropein. A series of biochemical parameters was therefore identified, both in the rabbit plasma and the related isolated LDL, before and after Cu-induced oxidation. The following, in particular, were selected: (i) biophenols, vitamins E and C, uric acid, and total, free, and ester cholesterol in the plasma; (ii) proteins, triglycerides, phospholipids, and total, free, and ester cholesterol in the native LDL (for the latter, the dimensions were also measured); (iii) lipid hydroperoxides, aldehydes, conjugated dienes, and relative electrophoretic mobility (REM) in the oxidized LDL (ox-LDL). In an attempt to summarize the results obtained, it can be said that this investigation has not only verified the antioxidant efficacy of extra virgin olive oil biophenols and, in particular, of oleuropein, but has also revealed a series of thus far unknown effects of the latter on the plasmatic lipid situation. In fact, the addition of oleuropein in diet C increased the ability of LDL to resist oxidation (less conjugated diene formation) and, at the same time, reduced the plasmatic levels of total, free, and ester cholesterol (-15, -12, and -17%, respectively), giving rise to a redistribution of the lipidic components of LDL (greater phospholipid and cholesterol amounts) with an indirect effect on their dimensions (bigger by about 12%).

Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro.

The effects on toxic and behavioral levels of guarana (Paullinia cupana) were assessed in rats and mice subsequent to acute and chronic administrations and were compared to those produced by Ginseng (Panax ginseng). Experimental parameters included tests for antioxidant capacity in vitro and measured in vivo, toxicological screening, progress in weight, motor activity, death rate, and histopathological examination of the viscera. Guarana showed an antioxidant effect because, even at low concentrations (1.2 microg/ml), it inhibited the process of lipid peroxidation. In high doses of 1000-2000 mg/kg (i.p. and p.o.) it did not induce significant alterations in parameters for toxicological screening. No effects on motor activity were observed, neither did guarana alter the hypnotic effect of pentobarbital. Ginseng (250-1000 mg/kg i.p.), however, elicited reductions in motor activity, eyelid ptosis and bristling fur. Consumption of liquids containing guarana or ginseng and progress in weight of the animals remained at levels similar to the controls, even after prolonged administration. The percentage mortality was equivalent in control and in treated groups. The absence of toxicity of guarana was also demonstrated by histopathological examination, with no alteration being detected in heart, lungs, stomach, small and large intestine, liver, pancreas, kidneys, bladder and spleen.

Pharmacological activity of Guarana (Paullinia cupana Mart.) in laboratory animals.

Mice that ingested a suspension of guarana (Paullinia cupana, Sapindaceae) in a dose of 0.3 mg/ml showed a significant increase in physical capacity when subjected to a stressful situation such as forced swimming after 100 and 200 days of treatment. Such an effect, however, was not obtained with a concentration of 3.0 mg/ml, nor with the ingestion of a suspension of ginseng 5.0 mg/ml, nor of a solution of caffeine 0.1 mg/ml. Guarana, both after a single (3.0 and 30 mg/kg) or chronic administrations (0.3 mg/ml), was able to partially reverse the amnesic effect of scopolamine as measured through a passive avoidance test in mice and rats, indicating a positive effect on memory acquisition. However, no effect was observed when an active avoidance task was used in rats, even after 20 days of guarana administration. There was also a tendency of rats treated with 0.3 mg/ml of guarana to better maintain the memory of a Lashley III maze path. The animals had the same average lifespan, indicating a low toxicity of guarana, even after 23 months of treatment.

The effects of long-term administration of guarana on the cognition of normal, elderly volunteers.

Paulinia cupana (guarana) is a Brazilian plant given great prestige in popular medicine, for example as being a potent stimulator of brain functions. The authors assessed the effects of the long-term administration of guarana on the cognition of normal, elderly volunteers. Forty-five volunteers were studied, with a random distribution in three experimental groups: placebo (n = 15), caffeine (n = 15), and guarana (n = 15), in a double-blind study. There were no significant cognitive alterations in these volunteers.

Antiulcerogenic effects of two Maytenus species in laboratory animals.

Leaves of Maytenus species are commonly used in Brazil for the treatment of gastric ulcers, dyspepsias and other gastric problems. The present study evaluated the antiulcerogenic potential of a boiling water extract of equal parts of M. aquifolium and M. ilicifolia leaves against ulcer lesions induced by indomethacin and cold-restraint stress in rats. Ranitidine and cimetidine were used as reference drugs. The oral and intraperitoneal administration of the extract had a potent antiulcerogenic effect against both types of ulcers. The extract was shown to cause an increase in volume and pH of gastric juice of the animals with the pH effects comparable to those of cimetidine. The results tend to confirm the popular use of the plant.

Pharmacologic and toxicologic effects of two Maytenus species in laboratory animals.

Leaves of Maytenus species are used in the popular medicine of Brazil for their reported antacid and antiulcerogenic activity. The present work examined the effects of a boiling water extract of equal parts of M. aquifolium and M. ilicifolia leaves on acute administration in rats and mice, in an attempt to detect any general depressant, hypnotic, anticonvulsant and analgesic effects. General depressant and hypnotic effects were seen only after intraperitoneal administration. After chronic administration, the overall behavior of animals did not change and they continued to gain weight at the same rate as controls. Several biochemical and hematological parameters as well as pathological examination of different organs did not show any significant alterations after 3 months of treatment. A search for the potential effects of the extract on the fertility of female and male rats and on the course of pregnancy as well as a search for potential teratogenic effects did not reveal any significant differences from controls. Taken together, the results indicate that these Maytenus species may be safe for human use and deserve further investigation.

Estudo da eventual açäo antiúlcera gástrica do Bálsamo (Sedum Sp) Folha-de-Fortuna (Bryophyll umcalycinum) couve (Brassica oleraceae) e de Espinheira-Santa (Maytenus ilicifolia) em ratos / Study on the Possible Anti Gastric Ulcer Effect of Sedum Sp, Bryophyll umcalycinum, and Maytenus ilicifolia in Rats

Preparaçöes feitas destas plantas, seguindo as receitas populares, foram estudadas quanto aos possíveis efeitos protetores em ratos submetidos, experimentalmente, a quatro tipos de úlcera gástrica: por aspirina, indometacinam reserpina ou imobilizaçäo em baixa temperatura (4-C). Como substâncias-padräo para comparaçäo dos efeitos, utilizou-se também a rantidina, cimetidina e dois extratos de couve empregados na preparaçäo de medicamentos, sendo um deles importado da Europa. Como era de se esperar, a ranitidina e cimetidina conferiram marcante proteçäo aos ratos submetidos a qualquer dos métodos indutores de úlcera. As preparaçöes de folha-da fortuna e da couve, bem como os dois extratos-padräo da couve, foram totalmente inativos em todos os métodos empregados. Esta ausência de efeitos antiúlcera gástrica nos ratos ocorreu mesmo quando as preparaçöes foram dadas por via oral ou intraperitoneal por vários dias. Os efeitos do bálsamo foram pouco concludentes. Algumas experiências mostraram efeito protetor quando as úlceras foram induzidas por aspirina e reserpina, enquanto que, em outras experiências, näo se obteve proteçäo. Além disso, o bálsamo näo os protegeu contra as úlceras induzidas por indometacina ou imobilizaçäo em baixa temperatura. A espinheira-santa, ao contrário, revelou marcante efeito protetor de úlceras induzidas pelos métodos da indometacina, reserpina e imobilizaçäo em baixa temperatura. Este efeito, comparável ao da cimetidina, foi obtido tanto como abafado como com o liofilizado da planta, administrados por via oral ou intraperitoneal

Efeito protetor do liofilizado obtido do abafado de Maytenus Sp (espinheira-santa) contra úlcera gástrica experimental em ratos / Protection Effect of the Lyophilized Obtained from Dried Leaves of the Maytenus Sp. Against Experimental Gastric Ulcers in Rats

Cinco diferentes amostras de Maytenus sp (espinheira-santa), três delas a M. ilicifolia e duas a M. aquifolium revelaram potente efeito antiúlcera gástrica, quando utilizadas, por via i.p., sob a forma de liofilizados, obtidos a partir de abafados, em ratos submetidos aos processos de induçäo de úlcera por endometacina ou por stress de imobilizaçäo em baixa temperatura. O efeito portetor é dose-dependente, persiste no mínimo até 16 meses após a coleta da planta e é equiparável aos efeitos da cimetidina e ranitidina. Além da atividade antiúlcera, o liofilizado a espinheira-santa, a semelhança da cimetidina, aumentou grandemente o volume e o pH do conteúdo gástrico. Foi discutido se o efeito obtido com o liofilizado da espinheira-santa poderia ser devido a derivados tanínicos presentes no mesmo