Clinical References on Babassu (Orbignya sp)
Gaitan E, et al. Antithyroid effects in vivo and in vitro of babassu and mandioca: a staple food in goiter areas of Brazil. Eur J Endocrinol, 1994 Aug
(Abstract Available)
Silva CM, et al. [The coconut babaçu (Orbignya phalerata martins) as a probable risk of human infection by the agent of chromoblastomycosis in the State of Maranhão, Brazil] Rev Soc Bras Med Trop, 1995 Jan-Mar
(Abstract Available)
Bento DN, et al. [The epidemiology of Chagas' disease in a rural area of the city of Teresina, Piauí, Brazil] Rev Soc Bras Med Trop, 1992 Jan-Mar
Miles MA, et al. Chagas' disease in the Amazon basin: V. Periurban palms as habitats of
Rhodnius robustus and Rhodnius pictipes--triatomine vectors of Chagas' disease. Mem Inst Oswaldo Cruz, 1983 Oct-Dec
Check Medline for new articles.
Antithyroid effects in vivo and in vitro of babassu and mandioca: a staple food in goiter areas of Brazil.
Gaitan E; Cooksey RC; Legan J; Lindsay RH; Ingbar SH; Medeiros-Neto G
Eur J Endocrinol, 131: 2, 1994 Aug, 138-44
Babassu (Orbignya phalerata), a palm-tree coconut fruit, mixed with mandioca (Manihot
utilissima) is the staple food of people living in the endemic goiter area of Maranhao in Brazil, where goiter prevalence among schoolchildren was still 38% in 1986 despite an adequate iodine intake in most of the population. Therefore, the question arose as to whether or not the ingestion of babassu alone or mixed with mandioca contributed to the persistence of endemic goiter in this area of Brazil. In this investigation we examined the potential antithyroid effects of babassu and mandioca by means of in vivo studies in Sprague-Dawley rats, in vitro studies in porcine thyroid slices and using a purified porcine thyroid peroxidase (TPO) system. Samples of various edible parts of babassu and mandioca flour were homogenized and extracted in goitrogen-free water (GFW) for in vivo experiments, and in methanol (100 g/l), GFW or 0.06 mol/l phosphate buffer (pH 7.0) for in vitro experiments. The edible parts of babassu produced significant in vivo antithyroid effects (p < 0.05- < 0.001) in rats on a high iodine intake (14 micrograms I- day-1.rat-1), as well as distinct and reproducible antithyroid and anti-TPO activities in both in vitro systems, their action being similar to that of the
thionamide-like antithyroid drugs propylthiouracil and methimazole.(ABSTRACT
TRUNCATED AT 250 WORDS)
[The coconut babacu (Orbignya phalerata martins) as a probable risk of human infection by the agent of chromoblastomycosis in the State of Maranhão, Brazil]
Silva CM; da Rocha RM; Moreno JS; Branco MR; Silva RR; Marques SG; Costa JM
Rev Soc Bras Med Trop, 28: 1, 1995 Jan-Mar, 49-52
During a survey of 30 patients with chromoblastomycosis followed at the Hospital dos
Servidores do Estado do Maranhão, the authors observed in 2 (6.6%) patients with lesions on the buttock. This is an uncommon site for the initial lesions of chromoblastomycosis. There is often a history of microtraumatism during the farming job hence the more frequent development of lesions in the lower limbs. Both patients had 10 years disease, with the presence of nodules and vegetant warty lesions in coalescent plaques on the right buttock. Etiologic diagnosis made through histopatologic and culture exams, with Fonsecaea pedrosoi isolated. The epidemiological exposure of the patients, was suggested by the fact that both
worked as babaçu coconut cutters a common activity in Maranhão State. The relation
between this kind of professional activity and the development of infection merits for the investigation.
Clinical References on Boldo (Pneumus boldus)
Tavares DC, et al. Evaluation of the genotoxic potential of the alkaloid boldine in mammalian cell systems in vitro and in vivo. Mutat Res, 1994 May
Abstract Available
Moreno PR, et al. Genotoxicity of the boldine aporphine alkaloid in prokaryotic and eukaryotic organisms.Mutat Res, 1991 Jun
Abstract Available
Ivorra MD., et.al., Selective action of two aporphines at alpha 1-adrenoceptors and potential-operated Ca2+ channels.
Eur J Pharmacol 231: 165-74 (1993)
Abstract Available
Hu J., et.al., The inhibitory effects of boldine, glaucine, and probucol on TPA-induced down regulation of gap junction function. Relationships to intracellular peroxides, protein kinase C translocation, and connexin 43 phosphorylation.Biochem Pharmacol 50: 1635-43 (1995)
Abstract Available
Cassels BK, et.al., Structure-antioxidative activity relationships in benzylisoquinoline alkaloids. Pharmacol Res 31: 103-7 (1995)
Abstract Available
Johnson MA., et.al., Biosynthesis of ascaridole: iodide peroxidase-catalyzed synthesis of a monoterpene endoperoxide in soluble extracts of Chenopodium ambrosioides fruit. Arch Biochem Biophys, 235: 1, 1984 Nov 15, 254-66
Abstract Available
Lanhers MC, et al. Hepatoprotective and anti-inflammatory effects of a traditional medicinal plant of Chile, Peumus boldus. Planta Med, 1991 Apr
Abstract Available
Girón LM, et al. Ethnobotanical survey of the medicinal flora used by the Caribs of Guatemala. J Ethnopharmacol, 1991 Sep
Abstract Available
Speisky H, et al. Boldo and boldine: an emerging case of natural drug development. Pharmacol Res, 1994 Jan-Feb
Abstract Available
Backhouse N, et al. Anti-inflammatory and antipyretic effects of boldine. Agents Actions, 1994 Oct
Abstract Available
Kang JJ, et al. Studies on neuromuscular blockade by boldine in the mouse phrenic nerve-diaphragm. Jpn J Pharmacol. 1998 Feb;76(2):207-12.
Abstract Available
Kang JJ, et al. Effects of boldine on mouse diaphragm and sarcoplasmic reticulum vesicles isolated from
skeletal muscle. Planta Med. 1998 Feb;64(1):18-21.
Abstract Available
Gotteland M, et al [Effect of a dry boldo extract on oro-cecal intestinal transit in healthy volunteers]. Rev Med Chil. 1995 Aug;123(8):955-60.
Abstract Available
Other Clinical References:
Lévy-Appert-Collin MC, et al. [Galenic preparations from Peumus boldus leaves (Monimiacea) J Pharm Belg, 1977 Jan-Feb
Vanhaelen M. [Spectrophotometric microdetermination of alkaloids in Peumus boldus] J Pharm Belg, 1973 May-Jun
Hughes DW, et al. Alkaloids of Peumus boldus. Isolation of laurotetanine and laurolitsine. J Pharm Sci, 1968 Sep
Hughes DW, et al. Alkaloids of Peumus boldus. Isolation of (+) reticuline and isoboldine. J Pharm Sci, 1968 Jun
Krug H, et al. [New flavonol glycosides from the leaves of Peumus boldus Molina] Pharmazie, 1965 Nov, Published in German
Check Medline for new articles.
Studies on neuromuscular blockade by boldine in the
mouse phrenic nerve-diaphragm.
Kang JJ, Cheng YW, Fu WM
Jpn J Pharmacol 1998 Feb;76(2):207-12
The effects of boldine [(S)-2,9-dihydroxyl-1,10-dimethoxy-aporphine], a major alkaloid in the
leaves and bark of Boldo (Peumus boldus Mol.), on neuromuscular transmission were studied using a
muscle phrenic-nerve diaphragm preparation. Boldine at concentrations lower than 200 microM
preferentially inhibited, after an initial period of twitch augmentation, the nerve-evoked twitches of the
mouse diaphragm and left the muscle-evoked twitches unaffected. The twitch inhibition could be
restored by neostigmine or washout with Krebs solution. The twitches evoked indirectly and directly
were both augmented initially, suggesting that the twitch augmentation induced by boldine was
myogenic. Boldine inhibited the acetylcholine-induced contraction of denervated diaphragm
dose-dependently with an IC50 value of 13.5 microM. At 50 microM, boldine specifically inhibited
the amplitude of the miniature end plate potential. In addition, boldine was similar to d-tubocurarine in
its action to reverse the neuromuscular blocking action of alpha-bungarotoxin. These results showed
that the neuromuscular blockade by boldine on isolated mouse phrenic-nerve diaphragm might be
due to its direct interaction with the postsynaptic nicotinic acetylcholine receptor.
Effects of boldine on mouse diaphragm and sarcoplasmic
reticulum vesicles isolated from skeletal muscle.
Kang JJ, Cheng YW
Planta Med 1998 Feb;64(1):18-21
The effects of boldine [(S)-2,9-dihydroxy-1,10-dimethoxyaporphine], a major alkaloid in the leaves
and bark of boldo (Peumus boldus Mol.), on skeletal muscle were studied using mouse diaphragm
and isolated sarcoplasmic reticulum membrane vesicles. Boldine, at 10-200 microM, has little effect
on the muscle-evoked twitches; however, the ryanodine-induced contracture was potentiated
dose-dependently. At higher concentrations of 300 microM, boldine by itself induced muscle
contracture of two phases, which were caused by the influx of extracellular Ca2+ and induction of
Ca2+ release from the internal Ca2+ storage site, the sarcoplasmic reticulum, respectively. When
tested with isolated sarcoplasmic reticulum membrane vesicles, boldine dose-dependently induced
Ca2+ release from actively loaded sarcoplasmic reticulum vesicles isolated from skeletal muscle of
rabbit or rat which was inhibited by ruthenium red, suggesting that the release was through the Ca2+
release channel, also known as the ryanodine receptor. Boldine also dose-dependently increased
apparent [3H]-ryanodine binding with the EC50 value of 50 microM. In conclusion, we have shown
that boldine could sensitize the ryanodine receptor and induce Ca2+ release from the internal Ca2+
storage site of skeletal muscle.
[Effect of a dry boldo extract on oro-cecal intestinal transit in healthy volunteers].
[Article in Spanish]
Gotteland M, Espinoza J, Cassels B, Speisky H
Rev Med Chil 1995 Aug;123(8):955-60
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.
Evaluation of the genotoxic potential of the alkaloid boldine in mammalian cell systems in vitro and in vivo.
Tavares DC; Takahashi CS
Dep. Genetica, Fac. Med. Ribeirao Preto-USP, Brazil.
Mutat Res 321: 139-45 (1994)
Abstract
Boldine is an alkaloid present in Peumus boldus (popularly called "boldo-do-chile" in Brazil) which has healing properties and is used for the treatment of gastrointestinal disorders. The possible clastogenic effect of the drug was tested in vitro on human peripheral blood lymphocytes by evaluating the induction of chromosome aberrations and sister-chromatid exchanges (SCEs). Cultures from different individuals were treated with boldine at concentrations of 10, 20 and 40 micrograms/ml of culture medium.
The effect of the alkaloid was also tested in an in vivo assay using BALB/c mouse bone marrow cells. Boldine was administered to the animals by gavage at the concentrations of 225, 450 and 900 mg/kg body weight. Under the conditions used, boldine did not induce a statistically significant increase in the frequency of chromosome aberrations or SCEs in either test system.
Genotoxicity of the boldine aporphine alkaloid in prokaryotic and eukaryotic organisms.
Moreno PR; Vargas VM; Andrade HH; Henriques AT; Henriques JA
Pos-Graduacao em Farmacia-UFRGS, Porto Alegre, RS, Brazil.
Mutat Res 260: 145-52 (1991)
Abstract
The aporphine alkaloid boldine, present in Peumus boldus (boldo-do-Chile) widely used all over the world, was tested for the presence of genotoxic, mutagenic and recombinogenic activities in microorganisms. This alkaloid did not show genotoxic activity with or without metabolic activation inthe SOS chromotest and Ames tester strains TA100, TA98 and TA102. It was not able to induce point and frameshift mutations in haploid Saccharomyces cerevisiae cells. However, mitotic recombinational events such as crossing-over and gene conversion were weakly induced in diploid yeast cells by this alkaloid. Also, boldine was able to induce weakly cytoplasmic 'petite' mutation in haploid yeast cells.
Selective action of two aporphines at alpha 1-adrenoceptors and potential-operated Ca2+ channels.
Ivorra MD; Chulia S; Lugnier C; D'Ocon MP
Departamento de Farmacologia, Facultad de Farmacia, Universitat de Valencia, Spain.
Eur J Pharmacol 231: 165-74 (1993)
Abstract
Contractions evoked by noradrenaline (1 microM) or a depolarizing solution of 60 mM KCl were concentration dependently depressed by the aporphine alkaloids (S)-boldine and (R)-apomorphine in rat aorta. Both drugs had a greater inhibitory potency on the contraction elicited by noradrenaline. Dose-response curves for noradrenaline were shifted to the right in presence of (S)-boldine. (R)-Apomorphine acted by a complex mechanism at alpha 1-adrenoceptors and its inhibitory effect was irreversible. The conformational features of these alkaloids may explain their different behaviour at alpha 1-adrenoceptors. In Ca(2+)-free solution, the alkaloids inhibited the contraction evoked by noradrenaline but did not modify (apomorphine) or increase (boldine) the contractile response induced by caffeine. Both alkaloids interacted with [3H]prazosin binding and with the benzothiazepine binding site of the Ca2+ entry receptor complex but had no effect at the dihydropyridine binding site in the rat cerebral cortex. Both
drugs showed some selectivity as inhibitors of [3H]prazosin binding as opposed to [3H]d-cis diltiazem binding. (R)-Apomorphine slightly inhibited one of the two forms of the Ca(2+)-independent, low Km cyclic AMP-phosphodiesterase (type IV), whereas it did not have a significant effect on the other phosphodiesterase forms. (S)-Boldine had negligible inhibitory effects on all phosphodiesterase forms. The present study provides evidence that (S)-boldine and (R)-apomorphine have interesting properties as Ca2+ entry blockers (through the benzothiazepine receptor site in the Ca2+ channel) and at alpha 1-adrenoceptors.
The inhibitory effects of boldine, glaucine, and probucol on TPA-induced down regulation of gap junction function. Relationships to intracellular peroxides, protein kinase C translocation, and connexin 43 phosphorylation.
Hu J; Speisky H; Cotgreave IA
Division of Toxicology, Karolinska Institute, Stockholm, Sweden.
Biochem Pharmacol 50: 1635-43 (1995)
Abstract
The naturally occurring antioxidant boldine and its di-methoxy analogue glucine, as well as the drug antioxidant probucol, all inhibit TPA-induced downregulation of gap junctional intercellular communication in WB-F344 rat liver epithelial cells in dose-
dependent manners. The compounds were essentially 100% inhibitory to the effect of TPA (10 nM) at 50 microM each. Analysis of the mechanism of the antitumor promotive action of these agents in vitro revealed that boldine and probucol (both at 10 microM)
totally inhibited the TPA-induced accumulation of intracellular oxidants. Additionally, boldine, glaucine, and probucol, each at 50 microM, inhibited TPA-induced translocation of protein kinase C (PKC) to the particulate fraction of the cells, with concomitant inhibition of TPA-induced hyperphosphorylation of gap junctional connexin 43 (cx43) and TPA-induced internalisation of cx43 protein from the plasma membrane of the cells. None of the compounds inhibited the binding of (3H)-PDBu to TPA-specific binding sites in the cells. The results indicate that antioxidant molecules, irrespective of structure, possess common antitumor promotive potential in this model of gap junctional intercellular communication. The data also indicate that the compounds may interfere with the promotive function of TPA, at least in part, by the destruction of oxidants within the cells. Xanthine oxidase was excluded as a major source of such intracellular oxidants because allopurinol (50 microM) did not significantly affect either the accumulation of oxidants in the cells or the downregulation of gap junctional communication in response to TPA. Taken together, these data also suggest that TPA-induced oxidants play a role in the translocation of PKC to cellular membranes and it is at this level where the antioxidants may interfere in TPA-induced downregulation of gap junctional function.
Structure-antioxidative activity relationships in benzylisoquinoline alkaloids.
Cassels BK; Asencio M; Conget P; Speisky H; Videla LA; Lissi EA
Departamento de Quimica, Facultad de Ciencias, Universidad de Chile, Santiago.
Pharmacol Res 31: 103-7 (1995)
Abstract
The antioxidative properties of the aporphines boldine, glaucine and apomorphine, and of the benzyltetrahydroisoquinolines (+/-)-coclaurine and (+/-)-norarmepavine were compared in the brain homogenate autoxidation model. The IC50 values found lay in the 16-20 microM range for the aporphines and were 131.7 microM, and 79.3 microM for coclaurine and norarmepavine, respectively. These results indicate that the antioxidative capacity (AC) of these compounds is related to the presence of the biphenyl system rather than phenol groups. The non-phenolic glaucine inhibited the 2,2'-azobis-(2-amidinopropane)(AAP)-induced inactivation of lysozyme with an IC50 value of 12 microM, while the corresponding values for the phenolic coclaurine and norarmepavine were 10 and 20 microM, respectively. N-Methylation of glaucine to its quaternary ammonium reduced its protective effect by two-thirds. This result suggests that a benzylic hydrogen neighbouring a nitrogen lone electron pair may be the key to the protective effect of non-phenolic aporphines.
Biosynthesis of ascaridole: iodide peroxidase-catalyzed synthesis of a monoterpene endoperoxide in soluble extracts of Chenopodium ambrosioides fruit.
Johnson MA; Croteau R
Arch Biochem Biophys, 235: 1, 1984 Nov 15, 254-66
Abstract:
Ascaridole, an asymmetric monoterpene endoperoxide with anthelmintic properties, occurs asa major constituent (60-80%) in the volatile oil of American wormseed fruit (Chenopodium ambrosioides: Chenopodiaceae), and as a lesser component in the leaf pocket oil of the boldo tree (Peumus boldus: Monimiaceae). Determination of optical activity and chromatographic resolution of naturally occurring ascaridole, and several synthetic derivatives, showed that both wormseed and boldo produce ascaridole in racemic form. The biosynthesis of ascaridole from the conjugated, symmetrical diene alpha-terpinene (a major component of the oil from wormseed) was shown to be catalyzed by a soluble iodide peroxidase isolated from homogenates of C. ambrosioides fruit and leaves. The enzymatic synthesis of ascaridole was confirmed by capillary gas-liquid chromatography and mass spectrometry of the product, which was also shown to be racemic. Optimal enzymatic activity occurred at pH 4.0 in the presence of 2.5 mM H2O2 and 1 mM NaI. Soluble enzyme extracts were fractionated by gel filtration on both Sephacryl S-300 and Sephadex G-100, and were shown to consist of a
high-molecular-weight peroxidase component (Mr greater than 1,000,000, 30% of total
activity) and two other peroxidase species having apparent molecular weights of 62,000 and 45,000 (major component). Peroxidase activity was susceptible to proteolytic destruction only after periodate treatment, suggesting an association of the enzyme(s) with polysaccharide material. Ascaridole biosynthesis from alpha-terpinene was inhibited by cyanide, catalase, and reducing agents, but not by compounds that trap superoxide or quench singlet oxygen. A peroxide transfer reaction initiated by peroxidase-generated I+ is proposed for the conversion of alpha-terpinene to ascaridole.
Hepatoprotective and anti-inflammatory effects of a traditional medicinal plant of Chile, Peumus boldus.
Lanhers MC; Joyeux M; Soulimani R; Fleurentin J; Sayag M; Mortier F; Younos C; Pelt JM
Planta Med, 57: 2, 1991 Apr, 110-5
Abstract:
Dried hydro-alcoholic extract of Peumus boldus (Monimiaceae) has been evaluated for hepatoprotective, choleretic and anti-inflammatory effects in mice and rats, in order to validate or to invalidate traditional therapeutic indications. This extract exerted a significant hepatoprotection of tert-butyl hydroperoxide-induced hepatotoxicity in isolated rat hepatocytes (in vitro technique) by reducing the lipid peroxidation and the enzymatic leakage of LDH; this in vitro efficacy was reinforced by a significant hepatoprotection on CCl4-induced hepatotoxicity in mice (in vivo technique), the plant extract reducing the enzymatic leakage of ALAT. Boldine, the main alkaloid of P. boldus appears to be implicated in this hepatoprotective activity. Choleretic effects, often mentioned in traditional indications, have not been confirmed in rats. Finally, significant and dose-dependent anti-inflammatory effects were obtained on an acute inflammatory process (carrageenan-induced edema test in rats). Boldine does not appear to be involved in such properties.
Ethnobotanical survey of the medicinal flora used by the Caribs of Guatemala.
Girón LM; Freire V; Alonzo A; Cáceres A
J Ethnopharmacol, 34: 2-3, 1991 Sep, 173-87
Abstract:
An ethnobotanical survey was conducted among the Carib population of Guatemala in 1988-1989. In general terms, the sample surveyed possessed a relatively good standard of living. Results indicated that health services were utilized by the population, and that domestic medicine, mainly plants (96.9%) was used by 15% of the population. One hundred and nineteen plants used for medicinal purposes were collected, of which 102 (85.7%) could be identified; a list of these together with the information provided for each plant is presented. The most frequently reported plants used as medicine are: Acalypha arvensis, Cassia alata, Cymbopogon citratus, Melampodium divaricatum. Momordica charantia, Neurolaena lobata,Ocimum basilicum, Petiveria alliacea and Solanum nigrescens. Most of these plants are found in the region, but some are brought from the Highlands or outside of the country, such as Malva parviflora, Matricaria chamomilla, Peumus boldus, Pimpinella anisum, Rosmarinus officinalis and Tagetes lucida. This survey demonstrated that the Carib population of Guatemala has survived in a transcultural environment of African and native Amerindian beliefs.
Boldo and boldine: an emerging case of natural drug development.
Speisky H; Cassels BK
Pharmacol Res, 29: 1, 1994 Jan-Feb, 1-12
Abstract:
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.
Anti-inflammatory and antipyretic effects of boldine.
Backhouse N; Delporte C; Givernau M; Cassels BK; Valenzuela A; Speisky H
Agents Actions, 42: 3-4, 1994 Oct, 114-7
Abstract:
Boldine, an antioxidant alkaloid isolated from Peumus boldus, exhibits a dose-dependent anti-inflammatory activity in the carrageenan-induced guinea pig paw edema test with an oral ED50 of 34 mg/kg. Boldine also reduces bacterial pyrogen-induced hyperthermia in rabbits to an extent which varied between 51% and 98% at a dose of 60 mg/kg p.o. In vitro studies carried out in rat aortal rings revealed that boldine is an effective inhibitor of prostaglandin biosynthesis, promoting 53% inhibition at 75 microM. The latter in vitro effect may be mechanistically linked to the anti-inflammatory and antipyretic effects of boldine exerted in vivo.
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