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.
 

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.
 

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.
 

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
 

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.
 

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.
 

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.
 

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.
 

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.