Plant Profiler

Boldo (Peumus boldus)


Boldo (Peumus boldus) Image
Synonyms / Common Names / Related Terms
1,8-cineol, 2-decanone, 2-heptaone, 2-octanone, 2-tridecanone, 2-undecanone, 6(a)-7 dehydroboldine, ascaridole, asymmetric monoterpene endoperoxide, baldina, boldine ([s]-2,9-dihydroxy-1, 10-dimethoxyaporphine), Boldea fragrans, boldina, boldine, boldine houde, boldoa, Boldoa fragrans, boldoak boldea, boldo-do-Chile, boldo folium, boldoglucin, boldu, Boldu boldus, boldus, boldus boldus, bolldin, bornyl-acetate, Chilean boldo tree, coclaurine, coumarin, cuminaldehyde, diethylphthalate, eugenol, farnesol, fenchone, gamma terpinene, isoboldine, kaempferols, laurolitsine, laurotetainine, Monimiaceae (family), molina, norboldine, norisocorydine, pachycarpine, P-cymene, P-cymol, Peumus boldus, Peumus boldus Mol., Peumus fragrans, pro-nuciferine, qian-hu, reticuline, rhamnosides, sabinene, sinoacutine, tannins, terpinoline, thymol, trans verbenol.

Combination products (examples): Sympathyl® (phenobarbitone, methenamine, boldo, and crataegus extracts).

Mechanism of Action

Pharmacology:

  • Constituents: Boldine is a major active alkaloidal constituent of boldo. In addition to boldine, boldo contains ascaridole, benzaldehyde, boldin, boldoglucin, bornyl-acetate, 1,8-cineol, coclaurine, coumarin, cuminaldehyde, 2-decanone, 6(a)-7 dehydroboldine, diethylphthalate, eugenol, farnesol, fenchone, gamma terpinene, 2-heptaone, isoboldine, kaempferols, laurolitsine, laurotetainine, norboldine, norisocorydine, pachycarpine, P-cymene, P-cymol, pro-nuciferine, 2-octanone, reticuline, rhamnosides, sabinene, sinoacutine, terpinoline, thymol, trans verbenol, 2-tridecanone, and 2-undecanone.
  • Antioxidant effects: Preliminary assays showed free-radical scavenging activity in hot water extracts of boldo leaves.5 Assay-guided isolation led to the active compounds. Catechin proved to be the main free-radical scavenger of the extracts. Lipid peroxidation in erythrocytes was inhibited by boldo extracts. The relative concentration of alkaloids and phenolics in boldo leaves and their activity suggest that the free-radical scavenging effect is mainly due to catechin and flavonoids and that the antioxidant effect is mainly related with the catechin content. The high catechin content of boldo leaves and its bioactivity suggest that quality control of boldo folium has to combine the analysis of catechin as well as their characteristic aporphine alkaloids.
  • The influence of Peumus boldus on the labeling of red blood cells and plasma proteins with 99mTc was studied.8 Aliquots of plasma and blood cells were isolated from the mixture and treated with trichloroacetic acid (TCA). Boldo increased technetium-99m uptake by red blood cells by 90% at all concentrations, an effect that persisted in the presence of increased concentrations of stannous chloride. The authors note that these results indicate that the antioxidant action of boldo protects the stannous ion, contributing to increased reduction of the pertechnetate ion and increasing the percentage of radioactivity bound to the red blood cell in vitro.
  • Boldine reduced the lethal effect induced by stannous chloride on the survival of Escherichia coli in vitro.9 Stannous chloride strongly inactivated E. coli cells, but the toxic effect was eradicated by boldine. Boldine also prevented the modification of the supercoiled form of E. coli deoxynucleic acid plasmid caused by stannous chloride. The authors suggest that boldine may protect the stannous chloride ion from oxidation, thus avoiding the generation of reactive oxygen species.
  • Boldine dose-dependently inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced down-regulation of gap junctional intercellular communication in rat liver epithelial cells in vitro, and totally inhibited the TPA-induced accumulation of intracellular antioxidants.10 Boldine dose-dependently reversed the TPA-induced inhibition of gap junctional intercellular communication (GJIC), with nearly complete reinstatement of cellular communication at 50µM concentration of boldine. Co-incubation of boldine with TPA also caused a dose-dependent decrease in the accumulation of oxidants in the cell (p<0.001). The authors report that antioxidants, like boldine, may exercise antitumor effects through the destruction of free radicals generated in the tumor-promotion process.
  • Boldine, in low micromolar concentrations, was able to prevent brain homogenate autooxidation, the 2,2'-azobis(2-amidinopropane)(AAP)-induced lipid peroxidation of red cell plasma membranes, and the AAP-induced inactivation of lysozyme.11 These results are indicative of a high reactivity of boldine towards free radicals. The authors suggest that boldine's antioxidant activity in vitro appears lower than synthetic antioxidants such as propyl gallate but, because of its low toxicity, may be a useful therapeutic agent.
  • Boldine decomposed superoxide anions, hydrogen peroxides and hydroxyl radicals in a dose-dependent manner.1 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 streptozotocin (STZ)-induced oxidative tissue damage and may alter 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.
  • Peumus boldus showed high Trolox-Equivalent Antioxidant Capacity (TEAC) and HCIO-quenching activities.4
  • Antiplatelet effects: Boldine inhibited aggregation of rabbit platelets and inhibited the release of ATP-induced by arachidonic acid and collagen in rabbit platelets.12
  • Chemoprotective effects: In vitro modulations of drug-metabolizing enzymes in mouse hepatoma Hepa-1 cell line and mouse hepatic microsomes were investigated.3 Boldine manifested inhibition activity on hepatic microsomal cytochrome P4501A-dependent 7-ethoxyresorufin O-deethylase and cytochrome P4503A-dependent testosterone 6 beta-hydroxylase activities and stimulated glutathione S-transferase activity in Hepa-1 cells. The authors concluded boldine may decrease the metabolic activation of other xenobiotics including chemical mutagens.
  • Gastrointestinal effects: Gotteland et al. conducted a study to assess the effects of a dry boldo extract on orocecal transit time in normal humans.13 Twelve volunteers received 2.5g of a dry boldo extract or a placebo (glucose) during two successive periods of four days. On the fourth day, 20g of lactulose were administered and breath hydrogen was collected every 15 minutes. Orocecal transit time was defined as the time in which breath hydrogen increased by 20ppm over the fasting level. Orocecal transit time was larger after dry boldo extract administration, compared to placebo (112.5 ± 15.4 and 87 ± 11.8 minutes respectively, p<0.05). It was concluded that dry boldo extract prolongs oro cecal transit time and gives a possible explanation for its medicinal use.
  • Hepatoprotective effects: Boldine acted as a hydroxide scavenger, inhibited NADPH- and NADH-dependent production of thiobarbituric acid reactive substances (TBARS), inhibited ferrous-catalyzed non-enzymatic lipid peroxidation, and inhibited lipid peroxidation initiated by t-butylhydroperoxide and carbon tetrachloride.2 Boldine protected microsomes against oxidation of NADPH-cytochrome P450 reductase, cytochrome P450, and glucose-6-phosphatase.
  • Boldine produced nearly complete inhibition of NADPH- and NADH-dependent peroxidation, and protected against the loss of cytochrome P450 2E1 produced by incubation of microsomes with NADPH plus ferric-adenosine triphosphate.6
  • Myogenic effects: Boldine was reported to act as a specific calcium entry blocker and did not interfere with contractile machinery in rat uteri in vitro.14
  • Vasodilatory effects: Boldine was found to be an alpha 1-adrenoceptor blocking agent in guinea-pig aorta as revealed by its competitive antagonism of noradrenaline-induced vasoconstriction with comparable efficacy to prazosin.15

Pharmacodynamics/Kinetics:

  • In an animal study, boldine inhibited the acetylcholine-induced contraction of denervated diaphragm dose-dependently with an IC50 value of 13.5µM.7 At 50µM, 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. The 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.
  • Boldine at higher concentrations of 300µM can induce muscle contraction through 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.16 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 50µM. The authors concluded that boldine could sensitize the ryanodine receptor and induce Ca2+ release from the internal Ca2+ storage site of skeletal muscle.

References

  1. Jang, Y. Y., Song, J. H., Shin, Y. K., Han, E. S., and Lee, C. S. Protective effect of boldine on oxidative mitochondrial damage in streptozotocin-induced diabetic rats. Pharmacol Res  2000;42(4):361-371. 10987997
  2. Cederbaum, A. I., Kukielka, E., and Speisky, H. Inhibition of rat liver microsomal lipid peroxidation by boldine. Biochem Pharmacol  11-3-1992;44(9):1765-1772. 1333206
  3. Kubinova, R., Machala, M., Minksova, K., Neca, J., and Suchy, V. Chemoprotective activity of boldine: modulation of drug-metabolizing enzymes. Pharmazie 2001;56(3):242-243. 11265593
  4. Speisky, H., Rocco, C., Carrasco, C., Lissi, E. A., and Lopez-Alarcon, C. Antioxidant screening of medicinal herbal teas. Phytother Res 2006;20(6):462-467. 16619353
  5. Schmeda-Hirschmann, G., Rodriguez, J. A., Theoduloz, C., Astudillo, S. L., Feresin, G. E., and Tapia, A. Free-radical scavengers and antioxidants from Peumus boldus Mol. ("Boldo"). Free Radic Res 2003;37(4):447-452. 12747739
  6. Kringstein, P. and Cederbaum, A. I. Boldine prevents human liver microsomal lipid peroxidation and inactivation of cytochrome P4502E1. Free Radic Biol Med 1995;18(3):559-563. 9101247
  7. Kang, J. J., Cheng, Y. W., and Fu, W. M. Studies on neuromuscular blockade by boldine in the mouse phrenic nerve-diaphragm. Jpn J Pharmacol  1998;76(2):207-212. 9541284
  8. Reiniger, I. W., de Oliveira, J. F., Caldeira-de-Araujo, A., and Bernardo-Filho, M. Effect of Peumus boldus on the labeling of red blood cells and plasma proteins with technetium-99m. Appl Radiat Isot  1999;51(2):145-149. 10376326
  9. Reiniger, I. W., Ribeiro, da Silva, Felzenszwalb, I., de Mattos, J. C., de Oliveira, J. F., Silva Dantas, F. J., Bezerra, R. J., Caldeira-de-Araujo, A., and Bernardo-Filho, M. Boldine action against the stannous chloride effect. J Ethnopharmacol 12-15-1999;68(1-3):345-348. 10624900
  10. Hu, J., Speisky, H., and Cotgreave, I. A. 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 11-9-1995;50(10):1635-1643. 2043147
  11. Speisky, H., Cassels, B. K., Lissi, E. A., and Videla, L. A. Antioxidant properties of the alkaloid boldine in systems undergoing lipid peroxidation and enzyme inactivation. Biochem Pharmacol 6-1-1991;41(11):1575-1581. 2043147
  12. Teng, C. M., Hsueh, C. M., Chang, Y. L., Ko, F. N., Lee, S. S., and Liu, K. C. Antiplatelet effects of some aporphine and phenanthrene alkaloids in rabbits and man. J Pharm Pharmacol 1997;49(7):706-711. 9255715
  13. Gotteland, M., Espinoza, J., Cassels, B., and Speisky, H. [Effect of a dry boldo extract on oro-cecal intestinal transit in healthy volunteers]. Rev Med Chil  1995;123(8):955-960. 8657963
  14. Ivorra, M. D., Martinez, F., Serrano, A., and D'Ocon, P. Different mechanism of relaxation induced by aporphine alkaloids in rat uterus. J Pharm Pharmacol 1993;45(5):439-443. 8099963
  15. Chulia, S., Moreau, J., Naline, E., Noguera, M. A., Ivorra, M. D., D'Ocon, M. P., and Advenier, C. The effect of S-(+)-boldine on the alpha 1-adrenoceptor of the guinea-pig aorta. Br J Pharmacol 1996;119(7):1305-1312. 8968536
  16. Kang, J. J. and Cheng, Y. W. Effects of boldine on mouse diaphragm and sarcoplasmic reticulum vesicles isolated from skeletal muscle. Planta Med 1998;64(1):18-21. 9491763




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