Phytochemistry and biological properties of Drimys winteri JR et G. Forster var chilensis (DC) A / Fitoquímica y propiedades biológicas de Drimys winteri JR et G. Forster var chilensis (DC) A

Drimys winteri JR et G. Forster var chilensis (DC) A. is a tree native to central and southern Chile. Also it found in part of Argentina. It is abundant in wet swampy localities from sea level to an altitude of 1700 m. This tree is sacred for the Mapuche culture; it is used in folk medicine in such as inflammatory and painful processes. Phytochemical studies have demonstrated that this plant contains mainly sesquiterpenes of the drimane type, flavonoids, essential oils, phytosterols and some lignans. These drimanes have attracted interest because of their antifeedant, plant growth regulation, cytotoxic, antimicrobial and insecticidal properties. The objective of this review is to establish clearly the phytochemistry and biological activity of Drimys winteri JR et G. Forster var chilensis (DC) A. Articles based on other varieties are not considered.

Drimys winteri JR et G. Forster var chilensis (DC) A. es un árbol nativo del centro y sur de Chile. También se encuentra en parte de Argentina. Es abundante en localidades pantanosas y húmedas desde el nivel del mar hasta una altitud de 1700 m. Este árbol es sagrado para la cultura mapuche. Se utiliza en la medicina popular para tratar enfermedades como procesos inflamatorios y dolorosos. Los estudios fitoquímicos han demostrado que esta planta contiene principalmente sesquiterpenos del tipo drimano, flavonoides, aceites esenciales, fitoesteroles y algunos lignanos. Estos drimanos han despertado interés debido a sus propiedades antialimentarias, regulación del crecimiento de las plantas, propiedades citotóxicas, antimicrobianas e insecticidas. El objetivo de este examen es establecer claramente la fitoquímica y la actividad biológica de Drimys winteri JR et G. Forster var chilensis (DC) A. No se consideran los artículos basados en otras variedades D. winteri var winteri.

Vibrational Circular Dichroism Absolute Configuration of 9,12-Cyclomulin-13-ol, a Diterpene from Azorella and Laretia Species.

The absolute configuration of the diterpenoid 9,12-cyclomulin-13-ol (1), a constituent of Azorella and Laretia species, has been established by vibrational circular dichroism spectroscopy in combination with density functional theory calculations. The obtained normal diterpene absolute configuration confirms that of azorellanol (2), which was determined by single crystal X-ray diffraction.

Antimicrobial Diterpenes from Azorella Species Against Gram-Positive Bacteria.

The present study was aimed at evaluating the antibacterial activity of mulinane and azorellane diterpenes isolated from the Andean plants Azorella compacta and A. trifoliolata and semisynthetic derivatives against reference and multidrug-resistant strains. The results revealed that the semisynthetic compound 7-acetoxy-mulin-9,12-diene (5) exhibited antibacterial activity against reference and multidrug-resistant strains of Staphylococcus aureus and moderate antimycobacterial activity against Mycobacterium smegmatis ATCC 14468.

An unusual mulinane diterpenoid from the Chilean plant Azorella trifurcata (Gaertn) Pers.

Four new mulinane-type diterpenoids besides the known compounds mulin-11,13-dien-20-oic acid, 13α-hydroxyazorellane, 13ß-hydroxyazorellane, mulinolic acid, azorellanol, and mulin-11,13-dien-18-acetoxy-16,20-dioic acid were isolated from the Chilean plant Azorella trifurcata. One of the new metabolites isolated, 7α-acetoxy-9-epi-13ß-hydroxymulinane, possesses a new trans-syn-trans arrangement in a tricyclic ring system not previously encountered in nature. Among the mulinane diterpenoids isolated, mulin-11,13-dien-20-oic acid showed the gastroprotective effect on HCl-EtOH-induced gastric lesions in mice (ED50 = 55 mg kg(-1)). Regarding the mode of gastroprotective action for this active compound, its effect was reduced by pre-treatment of the mice with indomethacin and N-ethylmaleimide, suggesting that prostaglandins and sulfhydryl compounds are positively involved in the gastroprotective activity using this model.

New diterpenes from Azorella spinosa.

Two new diterpenes,2-acetoxy-13-hydroxy-mulin-11-ene and 2-acetoxy-mulin-11, 13-diene,have been isolated from the aerial parts of Azorella spinosa and their structures determined by spectroscopic and conventional chemical methods. Furthermore, 2, 13-dihydroxy-mulin-11-ene was obtained using a basic hydrolysis of the first compound. Two diterpenes reported for other Azorella species have also been found, namely mulinolic acid and 13beta-hydroxyazorellane, as well as the triterpene lactone of ursolic acid,quercetin, and 7-hydroxycoumarin. The compounds were evaluated using antibacterial, antioxidant and enzymatic assays; no significant activity was detected.

Induction of defensive response in Eucalyptus globulus plants and its persistence in vegetative propagation.

The expression of defensive compounds derived from secondary metabolism in plants of Eucalyptus globulus Labill, and the persistence of these in vegetative propagation was evaluated by gas chromatography with flame ionization (GC-FID) and mass spectrometry (MS). The plants were induced by attack from the insect Ctenarytaina eucalypti ("blue gum psyllid") and by mechanical damage. Defense responses were activated in plants for the different types of tested induction. We identified four defensive compounds present in the leaves of plants induced in entomological form (beta-terpineol, aromadendrene, caryophyllene-oxide and eremophilene); all remained in the vegetative propagation. After mechanical induction, we identified three compounds (beta-terpineol, aromadendrene and ledol), of which ledol and aromadendrene persisted in the vegetative propagation. Virtually all the compounds detected, in addition to persisting in the vegetative propagation, showed specificity for the induction type, whether entomological or mechanical, except for aromadendrene, which was expressed in both types of induction.

Determination of antibacterial, antioxidant, antiplatelet and inhibition of cholinesterase activities from the methanolic extracts of Azorella species (Apiaceae) / Determinación de la actividad antibacteriana, antioxidante, antiagregante plaquetaria e inhibición de la colinesterasa a partir de los extractos metanólicos de especies Azorella (Apiaceae)

In this study, we investigated the potential antibacterial, antioxidant and anti-platelet activities and the inhibition of cholinesterase from the methanolic extracts obtained from aerial parts of the two species of Azorella: A. spinosa (Constitution, Chile) and A. monantha (Torres del Paine, Enladrillado and Paso Vergara). All extracts showed only moderate inhibitory activity on acetylcholinesterase (AChE), the most active extract with IC50 = 27ug/mL was A. spinosa. Inhibition of platelet aggregation induced by ADP presented maximal aggregation to 70 and 57 percent on extracts of A. spinosa and A. monantha (Paso Vergara), respectively. The most active extract with antioxidant effect was A. spinosa with IC50 of 28.72ug/mL. Antibacterial activity of the extract on Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii was not present. The extracts of A. spinosa and A. monantha (Paso Vergara) presented the best results on the activities that were evaluated.

En este estudio se investigó las potenciales actividades antibacteriana, antioxidante, antiplaquetaria e inhibición de la colinesterasa de extractos metanólicos a partir de las partes aéreas de dos especies de Azorella: A. spinosa (Constitución, Chile) y A. monantha (Torres del Paine, Enladrillado y Paso Vergara). Todos los extractos mostraron actividad inhibidora moderada solamente sobre acetilcolinesterasa (AChE), siendo el más activo el extracto de A. spinosa con IC50= 27ug/mL. La inhibición de la agregación plaquetaria inducida por ADP presentó máxima agregación al 70 y 57 por ciento sobre los extractos de A. spinosa y A. monantha (Paso Vergara) respectivamente. El extracto más activo con efecto antioxidante fue el de A. spinosa con un IC50 de 28,72ug/mL,). No se presentó actividad antibacteriana de ningún extracto sobre Escherichia coli, Pseudomonas aeuroginosa y Acinetobacter baumannii. Los extractos de A. spinosa y A. monantha (Paso Vergara) presentan los mejores resultados sobre las actividades evaluadas, lo que permite el estudio bioguiado de los metabolitos presentes en estos extractos.

Biological activity of isoflavonoids from Azorella madreporica.

Four isoflavones, isolated from the whole plant of Azorella madreporica, were identified as angustone C (1), alpinumisoflavone (2), licoisoflavone A (3) and isolupalbigenin (4) by spectroscopic studies. The compounds were evaluated for antibacterial and gastroprotective activities. This is the first time that isoflavonoids have been reported in this genus.

Gastroprotective activity of epitaondiol and sargaol.

The effects of epitaondiol (1) and sargaol (2), isolated from the brown alga Stypopodium flabelliforme on HCl/ethanol-induced gastric lesions in mice were evaluated and compared with that of lansoprazole. Epitaondiol and sargaol (6.25 - 50 mg/kg) dose-dependently inhibited the appearance of gastric lesions in mice, displaying similar values to lansoprazole at 20 mg/kg. Both epitaondiol and sargaol showed gastroprotective activity with ED50 values of 40 mg/kg and 35 mg/kg, respectively. The results suggest that epitaondiol and sargaol protect the gastric mucosa in the HCl/EtOH model in mice.

Diterpenoids from Azorella madreporica and their antibacterial activity.

Two new diterpenoids, mulin-12-en-16-al-20-oic acid and 13-α-hydroxy-mulin-11-en-14-one-20-oic acid, were isolated from Azorella madreporica. Their structures were identified on the basis of one-dimensional and two-dimensional NMR experiments. Their antibacterial activity was also tested.

Antituberculosis activity of natural and semisynthetic azorellane and mulinane diterpenoids.

The antituberculosis activity of 14 natural azorellane and mulinane diterpenoids isolated from Azorella compacta, Azorella madreporica, Mulinum crassifolium, and Laretia acaulis, together with eight semisynthetic derivatives, was evaluated against two Mycobacterium tuberculosis strains. The natural azorellanes azorellanol (3) and 17-acetoxy-13-alpha-hydroxyazorellane (6), and the semisynthetic mulinanes 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13) and mulinenic acid methyl ester (23), showed the strongest activity, with MIC values of 12.5 microg/mL against both strains. The methylated derivatives 13-hydroxy-mulin-11-en-20-oic-acid methyl ester (13), mulin-11,13-dien-20-oic acid methyl ester (15) and mulinenic acid methyl ester (23) proved to be more active than the parent compounds.

Microbial transformation of marine halogenated sesquiterpenes.

The sesquiterpene pacifenol is one of the main constituents of the red alga Laurencia claviformis. Earlier work on the semisynthetic derivatives of pacifenol afforded a series of halogenated sesquiterpenes. The aim of the present work was to obtain new hydroxylated derivatives of halogenated sesquiterpenes by means of microbial transformation using Aspergillus niger, Gibberella fujikuroi and Mucor plumbeus. The best results were obtained with M. plumbeus. The microbiological transformation by M. plumbeus of pacifenol, and two semisynthetic derivatives, is described. The structures of the new compounds obtained were determined by spectroscopic means.

VCD determination of the absolute configuration of stypotriol.

The absolute configuration of the pentacyclic ichthyotoxin stypotriol, a constituent of Stypopodium zonale, was deduced to be 3S,5R,8R,9R,10S,13S,14S-(-)-1 by vibrational circular dichroism spectroscopy of the derived triacetate 2 in comparison to DFT B3LYP/DGDZVP calculations. Compound 2, C33H46O7 having 300 electrons, is the largest natural product successfully studied by VCD to date.

Azorellane diterpenoids from Laretia acaulis inhibit nuclear factor-kappa B activity.

Transcription factor NF-kappaB plays a key role in the inducible expression of genes mediating proinflammatory effects, and is thus an important target for the development of antiinflammatory drugs. Laretia acaulis (Cav.) Gill et Hook (Apiaceae) is a medicinal plant used in the high Andes mountains for different ailments such as diabetes, inflammation and for general pain. In addition to the known azorellanol (2) and 7-deacetylazorellanol (4), 13-epiazorellanol (1) was also isolated from the aerial part of this plant. Its structure was based on spectroscopic comparison with azorellanol (2) and by chemical characterization. While compounds 2 and 4 showed potent anti-NF-kappaB activity by targeting the activity of the IkappaBalpha kinase, compound 1 was completely inactive highlighting the importance of position 13 in the biological activities of this class of tetracyclic diterpenoids.

Experimental antihyperglycemic effect of diterpenoids of llareta Azorella compacta (Umbelliferae) Phil in rats.

Aqueous or ethanol infusions of Azorella compacta (llareta) in common with many other plants have been used as antidiabetic in the popular medicine in the altiplanic region of Chile. In order to determine if the diterpenic compounds chemically elucidated and isolated from this plant are responsible for this effect, streptozotocin diabetic rats (507 +/- 67 mg/mL glucose) were injected with two injections of diterpenic compounds mulinolic acid, azorellanol, and mulin-11,13-dien-20-oic acid at 180 mg/mL. Glycemia of animals treated with mulinolic acid and azorellanol was decreased to 243 +/- 2 and 247 +/- 14 mg/mL respectively, values very close to those reached by chlorpropamide injection used in controls. After 3 h treatment with mulin-11,13-dien-20-oic acid no effect was detected. The blood serum insulin in diabetic rats (146 +/- 58 pg/mL) was lower than in control rats. After injection of azorellanol, insulin was elevated to 247 +/- 23 pg/mL but with mulinolic acid, insulin was not changed. The antihyperglycemic effect of these compounds may explain the effectiveness of llareta in popular medicine. Because of the similarity to the hypoglycemic medication chlorpropamide, azorellanol could be acting on the beta cells of pancreatic islets, while mulinolic acid may act upon glucose utilization or production in the liver.

Pharmaco-toxicological study of diterpenoids.

Azorella compacta, Azorella yareta and Laretia acaulis (Apiaceae) are native species from the high Andes Mountains, northeastern Chile, and they have being traditionally used to treat asthma, colds and bronchitis, illnesses with inflammation and pain as the main symptoms. Interestingly, there are no scientific reports available on their benefits or toxicity. This study was carried out with the purpose of validating the medicinal use of these species and to discover anti-inflammatory and analgesic new molecules. As a working hypothesis, we have proposed that these medicinal species contain bioactive compounds with anti-inflammatory and analgesic effects. In this context, azorellanol, 13-hydroxy-7-oxoazorellane and 7-deacetylazorellanol, three diterpenoids previously isolated only from these plants, were subjected to farmaco-toxicological evaluation. Their topical anti-inflammatory and analgesic activities along with acute toxicities or innocuosness were also investigated. Our results indicate the absence of toxic and side effects in mice. All compounds presented dose-related inhibition of pain. 13-hydroxy-7-oxoazorellane was the most potent analgesic but it was less effective than sodium naproxen, the reference drug. Azorellanol exhibited the highest topical anti-inflammatory potency on AA (arachidonic acid) and TPA (12-deoxyphorbol 13-tetradecanoate) induced oedema, and it effect was similar to the reference drugs (nimesulide and indomethacin). Probably, its mechanism of action could be explained through the inhibition to cyclo-oxygenase activity. Our results corroborate the anti-inflammatory and analgesic effects of these species, and it justifies their use in folk medicine.

Yaretol, a norditerpenoid from Azorella madreporica.

A new norditerpenoid, yaretol (1), was isolated from the whole plant of Azorella madreporica. The structure of 1 was established by one- and two-dimensional NMR techniques and confirmed by X-ray diffraction analysis.