ÚLTIMOS AVANCES EN LA QUÍMICA Y ACTIVIDADES BACTERIOLÓGICAS EN LAS PLANTAS MEDICINALES= Medicinal plants, last advances on chemistry and bacteria activities on the medicinal herbs

1) An aq. ext. of Buddleja globosa leaves, used traditionally in Chile for wound healing, was tested for the ability to stimulate growth of fibroblasts in vitro and for antioxidant activity in the same fibroblast cell system challenged with hydrogen peroxide.  Low concns. of the ext. gave an increase in fibroblast growth which was not statistically significant but cytotoxicity was obsd. at concns. greater than 50 mg/mL.  The ext. showed strong antioxidant effect and fractionation led to the isolation of 3 flavonoids and 2 caffeic acid derivs., each of which was shown to contribute to the antioxidant effect at concns. below 10 mg/mL.  These activities would accelerate the healing of wounds.

2) Lipophilic exts. of the stembark of Buddleja globosa were found to have antifungal activity at 125 mg/mL against three dermatophytic fungal species but had no activity at 1000 mg/mL against four other fungal species or two yeast species.  Bioassay-guided fractionation of Si gel column eluates using the sensitive fungal species resulted in active fractions from which were isolated five compds. that were characterized by spectroscopic methods as one novel and four known compds.  The known compds. were the diterpene buddlejone, the bisditerpene maytenone, and the two sesquiterpenes buddledin A and buddledin B, while the novel compd. was characterized as the diterpene deoxybuddlejone (I).  The min. inhibitory concn. of all the compds. was detd. against all the microorganisms under test, and buddledins A and B were shown to exhibit the greatest antifungal activity, with values of 43 mM and 51 mM, resp., against the sensitive fungi Trichophyton rubrum, Tricophyton interdigitale, and Epidermophyton floccosum. 

3) Angoroside A (I), [3,4-dihydroxy-beta-phenylethoxy-O-alpha-L-arabinopyranosyl-(1®6)-alpa-L-rhamnopyranosyl-(1®3)4-O-caffeoyl-beta-D-glucopyranoside], a compd. exhibiting antibacterial activity against Staphylococcus aureus, has been isolated from an ethanolic ext. of Buddleja globosa leaves.  This is the first report of I in the genus Buddleja and allowed the authors to correlate the activity of the substance with the therapeutic properties described for B. globosa.

4) Previous phytochem. research on this plant has resulted in the isolation and structure detn. of aucubin from the leaves; luteolin and 6-hydroxyluteolin from the leaves acacetin-7-O-rutinoside, apigenin-7-O-glucoside, quercetin-3-O-rutinoside from the flowers; beta-amyrin acetate, beta-amyrin, glutinol, chondrillasterol, and esters of ferulic acids from the leaves and phenolic acid esters from the stembark.  A sample of bioactive fractions (1 g, 1/3 of total residue) was chromatographed over Silica gel (80 g) with a chloroform/methanol (6:1) mixt. as eluent.  The collected fractions were monitored by TLC.  Those fractions showing analogous single spots on concn. yielded 130 mg of pale yellow residue.  Further purifn. by HPTLC [Silica gel, chloroform/methanol

5) ETHNOPHARMACOLOGICAL RELEVANCE: Leaf extracts of Buddleja globosa (Buddlejaceae) are used in Chilean folk medicine for wound healing.  The anti-inflammatory (topic and per os), analgesic (per os) effects and the antioxidant activity of Buddleja globosa were for the first time reported by us.  AIM OF THE STUDY: Assess the antinociceptive activity of the methanol sequential and global extracts using complementary chemical and thermal models of pain, characterize pharmacologically the antinociception induced, evaluate seasonal influence to support Buddleja globosa medicinal use.  MATERIALS AND METHODS: Global methanol, sequential methanol and ethanol (leaves collected in autumn and summer) extracts were evaluated for oral and topic analgesia in tail flick, formalin and writhing models, verbascoside and 7-O-luteolin glucoside were assayed in tail flick and writhing.  Ibuprofen was used as reference.  For characterization of induced antinociception, naltrexone, naltrindole, tropisetron, nor-binaltorphimine, prazosin, yohimbine, atropine, and N-nitro-l-arginine methyl ester were used as antagonists and inhibitors drugs.  RESULTS: Seasonal influence was observed since autumn extract resulted less active.  Extracts showed a dose-dependent antinociceptive activity in all assays, the highest effects were obtained for the formalin and writhing test.  Verbascoside was more active than ibuprofen in the writhing test (67.6% and 50.0% at equimolar doses) and showed similar effects in the tail flick (topic and oral) near 25% at equivalent doses - ED25 or EC25 - to ibuprofen.  Luteolin 7-O-glucoside was slightly more active in the tail flick test and nearly half active than verbascoside in the writhing assay.  Effectiveness was higher for the sequential than for global alcoholic extracts, and can be increased by selective blocking of opioid receptors.  Global methanol extract seems modulated only by naltrexone.  CONCLUSIONS: Analgesic effect of Buddleja globosa is here demonstrated validating its use in traditional medicine.
 Season influence is important to be considered.

6) ETHNOPHARMACOLOGICAL RELEVANCE: Buddleja globosa, known as "matico", is employed in Chile for wound healing.  AIM OF THE STUDY: To validate the traditional use of the crude drug through in vivo and in vitro evaluation of the anti-inflammatory, analgesic and antioxidant properties of its extracts.  MATERIALS AND METHODS: Sequential hexane, dichloromethane, methanol and total methanol extracts were studied using bioguided fractionation.  The following activities were investigated: analgesic (writhing test), oral and topic anti-inflammatory (paw- and ear-induced edema), free radical scavenging and antioxidant activities (1,1-diphenyl-2-picrylhydrazyl, DPPH, superoxide anion, lipid peroxidation and xanthine oxidase inhibition).  Sodium naproxen, nimesulide, indomethacin were used as reference drugs for in vivo, quercetin and allopurinol for in vitro assays.  RESULTS: A mixture of alpha- and beta-amyrins was isolated from the hexane extract that showed 41.2% of analgesic effect at 600 mg/kg, inhibited by 47.7 and 79.0% the arachidonic acid (AA) and 12-deoxyphorbol-13-decanoate (TPA)-induced inflammation at 3mg/20 microL/ear, respectively.  A mixture of beta-sitosterol, stigmasterol, stigmastenol, stigmastanol and campesterol was isolated from the fraction CD4-N and beta-sitosterol-glycoside from the fraction CD5-N, reducing TPA-induced inflammation by 78.2 and 83.7% at 1mg/20 microL/ear, respectively.  The fraction CD4-N at 300 mg/kg also showed analgesic activity (38.7%).  The methanol extract at 600mg/kg per os showed anti-inflammatory effect (61.4%), topic anti-inflammatory (56.7% on TPA) and analgesic activity (38.5%).  Verbascoside and luteolin-7-O-glucoside were the major components of the methanol extract; apigenin 7-O-glucoside was also detected.  Inhibition of superoxide anion, lipoperoxidation, and DPPH bleaching effect was found in the methanol serial and global extracts.
 CONCLUSIONS: The present report demonstrate the analgesic and anti-inflammatory properties of Buddleja globosa and validate its use in Chilean traditional medicine.

7) Lipophilic extracts of the stembark of Buddleja globosa were found to have antifungal activity at 125 microg/mL against three dermatophytic fungal species but had no activity at 1000 microg/mL against four other fungal species or two yeast species.  Bioassay-guided fractionation of Si gel column eluates using the sensitive fungal species resulted in active fractions from which were isolated five compounds that were characterized by spectroscopic methods as one novel and four known compounds.  The known compounds were the diterpene buddlejone (1), the bisditerpene maytenone, and the two sesquiterpenes buddledin A and buddledin B, while the novel compound was characterized as the diterpene deoxybuddlejone (2).  The minimum inhibitory concentration of all the compounds was determined against all the microorganisms under test, and buddledins A and B were shown to exhibit the greatest antifungal activity, with values of 43 microM and 51 microM, respectively, against the sensitive fungi Trichophyton rubrum, Tricophyton interdigitale, and Epidermophyton floccosum.

Summary
Orangel ball tree (Buddleja globosa – Buddlejaceae) is a medicinal plant native to the Andean region of Peru, Chile, Bolivia and Argentina. Most ethnomedical references point out the importance of B. globosa as a wound healing agent and in the treatment of skin ulcers. Matico leaves display a high content of polyphenols, compounds with recognized antioxidant capacity, which may contribute to its therapeutic properties. Accordingly, pharmacological studies have successfully focused on validating these activities and on identifying the active principles present in the plant. It is interesting to point out that in vivo studies have also confirmed the wound healing activity of B. globosa in a gastric model of experimental ulcerogenesis, a fact that could justify further clinical studies in the future.

PARTE UTILIZADA= Used part: Hojas.

ACCIÓN FARMACOLÓGICA= Pharmacological action: Vulnerario (hojas), antidisentérico.

COMPOSICIÓN QUÍMICA= Chemical composition: Buddleja globosa Lam. (common name "Matico") grows in the Central and South regions of Chile. The aqueous extract has been used in the treatment of stomach ulcers and also to cure wounds and brns. Previous works on this plant, show thw presence of aucubin anf the flavonoids luteolin and 6-hydroxy luteolin from hydrolized methanolic extracts. On the other hand in this laboratory the following compounds were isolated from the flowers: acacetin-7-0-rutinoside (I), apigenin-7-0-glucoside (II), quercetin-3-0-rutinoside (III) and scutellarein-7-0-glucoside (IIV). In pursuance on the studies of the constituents of this species, the petroleum and ethyl acetate extract were analized in the present work. We describe the isolation and identification of the triterpenoids beta-amyrin (V), beta-amyrin acetate (VI). Glitinol (VII), the steroid chondrillasterol (VIII), the genins rho-coumaric and methyl ester (IX) and ferulic and methyl ester (X).

ZONA GEOGRAFICA= Geografical zone: Perú, Chile, Bolivia y Argentina. 

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Partes usadas:
hojas

Usos tradicionales:
a) uso interno: úlceras digestivas, indigestión, dolor de estómago, disfunción hepática.
La infusión se prepara con 1 cucharada de hojas para 1 litro de agua recién hervida: beber 1 taza 3 veces al día.
b) uso externo: traumatismos y heridas de la piel.
La misma infusión sirve para lavar heridas y en compresas para contusiones y hematomas (moretones).

Efectos: analgésico, antimicótico, cicatrizante, anti-inflamatorio.

1) TOURSARKISSIAN, Martín. Plantas medicinales de Argentina : sus nombres botánicos, vulgares, usos y distribución geográfica. Buenos Aires : Hemisferio Sur, 1980, p.78.

2) LOPEZ, J., et al Chemical constituents of Buddleja globosa Lam. Fitoterapia. 1979, vol.50, nº5, p.195-198.
 
3) MENSAH, A. Y., et al.  Effects of Buddleja globosa leaf and its constituents relevant to wound healing.   Journal of Ethnopharmacology. 2001, vol.77, nº2-3, p.219-226.
 
4) MENSAH, Abraham Y., et al. Known and novel terpenes from Buddleja globosa displaying selective antifungal activity against dermatophytes.  Journal of Natural Products. 2000, vol.63, nº9, p.1210-1213.
 
5) PARDO, Fernando; PERICH, Fernando; TORRES, Rene. Novel glycoside from Buddleja globosa with bactericidal activity. Boletin de la Sociedad Chilena de Quimica. 1997, vol.42, nº1, p.101-104.
 
6) PARDO, F., et al. Isolation of verbascoside, an antimicrobial constituent of Buddleja globosa leaves.  Journal of Ethnopharmacology. 1993, vol.39, nº3, p.221-222.
 
7) BACKHOUSE, Nadine, et al. Antinociceptive activity of Buddleja globosa (matico) in several models of pain.  Journal of ethnopharmacology. 2008, vol.119, nº1, p.160-165.
 
8) BACKHOUSE, N., et al. Analgesic, anti-inflammatory and antioxidant properties of Buddleja globosa, Buddlejaceae. Journal of ethnopharmacology. 2008, vol.116, nº2, p.263-269.
 
9) MENSAH, A Y., et al. Known and novel terpenes from Buddleja globosa displaying selective antifungal activity against dermatophytes. Journal of natural products. 2000, vol.63, nº9, p.1210-1213.

10) ALONSO, Jorge ; DESMARCHELIER, Cristian. Plantas medicinales autóctonas de la Argentina : bases científicas para su aplicación en atención primaria de la salud.  Buenos Aires: L.O.L.A, 2005, p. 394.

11) Plantas medicinales autóctonas de la Argentina. Bases científicas para su aplicación en atención primaria de la salud / Jorge Alonso y Cristian Jorge Desmarchelier. - 1a ed. - Ciudad Autónoma de Buenos Aires: Corpus Libros Médicos y Científicos, 2015.

12) Hierbas medicinales/ Chile. Ministerio de Agricultura.  p.64