Five centuries of Cirsium ehrenbergii Sch. Bip. (Asteraceae) in Mexico, from Huitzquilitl to Cardo Santo: History, ethnomedicine, pharmacology and chemistry.

ETHNOPHARMACOLOGICAL RELEVANCE: Several medicinal plants, including the endemic herb Cirsum ehrenbergii (Asteraceae), have been documented in manuscripts, medical and botanical books written in Mexico since the XVI century until the present. This unique circumstance is a real window in the time that allows to investigate historical and contemporary ethnopharmacological knowledge. AIM OF THE STUDY: To examine the persistence, disappearance, and transformation of ethnomedicinal knowledge of C. ehrenbergii along time. Also, to investigate the chemistry and pharmacology of this species in relation to its historical and present day main ethnomedical applications related to Central Nervous System and inflammation. MATERIALS AND METHODS: A thorough review was performed of written sources of medicinal plants from XVI and onwards. For the pharmacological studies, the organic extracts were tested in mice models to assess its antidepressant and anti-inflammatory properties. The active extracts were studied chemically. The isolated compounds were identified by 1H, 13C NMR, or characterized by GC-MS. RESULTS: Cirsum ehrenbergii was illustrated for the first time (1552) in the Libellus de Medicinalibus Indorum Herbis (Booklet of Medicinal Plants of the Indians) and named in the Nahuatl native language as huitzquilitl (edible thistle). It was there recommended as nigris sanguinis remedium (remedy for black blood), and for the treatment of illnesses with an inflammatory component. Nigris sanguinis was well known in the European medicine of that time and currently it has been interpreted as "depression". At the present time, peasants and native population in Mexico mainly name C. ehrenbergii in Spanish as cardo Santo (holy thistle). Its original Nahuatl name has been almost forgotten. However, these communities use this species, among other maladies, to heal "nervios" (anxiety and/or depression) and for anti-inflammatory purposes. These ailments and treatments resemble those recorded in the Libellus and in several medicinal plant books along centuries. The ethanol extract of C. ehrenbergii roots showed antidepressant-like activity in mice administered at 300 mg/kg, as indicated by the forced swim test (FST). The glycosylated flavonoid linarin was identified as antidepressant principle and was active at the doses of 30 and 60 mg/kg in the FST. Regarding to anti-inflammatory activity, the most active was the methylene chloride extract of the aerial parts, which contains taraxasterol, pseudotaraxasterol, ß-sitosterol and stigmasterol. CONCLUSIONS: Cirsium ehrenbergii extracts possess antidepressant-like (roots, EtOH) and anti-inflammatory (aerial parts, CH2Cl2) properties, containing active compounds. Our results sustain historical and present day ethnomedical applications of this species documented along five centuries.

Recognition of antioxidants and photosensitizers in Dyssodia pinnata by EPR spectroscopy.

INTRODUCTION: Previous studies report the isolation mainly of terthiophene derivatives and flavonoids from Dyssodia species. Terthiophenes are known as photosensitizers by their capacity to generate singlet oxygen (1 O2 ), and flavonoid antioxidant activity is recognized. These opposite properties could represent interesting options in photodynamic therapy. OBJECTIVE: To determine the antioxidant and photosensitizer activities of extracts and isolates of Dyssodia pinnata by electron paramagnetic resonance (EPR). METHODOLOGY: Extracts and isolates were evaluated as antioxidants by the interactions with copper ion (Cu2+ ) observed in EPR, and by the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) and the thiobarbituric reactive substances (TBARS) methods. Their abilities as 1 O2 producers were also estimated by EPR. RESULTS: Terthiophenes were obtained from hexane (DPH) and acetone (DPA) extracts, and flavonoids from DPA and methanol (DPM) extracts. The interaction with Cu2+ of extracts and isolated compounds of Dyssodia pinnata showed two effects in EPR: reduction and chelation; flavonoids exhibited both effects, while terthiophenes showed only reduction. DPA, DPM, and flavonoids were active in DPPH and TBARS assays. Quercetagetin-7-O-ß-glucoside showed the highest antioxidant and chelating activities, 3-glycosidated flavonoids were less active. Upon irradiation extracts and terthiophenes induced 1 O2 formation. CONCLUSION: Flavonoid reducing activity on Cu2+ and free radical scavenging capacity were related to the number of hydroxy groups and to the conjugation between the B and C rings. All tested flavonols showed a major complex with Cu2+ , with the most probable site of chelation between the 5-hydroxy and 4-oxo groups. Extracts and terthiophene derivatives showed photosensitizer activity. Thus, EPR is useful to evaluate free radical scavenging and pro-oxidant properties.

Chemical Composition and Antimicrobial Activity of Ageratina deltoidea.

The chemical study of Ageratina deltoidea afforded grandiflorenic acid (1), ent-kaurenoic acid (2), and eight benzylbenzoates (3 - 10), two of them, 3,5-dimethoxybenzyl 2,3,6-trimethoxybenzoate (5) and 4-(ß-d-glucopyranosyloxy)-3-hydroxybenzyl 2,6-dimethoxybenzoate (9), described for the first time. In addition, the new sesquiterpene lactone deltoidin C (13), together with the known 11 and 12, the phenolic compounds: ayanin, 2,6-dimethoxybenzoic acid, methyl 3,4-dihydroxycinnamate, chlorogenic acid, and 3,5-dicaffeoylquinic acid were also isolated. The structures of these compounds were determined by spectroscopic methods and chemical reactions. The antibacterial and antifungal activities of compounds 1 - 12 were evaluated on Staphylococcus aureus, Escherichia coli, and Candida albicans. Deltoidin A (11) was the most active antibacterial agent (MIC 16.0 µg ml-1 ) against E. coli, and the ent-kaurenoid derivatives (1 - 2) showed activity (MIC 31.0 µg ml-1 ) against S. aureus.

Phytochemical Composition and Biological Activities of Dyssodia tagetiflora Lag.

While plants of the genus Dyssodia are used by man to a certain extent, few phytochemical and pharmacological studies have been performed with species of this genus. D. tagetiflora is an endemic plant of Mexico and has been used as fodder. The aim of this research was to isolate and identify the main bioactive components and evaluate the insecticidal, antioxidant, genotoxic and cytoprotective activities of D. tagetiflora. The isolated substances included an essential oil composed of six monoterpenes, and extracts containing two flavonols, three flavonol-glycosides and four thiophenes. The compounds were characterized using spectroscopic and spectrometric methods, including GC/MS, MS and NMR. The essential oil showed insecticidal activity against Drosophila melanogaster larvae. The methanolic extract of D. tagetiflora (DTME) had strong antioxidant activity against DPPH and ABTS radicals; DTME showed no evidence of genotoxic or cytotoxic effects. In contrast, DTME showed a cytoprotective effect attenuating the formation of H2 O2 -induced micronuclei in Vicia faba roots. This report is the first to describe the phytochemical and biological activity of D. tagetiflora.

Terpenoids from Melampodium perfoliatum.

The phytochemical study of the aerial parts of Melampodium perfoliatum afforded six melampolides (1, 3, 5-8), a eudesmanolide (9), two diterpene lactones (10, 11), and two ent-kaurane derivatives (12, 13), together with the known melampodin (2) and polymatin A (4). The structures of the compounds were elucidated by physical data analysis and chemical reactions. Compounds 2, 4, 5, and 10 exhibited dose-dependent anti-inflammatory activity on the 12-O-tetradecanoylphorbol-13-acetate-induced ear edema model, with ID50 values of 1.14, 0.56, 1.15, and 1.49 µmol/ear, respectively, compared to the reference compound indomethacin (0.24 µmol/ear).

Sesquiterpenoids from Pittocaulon filare.

The phytochemical study of Pittocaulon filare afforded three oplopanes (1-3), a eudesmane (6), and three oplopane glucosides (7-9), one of them reported as its acetyl derivative (7a), together with several known compounds. The structures of the compounds were elucidated by spectroscopic analysis and chemical reactions. The anti-inflammatory activity of compounds 1-5 was determined using the 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema model, and the effect of compounds 1-4 on the recruitment of neutrophils was evaluated using the myeloperoxidase test. Compounds 1 and 2 were the more active anti-inflammatory agents, with lower ID50 values (0.17 and 0.18 µmol/ear, respectively) than indomethacin (0.24 µmol/ear), but they had a lesser effect on the inhibition of neutrophil infiltration than both indomethacin and compound 3, indicating that the tested compounds do not have the same ability to inhibit edema and to prevent cell infiltration.

Chemical composition and biological activity of Laennecia schiedeana.

The chemical study of Laennecia schiedeana afforded three sterols, five diterpenes, five flavonoids, three caffeoyl derivatives of quinic acid, and two triterpenes. Evaluation of the cytotoxic activity of the extracts and isolated metabolites showed that 15-methoxy-16-oxo-15,16H-strictic acid was the most active compound [(15.05 +/- 2.2) microg/mL against U-251 cells]. In antibacterial assays the acetonic extract of leaves was the only active extract exhibiting its highest effect against the multiresistant Staphylococcus epidermidis (MIC 0.25 mg/mL). The anti-inflammatory activity observed was mild in the extracts and not relevant in the isolated compounds.

Seco-eremophiladiolides and eremophilane glucosides from Pittocaulon velatum.

Two seco-eremophiladiolides, velatumolide and epi-velatumolide, the trihydroxyfuranoeremophilane velatumin, and three eremophilane glucosides were isolated from Pittocaulon velatum, together with several known compounds. The structures of these compounds were elucidated by spectroscopic analysis and chemical reactions. The anti-inflammatory activity of the isolated compounds was investigated using the TPA-induced ear edema model.

Chemical constituents of Roldana lineolata.

The new eremophilanolide 1, the known eremophilane derivatives 2 and 3, already described as part of mixtures, the known compounds hyperin, 2''-acetylhyperin and two calenduladiol esters were isolated from Roldana lineolata. Their structures were determined by spectroscopic methods. Compounds 1 and 2 as well as their acetylated and oxidized derivatives were tested against several fungi strains. Eremophilanolide 1 showed a mild activity against Trichophyton mentagrophytes.

Cacalol derivatives from Roldana angulifolia.

Four new modified eremophilanes, angulifolide (1) and angulifolins A-C (2-4), and two new triacetylglucosides (7 and 8) were isolated from Roldana angulifolia, together with several known compounds. The structures of the new compounds were elucidated by spectroscopic analysis and chemical reactions. The absolute configuration of compounds 2 and 3 was established by Mosher ester methodology. Cytotoxicity against selected human cancer cell lines was determined for the more abundant isolated metabolites.

Eremophilanes from Senecio mairetianus and some reaction products.

Eight new eremophilanolides (1, 2, 4-7, 9, and 10), a new eremophilane (13), and several known compounds were isolated from the roots and aerial parts of Senecio mairetianus. The chemical structures were proposed taking into consideration spectroscopic analyses and chemical transformations. X-ray diffraction analysis of 2, 4, and 9 confirmed their structures. The stereochemistry of 1,10-epoxy-8alpha-methoxyermophilanolide (3) was determined. Compounds 4-7, 9, and 10 are possible artifacts obtained by preparation of the alkaloidal extract.

Eremophilane esters of Robinsonecio gerberifolius and their rearranged products. Study of the coupling constants (2)J(H, H), (3)J(H, H) and (4)J(H, H).

In the course of the basic hydrolysis of four eremophilane esters isolated from Robinsonecio gerberifolius, some rearrangements, eliminations, and additions occurred. Five compounds were obtained, three of them not previously described. Additionally, a new sesquiterpene was produced by autooxidation of compound 1. The (1)H and (13)C NMR spectra of these compounds were completely assigned by utilization of HMQC, HMBC, COSY, DEPT, and NOESY techniques. The long-range coupling constants of the peroxide 10 are reported, and all its coupling constants (2)J(H, H), (3)J(H, H), and (4)J(H, H) are calculated at the B3LYP/6-31G(d,p) level of theory. Their magnitude is explained in terms of electronic delocalization and the additivity of stereoelectronic effects.

Insect growth inhibition by tocotrienols and hydroquinones from Roldana barba-johannis.

The methanol extract from the aerial parts of Roldana barba-johannis (Asteraceae) afforded sargachromenol, sargahydroquinoic acid, and sargaquinoic acid. These natural products and their corresponding acetylated and methylated derivatives showed insecticidal and insect growth regulatory activities against the Fall Armyworm [Spodoptera frugiperda J.E. Smith, (Lepidoptera: Noctuidae)], an important insect pest of corn. The most active compounds were sargachromenol and its acetylated derivative; sargahydroquinoic acid and its acetylated derivative; and a mixture of sargachromenol, sargahydroquinoic acid, and sargaquinoic acid (6:3:1) and the acetylated form of this mixture. All these compounds and mixtures had significant inhibitory effects between 5.0 and 20.0 ppm in diets. Most compounds were insecticidal to larvae, with lethal doses between 20 and 35 ppm. In addition, these substances also demonstrated scavenging properties toward 2,2-diphenyl-1-picrylhydrazyl radical in TLC autographic and spectrophotometric assays. These compounds appear to have selective effects on the pre-emergence metabolism of the insect. The results from these compounds were fully comparable in activity to those known natural insect growth inhibitors such as gedunin and methanol extracts of Cedrela salvadorensis and Yucca periculosa. These substances may be useful as natural insecticidal agents.

New oplopane and eremophilane derivatives from Robinsonecio gerberifolius.

A phytochemical study of Robinsonecio gerberifolius afforded six new sesquiterpenoids, two oplopane (1and 2) and four eremophilane derivatives (3-6). The structures of these compounds were elucidated on spectroscopic grounds, and the absolute configurations of compounds 3 and 4 were established from CD analysis. The known 3beta-angeloyloxy-1,10-epoxyfuranoeremophilane (7) was also isolated, and its stereochemistry was revised. The cytotoxic activities of compounds 1-7 were determined against five human cancer cell lines.

Evaluation of the anti-inflammatory and antioxidant activities of the plastoquinone derivatives isolated from Roldana barba-johannis.

A phytochemical study of Roldana barba-johannis afforded two triterpenic esters, an eremophilanolide and three compounds structurally related to the antioxidants vitamin E and plastoquinone. Evaluation of the anti-inflammatory and antioxidant activities of sargahydroquinoic acid, sargachromenol, their mixture, and their methyl esters showed that most of them are antioxidant and anti-inflammatory agents.