Naphthoquinones of Sinningia reitzii and Anti-inflammatory/Antinociceptive Activities of 8-Hydroxydehydrodunnione.

Chemical investigation of the tubers of Sinningia reitzii led to the isolation of five new naphthoquinones, 8-hydroxydehydrodunnione (1), 7-hydroxydehydrodunnione (2), 5-hydroxy-6,7-dimethoxy-α-dunnione (3), 5-hydroxy-6,7-dimethoxydunniol (4), and 8-hydroxy-7-methoxy-2-O-methylstreptocarpone (5). Three known naphthoquinones, 7-hydroxy-α-dunnione, 8-hydroxydunnione, and 6,8-dihydroxy-7-methoxy-2-O-methyldunniol, were also identified. When tested for anti-inflammatory activity in a mouse model, compound 1 (50-500 pg/paw) reduced the edema induced by carrageenan in a dose-dependent fashion. The highest dose showed a similar inhibition to that observed for the positive control dexamethasone. At lower doses (5-10 pg/paw), 1 also dose dependently reduced the mechanical hyperalgesia induced by carrageenan. Compound 1 (15 pg/paw) abolished the mechanical hyperalgesia induced by prostaglandin E2 and dopamine, but not that induced by dibutyryl cyclic AMP. Dipyrone (320 µg/paw) completely abolished the hyperalgesia induced by these algogens. Additionally, compound 1 did not alter heat-induced nociception. These results suggest that this new naphthoquinone exhibits important anti-inflammatory and antinociceptive activities, which is dissimilar to that of most known analgesics.

1H HR-MAS NMR chemical profile and chemometric analysis as a tool for quality control of different cultivars of green tea (Camellia sinensis).

Green tea is a product obtained from the processing of fresh leaves of Camellia sinensis (L.) O. Kuntze species. In this study, the influence of climatic parameters on the chemical composition of green tea cultivars ('Yabukita' and 'Yutakamidori') over the harvest was evaluated using HR-MAS NMR. 'Yabukita' showed higher concentrations of epicatechin while higher amounts of theanine and caffeine were found in 'Yutakamidori'. The decline of theanine was associated with high average maximum temperature and solar radiation index, this latter also seemed to be responsible for relevant changes in epicatechin concentrations. It was not possible to associate any trend between climatic parameters and caffeine concentration. Fluctuations in linolenic acid concentration were monitored during the harvest period and were associated with the plant's defense mechanism. Monitoring of green tea over seasons and correlating the fluctuations of compounds to climatic parameters might become an efficient strategy for establishing quality standards for green teas.

Bioactivity-guided isolation of cytotoxic sesquiterpene lactones of Gochnatia polymorpha ssp. floccosa.

Phytochemical study of Gochnatia polymorpha (Less) Cabr. ssp. floccosa Cabr. trunk bark, guided by antiproliferative assays on 10 human cancer cell lines and the VERO cell line, yielded six known compounds identified as the triterpene bauerenyl acetate, the guaianolide 11α,13-dihydrozaluzanin C and the dimeric guaianolides 10-desoxygochnatiolide A, gochnatiolide A, 8-hydroxi-10-desoxygochnatiolide A and 8-hydroxigochnatiolide A. Extracts, fractions of extracts and isolated compounds were tested in vitro against a panel of human cancer cell lines, including U251 (glioma, CNS), UACC-62 (melanoma), MCF-7 (breast), NCI-ADR/RES (drug-resistant ovarian), 786.0 (kidney), NCI-H460 (lung, no small cells), PC-3 (prostate), OVCAR-3 (ovarian), HT-29 (colon), K562 (leukemia) and against the VERO no cancer cell line. Bauerenyl acetate was inactive, while 11α,13-dihydrozaluzanin C showed weak activity against UACC62 and the VERO cell line. The most active compounds were 10-desoxygochnatiolide A and gochnatiolide A, which inhibited the growth of kidney, melanoma, ovarian-resistant and glioma cell lines with values of TGI (total growth inhibition) varying 0.21-1.09 µg/mL. This is the first report about cytotoxic activity of dimeric lactones against cell lines.

Lactones and quinones from the tubers of Sinningia aggregata.

Three new aromatic epsilon-lactones, aggregatins A (1), B (2), and C (3), a new naphthoquinone derivative, aggregatin D (4), and three known anthraquinones, 2-methylanthraquinone, 7-methoxy-2-methylanthraquinone, and 7-hydroxy-2-methylanthraquinone, were isolated from the tubers of Sinningia aggregata (Gesneriaceae). Compounds 1 and 4 and the anthraquinones showed marginal antimicrobial activity.

Constituents of the leaves of Magnolia ovata.

Two new lignans, magnovatins A (1) and B (2), along with nine known compounds, were isolated from the leaves of Magnolia ovata. The known compounds were identified as acuminatin (3), licarin A (4), kadsurenin M, 4-O-demethylkadsurenin M, oleiferin A, oleiferin C, spathulenol, parthenolide, and 11,13-dehydrocompressanolide. In addition, compounds 1 and 2 yielded four new derivatives (1a, 1b, 2a, and 2b). The structures of the new compounds were established on the basis of spectrometric data evaluation. Free-radical scavenging and antimicrobial activities of the major compunds 1, 3, and 4 were investigated.

A Naphthoquinone from Sinningia canescens Inhibits Inflammation and Fever in Mice.

We previously showed that plants from the genus Sinningia are a source of antiinflammatory and analgesic compounds with different mechanisms of action. The present study evaluated the antiinflammatory, antinociceptive, and antipyretic effects of a crude extract (CE) from Sinningia canescens, its fractions, and 6-methoxy-7-hydroxy-α-dunnione (MHD) in mice. These effects were evaluated using carrageenan (Cg)-induced paw edema, acetic acid- and formalin-induced nociception, mechanical hyperalgesia, lipopolysaccharide (LPS)-induced fever, and plasma cytokine levels. The CE and dichloromethane and hexane fractions reduced Cg-induced paw edema and hyperalgesia, LPS-induced fever, and plasma tumor necrosis factor-α (TNF-α) levels. The CE also reduced acetic acid-induced writhing and the second phase of formalin-induced nociception but did not alter thermal nociception or motor performance. Partition with solvents showed that the antiinflammatory, antihyperalgesic, and antipyretic activities were present in dichoromethane and hexane fractions, and the major compound isolated from these fractions was MHD. Oral and intraplantar MHD administration reduced paw edema. Oral MHD administration also reduced prostaglandin E2-induced hyperalgesia but did not alter hyperalgesia that was induced by dopamine and dibutyryl cyclic adenosine monophosphate. Treatment with glibenclamide, a KATP channel blocker, did not alter the analgesic effect of MHD. Lipopolysaccharide-induced fever and TNF-α, interleukin-1ß, and interleukin-6 levels were inhibited by MHD. Altogether, these data suggest that the CE has antiinflammatory, analgesic, and antipyretic activity, and these actions are at least partially related to MHD. These results also suggest that MHD acts by blocking cytokine synthesis and/or blocking prostaglandin activity.

A new naphthoquinone from Sinningia leucotricha (Gesneriaceae).

A new naphthoquinone, 7,8-dimethoxydunnione (1), was isolated from Sinningia leucotricha (Hoehne) Moore tubers, together with four known compounds: 7- hydroxy-t-dunnione (2), 6-methoxy-7-hydroxy-a-dunnione (3), presilphiperfolan-9-ol (4), and betulinic acid (5). All compounds were identified by spectroscopic and mass spectrometric techniques and comparison with literature data. Compounds 2-5 are being reported for the first time in S. leucotricha.

New neolignans from Talauma ovata.

The hexane extract of the bark of Talauma ovata yielded three new natural neolignans, identified as acetyl oleiferin-C (4), acetyl oleiferin-F (7) and acetyl oleiferin-G (8), together with the known compounds dihydroguaiaretic acid (1), austrobailignan-5 (2), oleiferin-C (3), austrobailignan-6 (5) and oleiferin-F (6).

A new sesquiterpene lactone and other constituents of Moquiniastrum polymorphum subsp. floccosum (Asteraceae).

A new guaianolide, 1S, 3S, 5R, 6S, 7S, 11R-l-hydroxy-11α,13-dihydrozaluzanin C (1), was isolated from Moquiniastrum polymorphum subsp. floccosum trunk bark, together with fifteen known compounds, which were identified as 11α,13-dihydroglucozaluzanin C (2), 8α-hydroxy-11α,13-dihydrozaluzanin C (3), zaluzanin C (4), gochnatiolide B (5), ethyl caffeate (6), methyl chlorogenate (7), ethyl chlorogenate (8), methyl 3,5-dicaffeoyl quinate (9), ethyl 3,5-dicaffeoyl quinate (10), methyl 4,5-dicaffeoyl quinate (11), ethyl 4,5-dicaffeoyl quinate (12), ethyl 3,4-dicaffeoyl quinate (13), 3,5-dicaffeoyl quinic acid (14), 4,5-dicaffeoyl quinic acid (15), and 3,4-dicaffeoyl quinic acid (16). With the exception of 5, all known compounds are being reported for the first time in M. polymorphum.

Antinociceptive and anti-inflammatory activities of the ethanolic extract, fractions and 8-methoxylapachenol from Sinningia allagophylla tubers.

This study investigated the antinociceptive and anti-inflammatory activities of the ethanolic extract (EESAl), fractions and the compound 8-methoxylapachenol (8ML) obtained from the tubers of Sinningia allagophylla. Male Swiss mice were treated with EESAl (3-300 mg/kg) or vehicle by oral route (p.o.) 1 hr before the injection of formalin 2.5% or carrageenan (Cg) into the hind paw. EESAl (3-30 mg/kg) reduced the inflammatory phase of the nociceptive behaviour induced by formalin (around 65% for all doses). EESAl (3-300 mg/kg, p.o.) also reduced Cg-induced mechanical hyperalgesia and oedema in a dose-dependent fashion but did not change the hot-plate latency or the motor performance of the animals. Oral administration of petroleum ether fraction (PE, 3 mg/kg), but not in the methanolic fraction (30 mg/kg), reduced both Cg-induced oedema and hyperalgesia. Compound 8ML isolated from PE (1.8 mg/kg, p.o.) abolished Cg-induced hyperalgesia but also did not change hot-plate latency or motor performance of the animals. 8ML administration into the paw (0.75-750 pg) dose-dependently reduced Cg-induced hyperalgesia. 8ML (750 pg) also blocked the hyperalgesia induced by tumour necrosis factor (TNF-α), interleukin-1ß (IL-1ß) and prostaglandin E2 (PGE2 ) but failed to change the hyperalgesia induced by cytokine-induced neutrophil chemoattractant-1 (CINC-1) and dopamine (Dopa). These results suggest that EESAl has an important antinociceptive and anti-inflammatory activity, the former one related, at least in part, to the reduction in the hyperalgesia. Similarly, 8ML reduced Cg-induced oedema and mechanical hyperalgesia and seems to act in peripheral sites and on the prostaglandin rather than on the sympathetic component of the Cg-inflammatory hyperalgesia.

Essential oil and other constituents from Magnolia ovata fruit.

The volatile and non-volatile constituents of the unripe fruits of Magnolia ovata (A. St.-Hil.) Spreng. (Magnoliaceae) were studied. The essential oils were obtained by hydrodistillation of the fruit of two plant populations (A and B) and analyzed by GC/FID and GC/MS. The oil of sample A was rich in sesquiterpenes, mainly spathulenol (19.3%), while the oil of sample B showed a predominance of aliphatic compounds, mainly hexadecanoic acid (52.0%). Extracts of the dried fruit contained fourteen known compounds including nine lignoids (magnovatin A, magnovatin B, acuminatin, licarin A, oleiferin A, oleiferin C, kadsurenin M, 4-O-demethylkadsurenim M and 7-epi-virolin), two sesquiterpene lactones (parthenolide and michelenolide) and three alkaloids (lysicamine, lanuginosine and O-methylmoschatoline). Michelenolide, 7-epi-virolin and lisycamine are reported for the first time in the species, while the remaining compounds have already been reported in the leaves and/or trunk bark o f Magnolia ovata. Acetylation o f oleiferin A yielded a ne wcompound, acetyl oleiferin A, whose NMR data and that of michelenolide are furnished.

Triterpenes from the flowers of Gochnatia polymorpha subsp. floccosa

Phytochemical study of the flowers of Gochnatia polymorpha subsp. floccosa, Asteraceae, yielded eleven known triterpenes identified as lupeol, lupeyl acetate, lupeyl palmitate, taraxasterol, taraxasteryl acetate, pseudotaraxasterol, pseudotaraxasterol acetate, α-amyrin, α-amyryl palmitate, β-amyrin and β-amyryl palmitate, along with sitosterol, stigmasterol, palmitic and stearic acids. These compounds are been reported for the first time in the species. The compounds were identified by analysis of NMR spectra (¹H, 13C and DEPT), GC-MS and comparison with literature data. Previous work have reported the isolation of triterpenes, diterpenes, sesquiterpenes, flavonoids, coumarins and phenolic compounds from aerial parts and roots from G. polymorpha.

Avaliação da atividade antimicrobiana e citotóxica de extratos de Gochnatia polymorpha ssp floccosa / Evaluation of antimicrobial and cytotoxic activitiy of extracts from Gochnatia polymorpha (Less) ssp floccosa

Neste estudo procedeu-se a avaliação da atividade antimicrobiana e citotóxica de extratos de Gochnatia polymorpha ssp floccosa, espécie empregada na medicina popular contra doenças respiratórias. Folhas, cascas do tronco e ramos foram extraídos com hexano, diclorometano e etanol, sucessivamente, sendo obtidos os respectivos extratos brutos. A atividade antimicrobiana foi determinada pelo método de difusão em ágar utilizando-se bactérias Gram-positivas, Gram-negativas e fungos. A avaliação da citotoxicidade foi realizada empregando-se o ensaio de letalidade contra Artemia salina. Nenhum dos extratos mostrou atividade citotóxica. Os extratos das folhas apresentaram uma fraca atividade antimicrobiana frente a algumas cepas de Staphylococcus aureus e Streptococcus mutans, enquanto o extrato em diclorometano dos ramos e o extrato em etanol das cascas foram ativos contra Micrococcus luteus, Staphylococcus aureus e S. epidermidis. A maior atividade antimicrobiana foi observada para o extrato em diclorometano das cascas, que inibiu o crescimento de Micrococcus luteus, Staphylococcus aureus, S. epidermidis, Streptococcus mutans, Enterococcus faecalis e Candida albicans. Esta atividade parece estar relacionada à presença de diterpenos no extrato. Nenhum dos extratos estudados (a 5,0 mg/mL) mostrou atividade frente a cepas de bactérias Gram-negativas. Esses resultados demonstram o potencial dessa planta como fonte de compostos antibacterianos e justificam, parcialmente, seu uso popular.

The antimicrobial and cytotoxic activities of Gochnatia polymorpha ssp floccosa, a medicinal plant used against respiratory diseases, were evaluated. Successive petroleum ether, dichloromethane and ethanol extracts of dried leaves, trunk bark and stems were used in the brine shrimp lethality bioassay and tested against 22 strains of microorganisms (Gram-positive and Gram-negative bacteria and fungi) by the well-diffusion agar method. None of the extracts showed cytotoxicity on the brine shrimp bioassay. The extracts of leaves showed a mild activity against some strains of Staphylococcus aureus and Streptococcus mutans. The ethanol extracts of trunk bark and dichloromethane extract of stems also showed activity against Micrococcus luteus, Staphylococcus aureus and S. epidermidis. The highest activity was found in the dichloromethane extract of trunk bark, which showed significant antibacterial and antifungal activities against Micrococcus luteus, Staphylococcus aureus, S. epidermidis, Streptococcus mutans, Enterococcus faecalis and Candida albicans. Diterpenes are present in this extract and could be responsible for the activity. All the screened extracts were shown to be inactive (at 5.0 mg/mL) against strains of Gram-negative bacteria tested. These results indicate the potential of G. polymorpha ssp floccosa as a source of antibacterial compounds and partly support the use of this plant in folk medicine.

Comparative ethnopharmacology: a rational method for the search of bioactive compounds in plants

In the present preliminary communication on comparative ethnopharmacology a limited universe of data extracted from the Journalo od Ethnopharmacology (vols.1025) was used for the construction of ethnopharmacological profiles of ten families of dicotyledons. Intraprofile analysis suggested the main uses of plant species (infdcated by the maximal citation frequencies), as opposed to the spurious ones (represented by base line fluctuations), to possess a solid chemotaxonomic basis. Interprofile analysis via correlation of ethnopharmacological distances and morphological (evolutionary) distances among the same plant families suggested compartive ethnopharmacology to possess also a phylogenetic (chemosystematic) basis. This result establishes comparative ethnopharmacology as a novel and potentially useful scientific discipline