Silvia H. Taleb-Contini

Antimicrobial activity of flavonoids and steroids isolated from two Chromolaena species

The crude extracts (dichloromethanic and ethanolic) and some compounds (8 flavonoids and 5 steroids) isolated from Chromolaena squalida (leaves and stems) and Chromolaena hirsuta (leaves and flowers) have been evaluated against 22 strains of microorganisms including bacteria (Gram-positive and Gram-negative) and yeasts. All crude extracts, flavonoids and steroids evaluated have been shown actives, mainly against Gram-positive bacteria.

Differences in secondary metabolites from leaf extracts of Mikania glomerata Sprengel obtained by micropropagation and cuttings

GC analysis of the dichloromethane extracts obtained from cultivated specimens of Mikania glomerata Sprengel possibilited to verify that cuttings technique led to production of kaurenoic acid and coumarin while the same results have not been observed by propagation process using in vitro techniques.

An ent-kaurane-type diterpene in Croton antisyphiliticus mart.

Croton antisyphiliticus is a medicinal plant widely used in the treatment of microbial infections, especially those affecting the genital tract. Crude extract, fractions and pure compound isolated from roots of this species were investigated to validate their antimicrobial activity against Escherichia coli and Staphylococcus aureus. The compound ent-kaur-16-en-18-oic acid was isolated as a major component (0.7% of crude extract), and its MIC value determined against S. aureus (ATCC 6538) was 250 μg/mL. This is the first phytochemical work on the species monitored with antimicrobial assay.

7-Hydroxycoumarin modulates the oxidative metabolism, degranulation and microbial killing of human neutrophils

In the present study, we assessed whether 7-hydroxycoumarin (umbelliferone), 7-hydroxy-4-methylcoumarin, and their acetylated analogs modulate some of the effector functions of human neutrophils and display antioxidant activity. These compounds decreased the ability of neutrophils to generate superoxide anion, release primary granule enzymes, and kill Candida albicans. Cytotoxicity did not mediate their inhibitory effect, at least under the assessed conditions. These coumarins scavenged hypochlorous acid and protected ascorbic acid from electrochemical oxidation in cell-free systems. On the other hand, the four coumarins increased the luminol-enhanced chemiluminescence of human neutrophils stimulated with phorbol-12-myristate-13-acetate and serum-opsonized zymosan. Oxidation of the hydroxylated coumarins by the neutrophil myeloperoxidase produced highly reactive coumarin radical intermediates, which mediated the prooxidant effect observed in the luminol-enhanced chemiluminescence assay. These species also oxidized ascorbic acid and the spin traps α-(4-pyridyl-1-oxide)-N-tert-butylnitrone and 5-dimethyl-1-pyrroline-N-oxide. Therefore, 7-hydroxycoumarin and the derivatives investigated here were able to modulate the effector functions of human neutrophils and scavenge reactive oxidizing species; they also generated reactive coumarin derivatives in the presence of myeloperoxidase. Acetylation of the free hydroxyl group, but not addition of the 4-methyl group, suppressed the biological effects of 7-hydroxycoumarin. These findings help clarify how 7-hydroxycoumarin acts on neutrophils to produce relevant anti-inflammatory effects.

Neuropharmacological Effects in Mice of Lychnophora Species (Vernonieae, Asteraceae) and Anticonvulsant Activity of 4,5-di-O-(E)-caffeoylquinic Acid Isolated From the Stem of L. rupestris and L. staavioides

Aiming at contributing with the search for neuroactive substances from natural sources, we report for the first time antinociceptive and anticonvulsant effects of some Lychnophora species. We verify the protective effects of polar extracts (600 mg/kg, intraperitoneally), and methanolic fractions of L. staavioides and L. rupestris (100 mg/kg, intraperitoneally) in pentylenetetrazole-induced seizures on mice. Previously, a screening was accomplished, evaluating the antinociceptive central activity (hot plate test), with different extracts of L. rupestris, L. staavioides and L. diamantinana. It was possible to select the possible extracts of Lychnophora with central nervous system activity. Some of the active extracts were submitted to fractionation and purification process and the methanolic fractions of L. rupestris (stem) and L. staavioides (stem), with anticonvulsant properties (100 mg/kg, intraperitoneally), yielded 4,5-di-O-[E]-caffeoylquinic acid. This substance was injected intraperitoneally in mice and showed anticonvulsant effect against pentylenetetrazole-induced seizures at doses of 25 and 50 mg/kg. It has often been shown that seizures induced by pentylenetetrazole are involved in inhibition and/or attenuation of GABAergic neurotransmission. However, other systems of the central nervous system such as adenosinergic and glutamatergic could be involved in the caffeoylquinic acid effects. Further studies should be conducted to verify that the target receptor could be participating in this anticonvulsant property. Although other investigations have reported a series of biological activities from Lychnophora species, this is the first report of central analgesic and anticonvulsant activity in species of this genus.

Eugenia punicifolia (Kunth) DC. as an Adjuvant Treatment for Type-2 Diabetes Mellitus: A non-Controlled, Pilot Study

Type‐2 diabetes mellitus (DM) is a highly prevalent disease with significant morbidity and mortality around the world. However, there is no universally effective treatment, because response to different treatment regimens can vary widely among patients. In this study, we aimed to investigate whether the use of the powdered dried leaves of Eugenia punicifolia (Kunth) DC. (Myrtaceae) is effective as an adjuvant to the treatment of patients with type‐2 DM. Fifteen patients were enrolled in a pilot, non‐controlled study, and received E. punicifolia for 3 months. After treatment, we observed a significant decrease in glycosylated hemoglobin, basal insulin, thyroid‐stimulating hormone, C‐reactive protein, and both systolic and diastolic blood pressure. There were no changes in fasting and postprandial glycemia. The compounds myricetin‐3‐O‐rhamnoside, quercetin‐3‐O‐galactoside, quercetin‐3‐O‐xyloside, quercetin‐3‐O‐rhamnoside, kaempferol‐3‐O‐rhamnoside, phytol, gallic acid, and trans‐caryophyllene present in the powdered dried leaves of E. punicifolia may be responsible for the therapeutic effect. In conclusion, the powdered leaves of E. punicifolia are promising as an adjuvant in the treatment of type‐2 DM and deserve further investigation. Copyright

4-methylcoumarin derivatives inhibit human neutrophil oxidative metabolism and elastase activity.

Increased neutrophil activation significantly contributes to the tissue damage in inflammatory illnesses; this phenomenon has motivated the search for new compounds to modulate their effector functions. Coumarins are natural products that are widely consumed in the human diet. We have evaluated the antioxidant and immunomodulator potential of five 4-methylcoumarin derivatives. We found that the 4-methylcoumarin derivatives inhibited the generation of reactive oxygen species by human neutrophils triggered by serum-opsonized zymosan or phorbol-12-myristate-13-acetate; this inhibition occurred in a concentration-dependent manner, as revealed by lucigenin- and luminol-enhanced chemiluminescence assays. Cytotoxicity did not mediate this inhibitory effect. The 7,8-dihydroxy-4-methylcoumarin suppressed the neutrophil oxidative metabolism more effectively than the 6,7- and 5,7-dihydroxy-4-methylcoumarins, but the 5,7- and 7,8-diacetoxy-4-methylcoumarins were less effective than their hydroxylated counterparts. An analysis of the biochemical pathways suggested that the 6,7- and 7,8-dihydroxy-4-methylcoumarins inhibit the protein kinase C-mediated signaling pathway, but 5,7-dihydroxy-4-methylcoumarin, as well as 5,7- and 7,8-diacetoxy-4-methylcoumarins do not significantly interfere in this pathway of the activation of the human neutrophil oxidative metabolism. The 4-methylcoumarin derivatives bearing the catechol group suppressed the elastase and myeloperoxidase activity and reduced the 1,1-diphenyl-2-picrylhydrazyl free radical the most strongly. Interestingly, the 5,7-dihydroxy-4-methylcoumarin scavenged hypochlorous acid more effectively than the o-dihydroxy-substituted 4-methylcoumarin derivatives, and the diacetoxylated 4-methylcoumarin derivatives scavenged hypochlorous acid as effectively as the 7,8-dihydroxy-4-methylcoumarin. The significant influence of small structural modifications in the inhibitory potential of 4-methylcoumarin derivatives on the effector functions of neutrophil makes them interesting candidates to develop new drugs for the treatment of inflammatory diseases mediated by increased neutrophil activation.

Isolation of flavonoids from Anemopaegma arvense (Vell) Stellf. ex de Souza and their antifungal activity against Trichophyton rubrum

Anemopaegma arvense pertence a familia Bignoniaceae, sendo conhecida popularmente como Catuaba. Para avaliacao de sua atividade citotoxica e antimicrobiana, a fracao cromatografica F3 e os flavonoides 1 (quercetina 3-O-α-L-ramnopiranosil-(1→6)-β-D-glucopiranosideo) (rutina) e flavonoide 2 (quercetina 3-O-α-L-ramnopiranosil-(1→6)-β-D-galactopiranosideo) foram isolados das folhas de A. arvense. A fracao 3 e os flavonoides nao apresentaram atividade antibacteriana. Nenhuma atividade citotoxica foi observada para a fracao F3 e para os flavonoides, quando avaliados contra as celulas tumorais em teste. Entretanto, e considerando a atividade antifungica, o flavonoide 1 apresentou valor de concentracao inibitoria minima (CIM) de 0,5 mg/mL, enquanto o flavonoide 2, CIM de 0,25 mg/mL contra as cepas selvagem e mutante de Trichophyton rubrum, demonstrando, pela primeira vez, que os flavonoides isolados possuem atividade antifungica, o que valida a mesma atividade para A. arvense.

Detection of flavonoids in glandular trichomes of Chromolaena species (Eupatorieae, Asteraceae) by reversed-phase high-performance liquid chromatography

In this work, twelve flavonoids were detected in glandular trichomes of two species of Chromolaena through the glandular microsampling technique and HPLC-UV-DAD analysis. This is the first time that the accumulation of flavonoids in glandular trichomes of the genus Chromolaena is reported. Based on the results, we suggest that this technique can be an useful tool in the search of new compounds with medicinal properties as well as in chemotaxonomic studies of Eupatorieae.

Estudo fitoquímico de Mikania pseudohoffmanianna G. M. Barroso ex W. C. Holmes

This work describes the fractionation of methanol and dichloromethane extracts of aerial parts from the Mikania pseudohoffmanniana G. M. Barroso ex W. C. Holmes. The phytochemical study of extracts led to isolation and the identification of 16 known compounds, including: steroids: campesterol, stigmasterol and b-sitosterol, diterpenes: ent-15b-E-cinnamoyloxy-kaur-16-en-19-oic acid, ent-15b-Z-cinnamoyloxy-kaur-16-en-19-oic acid and ent-kaur-16-en-19-oic acid, triterpenes: a-amyrin, b-amyrin, a-amyrin acetate, b-amyrin acetate, lupeol, lupeol acetate and friedelin, coumarin: scopoletin, flavonoid: quercetin and caffeoyl quinic acid derivative: 4,5-di-O-[E]-caffeoyl quinic acid.