Mary Ann Foglio

Antiulcerogenic activity of crude hydroalcoholic extract of Rosmarinus officinalis L.

Rosmarinus officinalis L. crude hydroalcoholic (70%) extract was evaluated for antiulcerogenic activity employing different experimental models. The crude hydroalcoholic extract (CHE) decreased the ulcerative lesion index produced by indomethacin, ethanol and reserpine in rats. No antisecretory activity was observed on pyloric ligation model. The previous administration of L-NAME, a NO-synthase inhibitor, did not reduce the antiulcerogenic activity of CHE in ethanol induced ulcer model, suggesting that the pharmacological mechanism has no relationship with nitric oxide (NO). Whereas when the animal groups were treated with indomethacin, using the same experimental model, CHE did not reduce the antiulcerogenic activity, suggesting that the pharmacological mechanism has no relationship with prostaglandins. The previous treatment with N-ethymaleimide, a thiol blocker, including mucosal nonprotein sulfhydryl groups, reduced the anitulcerogenic activity of CHE on ethanol induced ulcer model. This result suggests that the crude hydroalcoholic extract of R. officinalis L. has active substances that increase the mucosal nonprotein sulfhydryl groups content. In another hypothesis, the pharmacological mechanism could be attributed to the activity of antioxidant compounds found in the crude hydroalcoholic extract which can react with N-ethylmaleimide.

Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) β-carboline derivatives

Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50)<100 microM) for all eight different types of human cancer cell lines tested. The beta-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI(50) values lying in the nanomolar concentration range (GI(50)=10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50)=0.06 microM), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents.

Antimicrobial potential of some plant extracts against Candida species

The increase in the resistance to antimicrobial drugs in use has attracted the attention of the scientific community, and medicinal plants have been extensively studied as alternative agents for the prevention of infections. The Candida genus yeast can become an opportunistic pathogen causing disease in immunosuppressive hosts. The purpose of this study was to evaluate dichloromethane and methanol extracts from Mentha piperita, Rosmarinus officinalis, Arrabidaea chica, Tabebuia avellanedae, Punica granatum and Syzygium cumini against Candida species through the analysis of Minimum Inhibitory Concentration (MIC). Results presented activity of these extracts against Candida species, especially the methanol extract.

Evaluation of wound healing properties of Arrabidaea chica Verlot extract.

ETHNOPHARMACOLOGICAL RELEVANCE Arrabidaea chica Verlot. (Bignoniaceae), popularly known as Crajiru, has been traditionally used as wound healing agent. AIM OF THE STUDY Investigate in vitro and in vivo healing properties of Arrabidaea chica leaves extract (AC). MATERIALS AND METHODS AC was evaluated in vitro in fibroblast growth stimulation (0.25-250 microg/mL) and collagen production stimulation (250 microg/mL) assays. Allantoin (0.25-250 microg/mL) and vitamin C (25 microg/mL) were used as controls respectively. DPPH and Folin-Ciocalteau assays were used for antioxidant evaluation, using trolox (0.25-250 microg/mL) as reference antioxidant. To study wound healing properties in rats, AC (100mg/mL, 200 microL/wound/day) was topically administered during 10 days and wound area was evaluated every day. Allantoin (100mg/mL, 200 microL/wound/day) was used as standard drug. After treatment, wound sites were removed for histopathological analysis and total collagen determination. RESULTS AC stimulated fibroblast growth in a concentration dependent way (EC50=30 microg/mL), increased in vitro collagen production and demonstrated moderate antioxidant capacity. In vivo, AC reduced wound size in 96%, whereas saline group showed only 36% wound healing. CONCLUSION AC efficiency seems to involve fibroblast growing stimulus and collagen synthesis both in vitro and in vivo, beyond moderate scavenging activity, corroborating Crajiru folk use.

Antioxidative and in vitro antiproliferative activity of Arctium lappa root extracts.

BackgroundArctium lappa, known as burdock, is widely used in popular medicine for hypertension, gout, hepatitis and other inflammatory disorders. Pharmacological studies indicated that burdock roots have hepatoprotective, anti-inflammatory, free radical scavenging and antiproliferative activities. The aim of this study was to evaluate total phenolic content, radical scavenging activity by DPPH and in vitro antiproliferative activity of different A. lappa root extracts.MethodsHot and room temperature dichloromethanic, ethanolic and aqueous extracts; hydroethanolic and total aqueous extract of A. lappa roots were investigated regarding radical scavenging activity by DPPH, total phenolic content by Folin-Ciocalteau method and antiproliferative in vitro activity was evaluated in human cancer cell lines. The hydroethanolic extract analyzed by high-resolution electrospray ionization mass spectroscopy.ResultsHigher radical scavenging activity was found for the hydroethanolic extract. The higher phenolic contents were found for the dichloromethane, obtained both by Soxhlet and maceration extraction and hydroethanolic extracts. The HRESI-MS demonstrated the presence of arctigenin, quercetin, chlorogenic acid and caffeic acid compounds, which were identified by comparison with previous data. The dichloromethane extracts were the only extracts that exhibited activity against cancer cell lines, especially for K562, MCF-7 and 786-0 cell lines.ConclusionsThe hydroethanolic extracts exhibited the strongest free radical scavenging activity, while the highest phenolic content was observed in Soxhlet extraction. Moreover, the dichloromethanic extracts showed selective antiproliferative activity against K562, MCF-7 and 786-0 human cancer cell lines.

Constituintes químicos de Luehea divaricata Mart. (Tiliaceae)

Chemical studies of the leaves of L. divaricata afforded 3b-p-hydroxybenzoyl-tormentic acid, a triterpene with an ursene-type skeleton, a mixture whose main compound was an oleanene derivative, the maslinic acid, a C-glycoside flavone, vitexin and glucopyranosylsitosterol. A flavonoid, characterized as (-)-epicatechin, which belongs to the flavan-3-ol class, was isolated from the stems bark. The structures of the compounds were elucidated by spectroscopic analysis. The antibacterial, antifungal and antiproliferative activities of the crude methanolic extracts of leaves and bark were evaluated and the antibacterial properties of the fractions of the barks were also investigated.

The flavonoid content and antiproliferative, hypoglycaemic, anti-inflammatory and free radical scavenging activities of Annona dioica St. Hill

BackgroundAnnona dioica St. Hill (Annonacaeae) is a Brazilian plant used in folk medicine for the treatment of several types of rheumatisms and diarrhoea. The focus of this work was to evaluate the in vitro antiproliferative and antioxidant activity and the in vivo hypoglycaemic and anti-inflammatory activity of A. dioica and identify the principal constituents of this plant.MethodsThe crude methanol extract (EAD) and hexane (HF), chloroform (CF), ethyl acetate (EAF) and hydromethanol fractions (HMF) were evaluated for free radical scavenging activity using the DPPH assay. The EAD and EAF were assayed for hypoglycaemic activity in rats. The EAD was tested in an antiproliferation assay and for anti-inflammatory effects in paw oedema, in addition to myeloperoxidase activity induced by carrageenan (Cg) in mice. The EAF was assayed using chromatographic methods.ResultsThe fractionation of the EAF through chromatographic methods identified derivatives of the flavonoids quercetin and kaempferol. Among all the tested fractions, the ethyl acetate and hydromethanol fractions were the most potent, exhibiting an IC50 of 8.53 and 10.57 μg/mL, respectively, which is comparable to that of the commercial antioxidant butylated hydroxytoluene (BHT). The oral administration of the EAD (100 mg/kg) and EAF (15 mg/kg) inhibited the increase of glucose levels, resulting in a hypoglycaemic effect. The EAD (30 to 300 mg/kg) exhibited an anti-oedematogenic effect in Cg-induced paw oedema in a time- and dose-dependent manner. The results showed a reduction of MPO activity by A. dioica 6 h after the induction of paw oedema at all doses tested with maximal inhibition at 300 mg/kg.ConclusionsOur results reveal for the first time that compounds contained in the A. dioica leaves exert anti-inflammatory, hypoglycaemic, antiproliferative, and antioxidant effects. The antioxidant activity may be associated with the presence of flavonoids.

Toxicity of artemisinin [Artemisia annua L.] in two different periods of pregnancy in Wistar rats

Artemisinin compounds are important for treating multidrug-resistant malaria; however, the possible resorption and abnormalities observed in animal reproduction studies may contraindicate artemisinin use during the first trimester. To evaluate whether artemisinin interferes with developmental outcomes at different periods of pregnancy, Wistar rats were treated by gavage with increasing doses of 7, 35 and 70 mg/kg/day from gestational day [GD] 7 to 13 or 14 to 20. Viable embryos and post-implantation losses, and progestagens and testosterone levels, were monitored in the former treatment group and pregnancy and outcomes data, post-implantation losses and male and female developmental endpoints of the offspring were evaluated in the latter treatment group. Results indicate toxicity for both periods of treatment, with lower sensitivity at later stages of pregnancy. The results showed that dosing with 35 or 75 mg/kg of artemisinin caused high percentages of post-implantation losses that correlated with a trend to lower maternal progestagens and a significant maternal testosterone decrease. These findings demonstrate that oral administration of artemisinin can adversely effect post-implantation development and pregnancy in the rat.

Cytotoxicity and antitumoral activity of dichloromethane extract and its fractions from Pothomorphe umbellata

The cytotoxicity of the dichloromethane crude extract (DCE), obtained from the aerial parts of Pothomorphe umbellata (L.) Miq (Piperaceae), was evaluated against nine human cancer cell lines (MCF-7, NCI-ADR/RES, OVCAR-3, PC-3, HT-29, NCI-H460, 786-O, UACC-62, K-562). The DCE presented antiproliferative activity with good potency against all cell lines at low concentrations (between 4.0 and 9.5 microg/mL) and with selectivity (1.55 microg/mL) for the leukemia cell line (K-652). DCE (100, 200, 300 and 400 mg/kg, ip) was also evaluated in the Ehrlich ascites tumor model. Both the survival number and the life span of the animals that died increased by at least 45 and 50%, respectively (8 animals per group), demonstrating P. umbellata extract potential anticancer activity. The results of the in vivo antitumor activity prompted the fractionation of the crude extract. The crude extract was submitted to dry column chromatography with dichloromethane-methanol (99:1). The column effluent fractions were extracted with methanol, dried under vacuum yielding fractions FR1 (less polar), FR2 (medium polarity), and FR3 (polar), which were analyzed for their growth inhibition or cytotoxic properties by a 48-h sulforhodamine B cell viability assay by measuring the total protein content. FR1 demonstrated high potency and cytotoxicity, a result compatible with the high toxicity of oxalic acid; FR2, containing 4-nerolidylcathecol, presented the lowest cytotoxic activity compared to the other two fractions but with selectivity for prostate cancer cell line; FR3, containing a mixture of steroids described in the literature as possessing various biological activities, also presented potent anticancer in vitro activity. These results suggest that P. umbellata DCE in vivo antitumor activity may be a consequence of the activity of different active principles.

Synthesis, antitumor and antimicrobial activity of novel 1-substituted phenyl-3-[3-alkylamino(methyl)-2-thioxo-1,3,4-oxadiazol-5-yl] β-carboline derivatives

Com o proposito de aumentar a atividade anticâncer demonstrada anteriormente pelas 1-fenilssubstituido-3-(2-tioxo-1,3,4-oxadiazol-5-il) b-carbolinas 1a-c, neste trabalho foram realizadas a sintese e a avaliacao in vitro da atividade antitumoral de novas bases de Mannich 2-7(a-c), derivadas da introducao de diferentes grupos alquilamino(metil) na unidade 1,3,4-oxadiazol de 1a-c. Os derivados 1a-c e 2-7(a-c) foram tambem avaliados quanto as atividades antibacteriana e antifungica. Adicionalmente, um estudo in silico das propriedades de ADME dos novos compostos sintetizados 2-7(a-c) foi realizado pela avaliacao de seus parâmetros de Lipinski e de dados de area de superficie topologica polar (TPSA) e de porcentagem de absorcao (% ABS). With the purpose of activity enhancement of 1-substituted phenyl-3-(2-thioxo-1,3,4-oxadiazol5-yl) b-carbolines 1a-c, reported as potential antitumor agents in our previous study, herein we report the synthesis and antitumor activity evaluation of several novel Mannich bases 2-7(a-c), by the introduction of different alkylamino(methyl) groups in the 1,3,4-oxadiazole unity of 1a-c. The antimicrobial activities of 1a-c and of 2-7(a-c) were also evaluated. Additionally, an in silico study of the ADME properties of novel synthesized b-carboline derivatives 2-7(a-c) was performed by evaluation of their Lipinski’s parameters and topological polar surface area (TPSA) and percentage of absorption (% ABS) data.