Cytotoxicity and anti-inflammatory effects of the extract, fractions and alkaloids from Palicourea minutiflora (Rubiaceae).

Palicourea species has been used in folk medicine in the treatment of some diseases including cancer and inflammatory disorders. This work aimed to evaluate the in vitro antiproliferative and in vivo topical anti-inflammatory activities of the methanolic extract, fractions and two major alkaloids isolated from Palicourea minutiflora. Methanolic extract, non-alkaloidal and alkaloidal fractions exhibited strong growth inhibition for ovarian cell lines (OVCAR-3, GI50 = 3.8 at 16.3 µg mL-1) and the vincosamide alkaloid revealed selective effect on the growth of glioma cell lines (U251, GI50 = 33.0 µg mL-1) compared with doxorubicin (DOX, GI50 = 0.42 and 0.025 µg mL-1, respectively) anticancer drug. Methanolic extract, fractions and strictosidinic acid showed significant inhibitory effect with 62.7% at 77.5% (p < 0.05) to ear edema induced by croton oil and 81% at 100% (p < 0.05) to myeloperoxidase assay compared with indomethacin (positive control) 68.4% and 91.3% (p < 0.05), respectively.

Antiproliferative activity and chemical constituents of Lonchocarpus cultratus (Fabaceae).

The aerial parts of L. cultratus were submitted to a phytopharmacological investigation in order to isolate and identify the major secondary metabolites and evaluate its crude extract, fractions and isolated compounds for antiproliferative activity. Seven compounds were isolated and identified as the chalcones 2',4'-dihydroxy-5'-prenylchalcone (1) and isocordoin (2), the flavanone 8-prenylpinocembrin (3), the alkaloid 4-hydroxy-N-methylproline (4), the triterpenes lupeol and lupenone. These compounds were identified by nuclear magnetic resonance of 1H and 13C data in comparison with literature. Hexanic fraction and chalcone 2',4'-dihydroxy-5'-prenylchalcone showed potent results against human cancer cell lines tested.

Structural Characterization and Biological Evaluation of 18-Nor-ent-labdane Diterpenoids from Grazielia gaudichaudeana.

The phytochemical investigation of Grazielia gaudichaudeana aerial parts yielded 15 compounds, including diterpenes, triterpenes, sterols and flavonoids. With exception to ent-kaurenoic acid diterpenes, the compounds isolated are being described for the first time in this species. Some unusual 1 H-NMR chemical shifts of 18-nor-ent-labdane (7-9) led us carry out a conformational analysis by theoretical calculations in order to support the experimental data. Moreover, due to the limitation of studies focused on pharmacological potential of Grazielia gaudichaudeana, the present study was carried out to investigate the antioxidant, antiproliferative, antiviral, antileishmanial and antimicrobial activities from the extract, fractions and isolated compounds obtained from this species. Ethyl acetate fraction showed significant activity in the antiproliferative assay, with GI50 range of 3.9 to 27.2 µg mL-1 . Dichloromethane fraction, rich in diterpenoids, inhibited all human tumor cell lines tested, and the nor-labdane 7 showed potent cytotoxic activity against glioma and ovary cancer cell lines.

Antitumoral and Anticholinesterasic Activities of the Seven Species from Rubiaceae.

BACKGROUND: The genus Psychotria and Palicourea are reported as a source of alkaloids and iridoids, which exhibit biological activities. This study aimed to evaluate antiproliferative and anticholinesterase activities and quantification of the alkaloids of seven species among the genus found in Mato Grosso do Sul region in Brazil. METHODS: Concentrations of alkaloids were measured spectrophotometrically. The extracts were submitted to antiproliferative activity against ten cell lines. The anticholinesterase activity of the extracts was developed using brain structures of male Wistar rats: cerebral cortex, hippocampus, hypothalamus and striatum by the Ellman method. RESULTS: Alkaloids from Psychotria and Palicourea species were quantified which showed values of 47.6 to 21.9 µg/g. Regarding the antiproliferative potential, Palicourea crocea demonstrated selectivity against the 786-0 cell line (GI50: 22.87 µg/mL). Psychotria leiocarpa inhibited cell growth against OVCAR-3 (GI50: 3.28 µg/mL), K-562 (GI50: 5.26 µg/mL), HaCaT (GI50: 27.20 µg/mL), PC-3 (GI50: 34.92 µg/mL), MCF-7 (GI50: 35.80 µg/mL) and P. capillacea showed activity against OVCAR-3 (GI50: 2.33 µg/ml) and U251 (GI50: 16.66 µg/ml). The effect of acetylcholinesterase inhibition was more effective in the hippocampus, demonstrating inhibition for Paliourea crocea, Psychotria deflexa, P. brachybotrya and P. leiocarpa of 70%, 57%, 50% and 40%, respectively, followed by P. poeppigiana and P. capillacea, inhibiting 21%, compared to the control. CONCLUSION: Herein, the present work showed for the first time, anticholinesterasic and antiproliferative activities of extracts of Palicourea and Psychotria seem to be mainly associated with the levels of alkaloids in the leaves of these species.

Anti-inflammatory, Antioxidant and Antiproliferative Activities from Trichilia silvatica (C.DC).

BACKGROUND: Trichilia silvatica, popularly known as "catiguá-branco", is distributed in Brazil (Mato Grosso do Sul), and members of this genus are commonly used for the treatment of rheumatism (arthritis). The aim of this research was to investigate the anti-inflammatory, antioxidant and antiproliferative activities of the methanolic extract of the leaves (MEL-TS) and bark (MEB-TS) of T. silvatica. We also evaluated the concentration of phenolic compounds, flavonoids, flavonol, and condensed tannins by liquid chromatography - photodiode array (LC/PDA) analysis. METHODS: The MEL-TS and MEB-TS revealed the presence of caffeic acid in both extracts by LC/PDA. The samples were evaluated for antioxidant activity using free-radical scavenging and lipoperoxidation assays. The anti-inflammatory effects were studied in carrageenan-induced paw edema, pleurisy and zymosan-induced arthritis. RESULTS: The MEL-TS and MEB-TS showed the total phenolic concentration (270.8 ± 17.10 mg gallic acid equivalents GAE/g extract and 278.8 ± 25.13 mg GAE/ g extract, respectively), and flavonoids in MEL-TS (209.30 ± 2.91 mg quercetin equivalents QE/ g extract). In the lipoperoxidation assay, exhibited moderate antioxidant activity with IC50 values ≤ 35.32 µg/mL. Both extracts inhibited oedema induced by carrageenan at 2 h and 4 h, inhibited leukocyte migration at 6 h post administration, and did not impact zymosan-induced arthritis. Finally, MEL-TS was particularly effective against prostate cell line (GI50 ≤ 0.22 µg/mL). CONCLUSION: Overall, the results indicated that T. silvatica reduce migration leukocytes activity, edema formation in these models of experimental arthritis could explain the popular use for treatment of inflammatory processes (rheumatism).

Antioxidative, Antiproliferative and Antimicrobial Activities of Phenolic Compounds from Three Myrcia Species.

Myrcia bella Cambess., Myrcia fallax (Rich.) DC. and Myrcia guianensis (Aubl.) DC. (Myrtaceae) are trees found in Brazilian Cerrado. They have been widely used in folk medicine for the treatment of gastrointestinal disorders, hemorrhagic and infectious diseases. Few reports have been found in the literature connecting their phenolic composition and biological activities. In this regard, we have profiled the main phenolic constituents of Myrcia spp. leaves extracts by ESI(−)Q-TOF-MS. The main constituents found were ellagic acid (M. bella), galloyl glucose isomers (M. guianensis) and hexahydroxydiphenic (HHDP) acid derivatives (M. fallax). In addition, quercetin and myricetin derivatives were also found in all Myrcia spp. extracts. The most promising antioxidant activity, measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity, was found for M. fallax extracts (EC50 8.61 ± 0.22 µg·mL−1), being slightly less active than quercetin and gallic acid (EC50 2.96 ± 0.17 and 2.03 ± 0.02 µg·mL−1, respectively). For in vitro antiproliferative activity, M. guianensis showed good activity against leukemia (K562 TGI = 7.45 µg·mL−1). The best antimicrobial activity was observed for M. bella and M. fallax to Escherichia coli (300 and 250 µg·mL−1, respectively). In conclusion, the activities found are closely related to the phenolic composition of these plants.

Anti-inflammatory and antiproliferative activities of Ixora brevifolia Benth. (Rubiaceae).

The crude extract and fractions from the branches of Ixora brevifolia, a tree found in the Brazilian Cerrado, were tested for anti-inflammatory and in vitro antiproliferative effects. The crude extract and n-hexane fraction exhibited significant inhibition of ear oedema in mice, while n-hexane-precipitated and chloroform fractions strongly inhibited the myeloperoxidase activity in ear tissue. The n-hexane and n-hexane-precipitated fractions showed strong growth inhibition for glioma cell line and the hydromethanolic fraction inhibited the growth of leukaemia cell line.

Derivatives of furanditerpenes from Pterodon genus: Pharmacological studies disclose their potential as chronic pain relief in mice.

Pterodon genus fruits are commercially available at the Brazilian medicinal market used in folk medicine due to their anti-inflammatory, analgesic, and anti-rheumatic effects. Previous studies demonstrated that furanditerpenes possessing vouacapan skeleton, isolated from Pterodon genus, possess expressive antinociceptive activities, with promising moiety for the development of new analgesic products. The antinociceptive properties of compounds 6α,7ß-6α-hidroxivouacapan-7ß-17ß-lactone (HVL) and 6α-oxovouacapan-7ß-17ß-lactone (OVL), semi-synthetic analogues of furanditerpenes previously reported as analgesic agents were evaluated on animal experimental models (Spindola et al., 2010, 2011). The chemical-induced pain methods used in the present work, demonstrated for the first time that both compounds HVL and OVL have potential as important templates for the development of chronic pain control drugs. The main findings of this work were that both compounds were: effective in the writhing test; reduced paw edema in the carrageenan test; effective in the inflammatory phase of the formalin test corroborating their activity against inflammatory pain conditions; effective on reducing pain through the stimulation of vanilloid receptors sensible to capsaicin (an important pathway for chronic pain maintenance); reduced the pain stimulus caused by PGE2 injection (a pathway involved in chronic pain hypersensitivity); effective on decreasing mechanical allodynia in the CFA-model, demonstrating their potential use against chronic pain disorders.

Cytotoxic activity of Guettarda pohliana Müll. Arg. (Rubiaceae).

The cytotoxic activity of crude extracts and their fractions from leaves and roots of G. pohliana was assessed against nine human cancer cell lines: melanoma (UACC-62), breast (MCF-7), breast expressing the multidrug resistance phenotype (NCI-ADR), lung (NCI-460), prostate (PCO-3), kidney (786-0), ovarian (OVCAR), colon (HT-29) and leukaemia (K-562). The hexane fraction from leaves (HL) and ethyl acetate (EAR), chloroform (CR) and hydromethanolic (HMR) fractions from roots were the most active fractions against K-562 with GI50 values being lower than 1 µg mL⁻¹. Also, CR and HMR fractions were active against UACC-62 cell line in the same order of magnitude. The phytochemical study of the CR fraction allowed identifying the known iridoids secoxyloganin, sweroside and loganin.

Antiproliferative activity of Luehea candicans Mart. et Zucc. (Tiliaceae).

Luehea candicans Mart. et Zucc. (Tiliaceae) is known as 'açoita-cavalo' and is one of the most important medicinal plants found in the Brazilian cerrado. The crude methanolic extracts of the branches and leaves and their fractions were evaluated using the following cancer cell lines: MCF-7 (breast), NCI-ADR (breast expressing the multidrug resistance phenotype), NCI-460 (lung), UACC-62 (melanoma), 786-0 (kidney), OVCAR (ovarian), PCO-3 (prostate), HT-29 (colon) and K-562 (leukaemia). The crude methanolic extracts from the branches (B) and leaves (L) were able to inhibit the growth of the K-562 and 786-0 cell lines in a dose-dependent manner, with GI(50) values of 8.1 and 5.4 µg mL(-1), respectively. The hexane (L1), chloroform (L2) and methanol (L4) fractions derived from extract L showed a high selectivity and pronounced cytostatic activity against 786-0 (GI(50) ~ 40 µg mL(-1)). A significant amount of lupeol was isolated from fraction L2. The chloroform (B2) and methanol (B3) fractions derived from extract (B) exhibited less selectivity, showing the highest cytostatic activity against K-562, NCI-ADR, OVCAR, MCF-7 and NCI-460 cells, with GI(50) values between 27 and 40 µg mL(-1). Lupeol, betulin, a mixture of steroids, (-)-epicatechin, vitexin and liriodendrin were isolated from these active fractions.

Antineoplastic 31-norcycloartanones from Solanum cernuum vell.

Triterpenoids with 31-norcycloartanone structure were isolated for the first time from the Solanum genus. Cycloeucalenone and 24-oxo-31-norcycloartanone were the main constituents of the dichloromethane extract of Solanum cernuum Vell. leaves [7% (w/w) and 1.47% (w/w)]. Both triterpenoids were tested against human tumour cell lines, and 24-oxo-31-norcycloartanone was significantly active and selective against the lung tumour cell line NCI-H460 with total growth inhibition at 1.10 microg/mL, growth inhibition 50 at 0.19 microg/mL and lethal concentration 50 at 8.43 microg/mL, while cycloeucalenone showed poor activity. A homologous series of alkanes (C25-C34), beta-sitosterol, and the xanthophyll lutein were also identified. The antiulcer activity was assayed for the dichloromethane extract. In the gastric ulcer model induced by 95% ethanol, administration of 500, 1000 and 2000 mg/kg/po dichloromethane extract gave ulcer lesion indices of, respectively, 38.2, 61.0 and 81.9%, while carbenoxolone inhibited 88.9% at 200 mg/kg. In the gastric ulcer model induced by indomethacin the dichloromethane extract showed a small percentage of lesion inhibition. The ethanol extract was also analyzed and was mainly composed of glycoalkaloids, peptides and disaccharides.