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Background: The genus Uncaria (Rubiaceae) has several biological properties significant to human health. However, the mechanisms underlying the protective effect of this plant on bone diseases are uncertain., Purpose: The present study investigated the role of Uncaria tomentosa extract (UTE) on alveolar bone loss in rats and on osteoclastogenesis in vitro., Materials: UTE was characterized by an Acquity UPLC (Waters) system, coupled to an Electrospray Ionization (ESI) interface and Quadrupole/Flight Time (QTOF, Waters) Mass Spectrometry system (MS). The effect of UTE treatment for 11 days on the ligature-induced bone loss was assessed focusing on several aspects: macroscopic and histological analysis of bone loss, neutrophil and osteoclast infiltration, and anabolic effect. The effect of UTE on bone marrow cell differentiation to osteoclasts was assessed in vitro., Results: The analysis of UTE by UPLC-ESI-QTOF-MS/MS identified 24 compounds, among pentacyclic or tetracyclic oxindole alkaloids and phenols. The administration of UTE for 11 days on ligature-induced rat attenuated the periodontal attachment loss and alveolar bone resorption. It also diminished neutrophil migration to the gingiva tissue, demonstrated by a lower level of MPO. UTE treatment also decreased the level of RANKL/OPG ratio, the main osteoclast differentiation-related genes, followed by reduced TRAP-positive cell number lining the alveolar bone. Additionally, the level of bone-specific alkaline phosphatase, an anabolic bone marker, was elevated in the plasma of UTE treated rats. Next, we determined a possible direct effect of UTE on osteoclast differentiation in vitro. The incubation of primary osteoclast with UTE decreased RANKL-induced osteoclast differentiation without affecting cell viability. This effect was supported by downregulation of the nuclear factor activated T-cells, cytoplasmic 1 expression, a master regulator of osteoclast differentiation, and other osteoclast-specific activity markers, such as cathepsin K and TRAP., Conclusion: UTE exhibited an effective anti-resorptive and anabolic effects, which highlight it as a potential natural product for the treatment of certain osteolytic diseases, such as periodontitis., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Ethnopharmacological Relevance: Casearia sylvestris is a medicinal plant traditionally used to treat snakebites, wounds, inflammation and gastric ulcers and scientific supports for have demonstrated its antitumor, antihyperlipidemic and antiparasitic properties., Aim of the Study: To assess the effects of a fraction with casearins (FC) on adult mice using classical experimental models of animal behavior and theoretical calculations to verify the interaction of Casearin X (Cas X) with neuron receptors., Materials and Methods: Animals divided in 6 groups (n=9/group) were intraperitoneally treated with vehicle (DMSO 4%), FC (2.5, 5, 10 and 25mg/kg/day) and diazepam (2mg/kg) for 7 days. Thirty minutes after the last dose of treatment, acute toxicity and behavioral experiments were performed., Results: The highest dose of FC (25mg/kg/day) caused diarrhea, weight loss and death of one animal. Elevated plus maze test showed that lower doses [2.5mg/kg/day (36.4±5.1s) and 5mg/kg/day (43.9±6.2s)] increased the time spent in open arms (TSOA). Open field test revealed reduction in the number of crossings (54.9%, 51.1%, 48% and 67.7% for 2.5, 5, 10 and 25mg/kg/day, respectively) in all doses of FC studied and decrease of rearings at 25mg/kg/day (p<0.05). Computational calculations showed that the inhibition constant (Ki) for the Cas X-D 1 complex is up to 1000-fold more favourable than the Cas X-GABA A complex. All ∆G° values obtained for Cas X-D 1 complexes were more negative than those seen with Cas X-GABA A complexes., Conclusions: Findings indicate a probable anxiolytic action of the FC since it reduces the number of crossings and rearings and prolonged the time spent in open arms, without sedative and myorelaxant effects, probably due to the interaction of Cas X with dopaminergic system., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Remirea maritima has been widely used in the treatment of diarrhea, kidney disease, and high fever and for therapeutic purposes, such as an analgesic and anti-inflammatory. However, few scientific research studies on its medicinal properties have been reported., Purpose: The present study aimed to investigate the anticancer potential of aqueous extract (AE), 40% hydroalcoholic extracts (40HA) and 70% (70HA) from R. maritima in experimental models and to identify its phytochemical compounds., Methods: The chemical composition of AE, 40HA and 70HA was assessed by HPLC-DAD and ESI-IT-MS/MS. In vitro activity was determined on cultured tumor cell, NCI-H385N (Broncho-alveolar carcinoma), OVCAR-8 (Ovarian carcinoma) and PC-3M (prostate carcinoma) by the MTT assay, and the in vivo antitumor activity was assessed in Sarcoma 180-bearing mice. Toxicological parameters were also evaluated as well as the humoral immune response., Results: Among the aqueous and hydroalcoholic extracts of R. maritima, only 40HA showed in vitro biological effect potential, presenting IC50 values of 27.08, 46.62 and >50µg/ml for OVCAR-8, NCI-H385M and PC-3M cells lines, respectively. Regarding chemical composition, a mixture of isovitexin-2''-O-β-D-glucopyranoside, vitexin-2''-O-β-D-glucopyranoside, luteolin-7-O-glucuronide and 1-O-(E)-caffeoyl-β-D-glucose were identified as the major phytochemical compounds of the extracts. In the in vivo study, the tumor inhibition rates were 57.16-62.57% at doses of 25mg/kg and 50mg/kg, respectively, and the tumor morphology presented increasing numbers of apoptotic cells. Additionally, 40HA also demonstrated significantly increased of OVA-specific total Ig., Conclusions: 40HA exhibited in vitro and in vivo anticancer properties without substantial toxicity that could be associated with its immunostimulating properties., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

Ethnopharmacological Relevance: Casearia sylvestris (Salicaceae) is found in South America and presents antiulcerogenic, cytotoxic, antimicrobial, anti-inflammatory and antihypertensive activities., Aim of the Study: To assess the in vivo and ex vivo antitumor action of a fraction with casearins (FC) and its main component - Casearin X-isolated from C. sylvestris leaves., Materials and Methods: Firstly, Sarcoma 180 bearing Swiss mice were treated with FC and Cas X for 7 days. Secondly, BALB/c nude animals received hollow fibers with colon carcinoma (HCT-116) or glioblastoma (SF-295) cells and were treated with FC for 4 days. On 5th day, proliferation was determined by MTT assay., Results: FC 10 and 25mg/kg/day i.p. and 50mg/kg/day oral and Cas X 25mg/kg/day i.p. and 50mg/kg/day oral revealed tumor growth inhibition rates of 35.8, 86.2, 53.7, 90.0 and 65.5% and such tumors demonstrated rare mitoses and coagulation necrosis areas. Similarly, FC reduced multiplying of HCT-116 and SF-295 cells when evaluated by the Hollow Fiber Assay (2.5 and 5mg/kg/day i.p. and 25 and 50mg/kg/day oral), with cell growth inhibition rates ranging from 33.3 to 67.4% (p<0.05). Flow cytometry experiments revealed that FC reduced membrane integrity and induced DNA fragmentation and mitochondrial depolarization (p<0.05)., Conclusions: FC and Cas X were efficient antitumor substances against murine and human cancer cells and caused reversible morphological changes in liver, kidneys and spleens, emphasizing clerodane diterpenes as an emerging class of anticancer molecules., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Plants are promising sources of new bioactive compounds. The aim of this study was to investigate the cytotoxic potential of nine plants found in Brazil. The species studied were: Annona pickelii Diels (Annonaceae), Annona salzmannii A. DC. (Annonaceae), Guatteria blepharophylla Mart. (Annonaceae), Guatteria hispida (R. E. Fr.) Erkens & Maas (Annonaceae), Hancornia speciosa Gomes (Apocynaceae), Jatropha curcas L. (Euphorbiaceae), Kielmeyera rugosa Choisy (Clusiaceae), Lippia gracilis Schauer (Verbenaceae), and Hyptis calida Mart. Ex Benth (Lamiaceae). Different types of extractions from several parts of plants resulted in 43 extracts. Their cytotoxicity was tested against HCT-8 (colon carcinoma), MDA-MB-435 (melanoma), SF-295 (glioblastoma), and HL-60 (promielocitic leukemia) human tumor cell lines, using the thiazolyl blue test (MTT) assay. The active extracts were those obtained from G. blepharophylla, G. hispida, J. curcas, K. rugosa, and L. gracilis. In addition, seven compounds isolated from the active extracts were tested; among them, β-pinene found in G. hispida and one coumarin isolated from K. rugora showed weak cytotoxic activity. In summary, this manuscript contributes to the understanding of the potentialities of Brazilian plants as sources of new anticancer drugs., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: The aim of this study was to evaluate the efficacy of Mentha crispa in the treatment of women with Trichomonas vaginalis infection (TVI)., Methods: This was a randomized, double-blind, and controlled clinical trial consisting of three phases, pre-treatment, treatment, and post-treatment. Sixty female patients were randomized to a treatment group, M. crispa (24 mg) or secnidazole (2,000 mg), both consisting of single dose., Results: After treatment the proportion of patients without TVI in secnidazole group was 96.6% and in the M. crispa group was 90%, no difference was found between groups (P = 0.6120). We observed improvement in vaginal discharge, malodorous vaginal secretion, dyspareunia, dysuria, pelvic pain, and burning and itching in the genital area in patients of both groups of treatment, with no statistically significant differences between them (P > 0.05). Adverse effects were significantly higher (P = 0.0006) in the secnidazole group (66.6%) than in the M. crispa group (20%), that being mostly nausea and metallic taste with statistically significant differences between treatment groups (P < 0.001)., Conclusion: This study is the first to show that M. crispa is effective and safe, representing an alternative for the treatment of TVI in women.

Purpose: To determine the effects of green propolis extracted in L-lysine (WSDP) and of L- lysine for 40 weeks on induced rat bladder carcinogenesis., Methods: The animals (groups I, II, III, IV, V and VI) received BBN during 14 weeks. Group I was treated with propolis 30 days prior received BBN, and then these animals were treated daily with propolis; Groups II and III was treated with subcutaneous and oral propolis (respectively) concurrently with BBN. The animals of Group IV were treated L-lysine; Group V received water subcutaneous; and Group VI received only to BBN. Among the animals not submitted to carcinogenesis induction, Group VII received propolis, Group VIII received L-lysine and Group IX received water., Results: The carcinoma incidence in Group I was lower than that of control (Group VI). The carcinoma multiplicity in Group IV was greater than in Group VI. All animals treated with L-lysine developed carcinomas, and they were also more invasive in Group IV than in controls. On the other hand, Group VIII showed no bladder lesions., Conclusion: The WSDP is chemopreventive against rat bladder carcinogenesis, if administered 30 days prior to BBN , and that L-lysine causes promotion of bladder carcinogenesis.

Folk uses and scientific investigations have highlighted the importance of Casearia sylvestris extracts and their relevant bioactive potential. The aim of this work was to review the pharmacological properties of C. sylvestris, emphasizing its anti-ulcer, anti-inflammatory, anti-ophidian and antitumor potentialities. Ethanolic extracts and essential oil of their leaves have antiulcerogenic activity and reduce gastric volume without altering the stomach pH, which corroborates their consumption on gastrointestinal disorders. Leaf water extracts show phospholipase A(2) inhibitory activity that prevents damage effects on the muscular tissue after toxin inoculation. This antiphospholipasic action is probably related to the use as an anti-inflammatory, proposing a pharmacological blockage similar to that obtained with non-steroidal anti-inflammatory drugs on arachidonic acid and cyclooxygenase pathways. Bioguided-assay fractionations lead to the identification of secondary metabolites, especially the clerodane diterpenes casearins (A-X) and casearvestrins (A-C), compounds with a remarkable cytotoxic and antitumor action. Therefore, the C. sylvestris shrub holds a known worldwide pharmacological arsenal by its extensive folk utilization, exciting searches for new molecules and a better comprehension about biological properties.

This study assessed the antiproliferative and cytotoxic potential against tumor lines of ethanolic seed extracts of 21 plant species belonging to different families from Northeastern Brazil. In addition, some underlying mechanisms involved in this cytotoxicity were also investigated. Among the 21 extracts tested, the MTT assay after 72 h of incubation demonstrated that only the ethanolic extract obtained from Myracrodruon urundeuva seeds (EEMUS), which has steroids, alkaloids and phenols, showed in vitro cytotoxic activity against human cancer cells, being 2-fold more active on leukemia HL-60 line [IC(50) value of 12.5 (9.5-16.7) μg/mL] than on glioblastoma SF-295 [IC(50) of 25.1 (17.3-36.3) μg/mL] and Sarcoma 180 cells [IC(50) of 38.1 (33.5-43.4) μg/mL]. After 72h exposure, flow cytometric and morphological analyses of HL-60-treated cells showed that EEMUS caused decrease in cell number, volume and viability as well as internucleosomal DNA fragmentation in a dose-dependent way, suggesting that the EEMUS triggers apoptotic pathways of cell death.

Background: Laxatives are much utilized, but few clinical trials assessed the efficacy of phytotherapics in the functional constipation., Aim: The aim of this study was to evaluate the efficacy of the tincture of jalapa in the treatment of patients with functional constipation., Methods: Double-blind, randomized, placebo-controlled clinical trial was used in this study. Seventy-six patients were assigned to two treatment groups, jalapa or placebo. The study consisted of three phases: pre-treatment, treatment, and post-treatment, each phase lasting 7 days. The mean frequency of stools, the mean consistency of stools, and the presence of pain and effort to evacuate were assessed. We monitored adverse events before, during, and after the administration of 15 mL of tincture of jalapa or placebo., Results: After treatment, the mean frequency of stools of the jalapa group (0.58 ± 0.25 stools/day; P < 0.0001) was higher than in the placebo group (0.36 ± 0.20 stools/day). In the pre-treatment, stool consistency, according to the Bristol scale, ranged from types 1 to 3 for both groups. The jalapa group showed improved mean consistency of stools (P = 0.0102) after treatment, approximately ranging between types 2 and 4, while the placebo group did not show statistically significant differences (P = 0.1446). The reduction of pain (P = 0.0061) and effort (P = 0.0289) in the jalapa group were statistically significant. Both treatments were well tolerated by the patients., Conclusion: The tincture of jalapa was shown to be effective in the acute treatment of functional constipation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Kaurane diterpenes are considered important compounds in the development of new highly effective anticancer chemotherapeutic agents. Genotoxic effects of anticancer drugs in non-tumour cells are of special significance due to the possibility that they induce secondary tumours in cancer patients. In this context, we evaluated the genotoxic and mutagenic potential of the natural diterpenoid kaurenoic acid (KA), i.e. (-)-kaur-16-en-19-oic acid, isolated from Xylopia sericeae St. Hill, using several standard in vitro and in vivo protocols (comet, chromosomal aberration, micronucleus and Saccharomyces cerevisiae assays). Also, an analysis of structure-activity relationships was performed with two natural diterpenoid compounds, 14-hydroxy-kaurane (1) and xylopic acid (2), isolated from X. sericeae, and three semi-synthetic derivatives of KA (3-5). In addition, considering the importance of the exocyclic double bond (C16) moiety as an active pharmacophore of KA cytotoxicity, we also evaluated the hydrogenated derivative of KA, (-)-kauran-19-oic acid (KAH), to determine the role of the exocyclic bond (C16) in the genotoxic activity of KA. In summary, the present study shows that KA is genotoxic and mutagenic in human peripheral blood leukocytes (PBLs), yeast (S. cerevisiae) and mice (bone marrow, liver and kidney) probably due to the generation of DNA double-strand breaks (DSB) and/or inhibition of topoisomerase I. Unlike KA, compounds 1-5 and KAH are completely devoid of genotoxic and mutagenic effects under the experimental conditions used in this study, suggesting that the exocyclic double bond (C16) moiety may be the active pharmacophore of the genetic toxicity of KA., (2010 Elsevier B.V. All rights reserved.)

The cytotoxic potential of stem organic extracts from Calotropis procera (Asclepiadaceae) was firstly evaluated against cancer cell lines by MTT assay. Subsequently, samples considered cytotoxic were tested for antimitotic activity on sea urchin egg development and for in vivo antiproliferative activity in mice bearing Sarcoma 180 tumor. Among the five extracts (hexane, dichloromethane, ethyl acetate, acetone and methanol), ethyl acetate and acetone extracts displayed higher cytotoxic potential against tumor cells, with IC50 ranging from 0.8 to 4.4 microg/mL, while methanolic extract was weakly cytotoxic. Cytotoxic extracts also exhibited cell division inhibition capacity by antimitotic assay, revealing IC50 values lower than 5 microg/mL. In the in vivo antitumor assessments, ethyl acetate- and acetone-treated animals showed tumor growth inhibition ratios of 64.3 and 53.1%, respectively, with reversible toxic effects on liver and kidneys. Further studies are in progress in order to identify C. procera cytotoxic compound(s) and to understand the mechanism of action responsible for this tumor-decreasing potential.

Native and exotic Brazilian plants collected in the State of Minas Gerais were evaluated for their anticancer potential. Methanol extracts from leaves of 51 plant species were tested for cytotoxicity against four tumor cell lines: B16 (murine skin), HL-60 (human leukemia), MCF-7 (human breast), and HCT-8 (human colon). Plant extracts that exhibited IC(50) values less than 30 microg/ml against any tumor cell line were tested on sea urchin egg development and mouse erythrocytes. In addition, all extracts were evaluated for their general toxicity using the brine shrimp lethality assay. The most active extracts against the tumor cells were those obtained from Lantana fucata, Copaifera langsdorffii, and Momordica charantia. These three extracts inhibited sea urchin development from the first cleavage, but those from C. langsdorffii and M. charantia were very active against mouse erythrocytes. Only the L. fucata extract presented no hemolytic activity. Consequently, although the extracts of L. fucata, M. charantia, and C. langsdorffii could be useful in the development of new anticancer products, the first of these extracts is the most promising since it did not present unspecific toxicity, as suggested by negative results obtained with brine shrimp lethality and mouse erythrocytes assays.

Objectives: Alpinia zerumbet, known in Brazil as colônia, is popularly used as a diuretic, antihypertensive, anti-ulcerogenic and sedative. Based on this, we have investigated the central effects of the essential oil isolated from A. zerumbet leaves., Methods: Mice were treated once with 50 or 100 mg/kg of the essential oil, intraperitoneally, 30 min before being submitted to behavioural models of: locomotor activity (open-field), catalepsy, anxiety (elevated plus maze), depression (forced swimming test and tail suspension tests) as well as apomorphine-induced stereotypy., Key Findings: Results showed a dose-related decrease on locomotor activity and apomorphine-induced stereotypy. There was a decrease to the order of 55% of the grooming behaviour with both doses studied. The essential oil 100 mg/kg increased cataleptic activity (167%) and the immobility time in the forced swimming and tail suspension tests. Pretreatment with haloperidol (0.2 mg/kg, i.p.) alone also decreased locomotion, increased cataleptic activity and immobility time in the tail suspension test. No alterations in the elevated plus maze test were registered., Conclusions: The essential oil of A. zerumbet leaves had depressant and possible antipsychotic activity, since it could reverse the stereotypy induced by apomorphine, presenting effects comparable with those obtained with haloperidol treatment.

Unlabelled: The search for new anti-cancer drugs is one of the most prominent research areas of natural products. Numerous active compounds isolated from Brazilian Cerrado plant species have been studied with promising results., Aim of the Study: To investigate the cytotoxic potential of 412 extracts from Brazilian Cerrado plants used in traditional medicine belonging to 21 families against tumor cell lines in culture., Material and Method: Maceration of 50 plant species resulted in 412 hexane, dichloromethane, ethanol and hydroalcohol extracts. The cytotoxicity of the extracts was tested against human colon carcinoma (HCT-8), melanoma (MDA-MB-435), and brain (SF-295) tumor cell lines, using the thiazolyl blue test (MTT) assay. Bioassay-guided fractionation was performed for one active extract., Results and Conclusions: Twenty-eight of the 412 tested extracts demonstrated a substantial antiproliferative effect, at least 85% inhibition of cell proliferation at 50 microg/mL against one or more cell lines. Those extracts are obtained from different parts of Anacardiaceae, Annonaceae, Apocynaceae, Clusiaceae, Flacourtiaceae, Sapindaceae, Sapotaceae, Simaroubaceae and Zingiberaceae. Complete dose-response curves were generated and IC(50) values were calculated for these active extracts against four cell lines HCT-8, MDA-MB-435, SF-295 and HL-60 (leukemia), and their direct cytotoxic effects were determined. In summary, 14 extracts of 13 species showed toxicity in all tested tumor cell lines, with IC(50) values ranging from 0.1 to 19.1 microg/mL. The strongest cytotoxic activity was found for the hexane extract of Casearia sylvestris var. lingua stem bark, with an IC(50) of 0.1 microg/mL for HCT-8, 0.9 microg/mL for SF-295, 1.2 microg/mL for MDA-MB-435, and 1.3 microg/mL for HL-60, and Simarouba versicolor root bark, with an IC(50) of 0.5 microg/mL for HCT-8, 0.7 microg/mL for SF-295, 1.5 microg/mL for MDA-MB-435, 1.1 microg/mL for HL-60. Bioassay-guided fractionation of the last extract led to the isolation of glaucarubinone, which showed pronounced activity against the four cell lines studied. Further studies of the active extracts are necessary for chemical characterization of the active compounds and more extensive biological evaluations.

4-Nerolidylcatechol (1) was isolated from cultivated Pothomorphe peltata root on a multigram scale using straight-forward solvent extraction-column chromatography. New semi-synthetic derivatives of 1 were prepared and tested in vitro against multidrug-resistant Plasmodium falciparum K1 strain. Mono-O-methyl, mono-O-benzyl, O,O-dibenzyl and O,O-dibenzoyl derivatives 2-8 exhibited IC(50) in the 0.67-22.52 microM range. Mono-O-methyl ethers 6 and 7 inhibited the in vitro growth of human tumor cell lines HCT-8 (colon carcinoma), SF-295 (central nervous system), LH-60 (human myeloblastic leukemia) and MDA/MB-435 (melanoma). In general, derivatives 2-8 are more stable to light, air and pH at ambient temperatures than their labile, natural precursor 1. These derivatives provide leads for the development of a novel class of antimalarial drugs with enhanced chemical and pharmacological properties.

Seselin an angular pyranocoumarin at dose of 0.5, 4.5 or 40.5 mg/kg inhibited the writhing response induced by acetic acid in a significant and dose-dependent manner, by 19.5%, 26.2% and 41.4%, respectively. Using the same doses, seselin elicited a significant inhibition of formalin response during the second phase (inflammatory), by 90.3%, 97.8% and 95.3%, respectively. Besides, a significant reduction of licking time was observed during the first phase (neurogenic) at the highest doses of seselin, by 34.4% and 66.9%, respectively. On the contrary, in the hot plate test no effect was observed after seselin treatment. In conclusion, seselin was able to inhibit inflammatory hyperalgesia, suggesting that this natural product possesses both important peripheral anti-inflammatory and antinociceptive properties.

This study evaluates the potential neuroprotective properties of amburoside A, a glucoside isolated from Amburana cearensis, on rat mesencephalic cell cultures exposure to the neurotoxin 6-hydroxydopamine (6-OHDA). The parameters determined were cell viability by the 3[4,5-dimethylthiazole-2-il]-2,5-diphenyltetrazolium bromide (MTT) method, nitric oxide (NO) and free radical formation by the measurement of nitrite concentration and thiobarbituric acid reacting substance (TBARS) formation as an indication of cellular lipid peroxidation. The results showed that AMB was less effective as a curative agent in the MTT assay, since its addition after 6-OHDA did not reverse the neurotoxin's effect, except at the highest concentration (AMB, 100 microg/ml). Similarly, the higher nitrite levels observed after exposure of the cells to 6-OHDA were only partially reversed by AMB, at this highest concentration. However, when AMB (0.5, 1, 10 and 100 microg/ml) was added before the toxin, it appeared to protect neuronal cells against 6-OHDA toxicity in a concentration-dependent manner, as shown by MTT assay. AMB also prevented free radical formation indicated by the increased nitrite concentration induced by 6-OHDA. Cells exposed to 6-OHDA showed a 3.4 times increase in TBARS concentration as compared to controls, and this effect was inhibited from 24% up to 64% by AMB (0.1-100 microg/ml), indicative of a neuroprotective effect. In conclusion, we show that AMB, acting as an antioxidant compound, presents a significant neuroprotective effect, suggesting that this compound could provide benefits as a therapeutic agent in neurodegenerative disease such as Parkinson's.

This study reports the antimitotic effects on sea urchin eggs of five known pterocarpans: (+)-3,10-dihydroxy-9-methoxypterocarpan, (+)-3,9-dimethoxypterocarpan [(+)-homopterocarpin], (+)-2,3,9-trimethoxypterocarpan, (+)-3,4-dihydroxy-9-methoxypterocarpan [(+)-vesticarpan] and (+)-3-hydroxy-9-methoxypterocarpan [(+)-medicarpin], isolated from the trunk of Platymiscium floribundum, a native tree from Brazil. All tested compounds showed strong activity in this assay, with 2,3,9-trimethoxypterocarpan being the most active (log IC50 of -8.10 +/- 0.02; -7.91 +/- 0.01; -7.97 +/- 0.02 M for first and third cleavages, and blastulae stages, respectively). These data suggest that the 2-methoxy substituent can be an important pharmacophoric unit.

In Brazil, a herbal medicinal extract named Catuama containing a mixture of Paullinia cupana (guarana; Sapindaceae), Trichilia catigua (catuaba; Meliaceae), Ptychopetalum olacoides (muirapuama; Olacaceae) and Zingiber officinale (ginger; Zingiberaceae) is used as a body stimulant, energetic, tonic and aphrodisiac. The present study investigated the chronic administration of 25 mL Catuama twice a day during 28 days for any toxic effect on healthy human volunteers of both sexes. No severe adverse reactions or haematological and biochemical changes were reported., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

(1a S*,1b S*,7a S*,8a S*)-4,5-Dimethoxy-1a,7a-dimethyl-1,1a,1b,2,7, 7a,8,8a-octahydrocyclopropa cyclopenta[1,2-b]naphthalene-3,6-dione (1), a new meroterpenoid benzoquinone, and microphyllaquinone (2), a known naphthoquinone, have been isolated from roots of Cordia globosa. Both structure determinations were performed by conventional spectroscopic methods, including inverse detection NMR techniques, and by comparison with data from the literature for related compounds. Compound 1 displayed considerable cytotoxic activity against several cancer cell lines with IC50 values in the range of 1.2 to 5.0 microg/mL. The cytotoxic activity seemed to be related to DNA synthesis inhibition, as revealed by the reduction of 5-bromo-2'-deoxyuridine incorporation, and apoptosis induction, as indicated by the acridine orange/ethidium bromide assay and morphological changes after 24 h of incubation on leukemic cells.

Phytochemical analysis of the leaves of Acnistus arborescens (Solanaceae) resulted in the isolation of two new epimeric withaphysalins (17S,20R,22R)-5beta,6beta: 18,20-diepoxy-4beta,18-dihydroxy-1-oxowitha-24-enolide (2, 18R and 18S), together with the known withaphysalin F (1, 18R and 18S). Their structures were established by spectroscopic methods, including 2D NMR data and comparison with literature data. Compounds 1 and 2 dis-played potent cytotoxic activities against several cancer cell lines with IC50 values in the range of 0.20 to 1.46 microg/mL for 1 and 0.89 to 8.08 microg/mL for 2. The strong cytotoxicity presented by 1 suggests that in this series of compounds, the 2,3-unsaturated ketone moiety is an important pharmacophoric unit. The cytotoxic activity seemed to be related to DNA synthesis inhibition, as revealed by the reduction of 5-bromo-2'-deoxyuridine incorporation after 24 hours of incubation on leukemic cells.

Five abietane diterpenes were isolated from a hexane extract obtained from the roots of Aegiphila lhotzkyana and identified as uncinatone, cyrtophyllone B, teunvicenone E, sugiol and 12,16-epoxy-11,14-dihydroxy-6-methoxy-17(15 - 16)- abeo-abieta-5,8, 11,13,15-pentaene-3,7-dione. The last compound has only been described for this species. These compounds were tested for their antiproliferative effects on tumor cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl- 2H-tetrazolium bromide (MTT) assay and on sea urchin egg development, as well as for their lytic properties on mouse erythrocytes. All diterpenes reduced the viability of tumor cells and inhibited sea urchin egg cleavage. None of the tested compounds presented hemolytic activity.

In the present study, it was demonstrated that the hexanic extract obtained from the roots of Lonchocarpus sericeus and one of its major components, derricin, but not lonchocarpin, show cytotoxic activity to fertilized sea urchin eggs. Both inhibited the first cleavage of sea urchin eggs in a dose-dependent manner with an IC(50) of 30.4 (26.2-35.3) microgram/mL for the crude extract and 51.2 (42.1-62.3) microgram/mL for derricin (n = 6, in both cases). Furthermore, the hexanic extract of L. sericeus, and the isolated compounds, derricin and lonchocarpin showed cytotoxicity against CEM leukaemic cell line (IC(50) = 17.6 (13.7-22.6), 13.0 (12.0-14.0) and 10.4 (5.6-19.1) microgram/ml (n = 6), respectively). When these substances (6.25 to 125 microgram/25 microL) were examined for antimicrobial activity against Escherichia coli, Staphylococcus aureus and Candida albicans, none of them were found to be active. Neither the hexanic extract, nor the isolated compounds derricin and lonchocarpin (0.5 to 250 microgram/mL) presented hemolytic activity. These results indicated a possible antimitotic activity of L. sericeus crude extract and their major constituents., (Copyright 2003 John Wiley & Sons, Ltd.)