Nonclinical Toxicological Studies of Brazilian Red Propolis and Its Primary Botanical Source Dalbergia ecastaphyllum.

Propolis is one of the most widely used products in traditional medicine. One of the most prominent types of Brazilian propolis is the red one, whose primary botanical source is Dalbergia ecastaphyllum (L.) Taub. Despite the potential of Brazilian red propolis for developing new products with pharmacological activity, few studies guarantee safety in its use. The objective of this study was the evaluation of the possible toxic effects of Brazilian red propolis and D. ecastaphyllum, as well as the cytotoxicity assessment of the main compounds of red propolis on tumoral cell lines. Hydroalcoholic extracts of the Brazilian red propolis (BRPE) and D. ecastaphyllum stems (DSE) and leaves (DLE) were prepared and chromatographed for isolation of the major compounds. RP-HPLC-DAD was used to quantify the major compounds in the obtained extracts. The XTT assay was used to evaluate the cytotoxic activity of the extracts in the human fibroblast cell line (GM07492A). The results revealed IC50 values of 102.7, 143.4, and 253.1 µg/mL for BRPE, DSE, and DLE, respectively. The extracts were also evaluated for their genotoxic potential in the micronucleus assay in Chinese hamster lung fibroblasts cells (V79), showing the absence of genotoxicity. The BRPE was investigated for its potential in vivo toxicity in the zebrafish model. Concentrations of 0.8-6.3 mg/L were safe for the animals, with a LC50 of 9.37 mg/L. Of the 11 compounds isolated from BRPE, medicarpin showed a selective cytotoxic effect against the HeLa cell line. These are the initial steps to determine the toxicological potential of Brazilian red propolis.

Ruthenium(II) Diphosphine Complexes with Mercapto Ligands That Inhibit Topoisomerase IB and Suppress Tumor Growth In Vivo.

Ruthenium(II) complexes (Ru1-Ru5), with the general formula [Ru(N-S)(dppe)2]PF6, bearing two 1,2-bis(diphenylphosphino)ethane (dppe) ligands and a series of mercapto ligands (N-S), have been developed. The combination of these ligands in the complexes endowed hydrophobic species with high cytotoxic activity against five cancer cell lines. For the A549 (lung) and MDA-MB-231 (breast) cancer cell lines, the IC50 values of the complexes were 288- to 14-fold lower when compared to cisplatin. Furthermore, the complexes were selective for the A549 and MDA-MB-231 cancer cell lines compared to the MRC-5 nontumor cell line. The multitarget character of the complexes was investigated by using calf thymus DNA (CT DNA), human serum albumin, and human topoisomerase IB (hTopIB). The complexes potently inhibited hTopIB. In particular, complex [Ru(dmp)(dppe)2]PF6 (Ru3), bearing the 4,6-diamino-2-mercaptopyrimidine (dmp) ligand, effectively inhibited hTopIB by acting on both the cleavage and religation steps of the catalytic cycle of this enzyme. Molecular docking showed that the Ru1-Ru5 complexes have binding affinity by active sites on the hTopI and hTopI-DNA, mainly via π-alkyl and alkyl hydrophobic interactions, as well as through hydrogen bonds. Complex Ru3 displayed significant antitumor activity against murine melanoma in mouse xenograph models, but this complex did not damage DNA, as revealed by Ames and micronucleus tests.

Influence of Asiatic acid on cell proliferation and DNA damage in vitro and in vivo systems.

Asiatic acid (AA) is a triterpene with promising pharmacological activity. In the present study, in vitro and in vivo assays were conducted to understand the effect of AA on cell proliferation and genomic instability. AA was cytotoxic to human tumor cell lines (M059J, HeLa, and MCF-7), with IC50 values ranging from 13.91 to 111.72 µM. In the case of M059J, AA exhibited selective cytotoxicity after 48 h of treatment (IC50 = 24 µM), decreasing the percentage of cells in the G0/G1 phase, increasing the percentage of cells in the S phase, and inducing apoptosis. A significant increase in chromosomal damage was observed in V79 cell cultures treated with AA (40 µM), revealing genotoxic activity. In contrast, low concentrations (5, 10, and 20 µM) of AA significantly reduced the frequencies of micronuclei induced by the mutagens doxorubicin (DXR), methyl methanesulfonate, and hydrogen peroxide. A reduction of DXR-induced intracellular free radicals was found in V79 cells treated with AA (10 µM). The antigenotoxic effect of AA (30 mg/kg) was also observed against DXR-induced chromosomal damage in Swiss mice. Significant reductions in p53 levels were verified in the liver tissue of these animals. Taken together, the data indicate that AA exerted antiproliferative activity in M059J tumor cells, which is probably related to the induction of DNA damage, leading to cell cycle arrest and apoptosis. Additionally, low concentrations of AA exhibited antigenotoxic effects and its antioxidant activity may be responsible, at least in part, for chemoprevention.

Betulinic acid exerts antigenotoxic and anticarcinogenic activities via inhibition of COX-2 and PCNA in rodents.

Phytochemicals have been suggested as an effective strategy for cancer prevention. Within this context, triterpene betulinic acid (BA) exhibits several biological properties but its chemopreventive effect has not been fully demonstrated. The present study investigated the antigenotoxic potential of BA against doxorubicin (DXR)-induced genotoxicity using the mouse peripheral blood micronucleus assay, as well as its anticarcinogenic activity against 1,2dimethylhydrazine (DMH)-induced colorectal lesions in rats. Micronuclei (MN) assay and aberrant crypt foci assay were used to assess the antigenotoxic and the anticarcinogenic potential, respectively. The molecular mechanisms underlying the anticarcinogenic activity of BA were evaluated by assessing anti-inflammatory (COX-2) and antiproliferative (PCNA) pathways. The results demonstrated that BA at the dose of 0.5 mg/kg bodyweight exerted antigenotoxic effects against DXR, with a reduction of 70.2% in the frequencies of chromosomal damage. Animals treated with BA showed a 64% reduction in the number of preneoplastic lesions when compared to those treated with the carcinogen alone. The levels of COX-2 and PCNA expression in the colon were significantly lower in animals treated with BA and DMH compared to those treated with the carcinogen alone. The chemopreventive effect of BA is related, at least in part, to its antiproliferative and anti-inflammatory activity, indicating a promising potential of this triterpene in anticancer therapies, especially for colorectal cancer.

Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct-[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine], by in vitro and in vivo assays.

Considering the promising previous results of ct-[RuCl(CO)(dppb)(bipy)]PF6 (where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2'-bipyridine) as an antitumor agent, novel biological assays evaluating its toxicogenic potential were performed. The genotoxicity of the compound was evaluated by the in vitro micronucleus test (V79, Chinese hamster lung fibroblasts; HepG2, hepatocellular carcinoma cells), in vivo bone marrow micronucleus test and comet assay in hepatocytes (Swiss mice). The animals were treated with 0.63, 1.25, 2.5 and 5.0 mg/kg body weight (bw) of the compound. Negative (water) and positive (cisplatin, 1.5 mg/kg bw; methyl methanesulfonate, 40 mg/kg bw) controls were included. The parameters considered in the comet assay were the percentage of tail DNA, tail moment and tail length. The results of the in vitro micronucleus tests showed the absence of genotoxicity in V79 cells, while the compound was genotoxic in HepG2 cells at a concentration of 1.25 µm. In the in vivo micronucleus test, the compound was not genotoxic at the different doses evaluated. In the comet assay, only the dose of 5.0 mg/kg bw resulted in a significant increase in the frequency of DNA damage in hepatocytes when compared to the negative control. The genotoxic effect observed in HepG2 cells and in the liver comet assay indicates that the compound was metabolized by hepatic cells.

Chemical Composition, Antibacterial, Schistosomicidal, and Cytotoxic Activities of the Essential Oil of Dysphania ambrosioides (L.) Mosyakin & Clemants (Chenopodiaceae).

We have investigated the chemical composition and the antibacterial activity of the essential oil of Dysphania ambrosioides (L.) Mosyakin & Clemants (Chenopodiaceae) (DA-EO) against a representative panel of cariogenic bacteria. We have also assessed the in vitro schistosomicidal effects of DA-EO on Schistosoma mansoni and its cytotoxicity to GM07492-A cells in vitro. Gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS) revealed that the monoterpenes cis-piperitone oxide (35.2%), p-cymene (14.5%), isoascaridole (14.1%), and α-terpinene (11.6%) were identified by as the major constituents of DA-EO. DA-EO displayed weak activity against Streptococcus sobrinus and Enterococcus faecalis (minimum inhibitory concentration (MIC) = 1000 µg/ml). On the other hand, DA-EO at 25 and 12.5 µg/ml presented remarkable schistosomicidal action in vitro and killed 100% of adult worm pairs within 24 and 72 h, respectively. The LC50 values of DA-EO were 6.50 ± 0.38, 3.66 ± 1.06, and 3.65 ± 0.76 µg/ml at 24, 48, and 72 h, respectively. However, DA-EO at concentrations higher than 312.5 µg/ml significantly reduced the viability of GM07492-A cells (IC50  = 207.1 ± 4.4 µg/ml). The selectivity index showed that DA-EO was 31.8 times more toxic to the adult S. mansoni worms than GM07492-A cells. Taken together, these results demonstrate the promising schistosomicidal potential of the essential oil of Dysphania ambrosioides.

Schistosomicidal Effects of the Essential Oils of Citrus limonia and Citrus reticulata Against Schistosoma mansoni.

We report the in vitro schistosomicidal effects of the essential oil obtained from Citrus limonia leaves (CL-EO) and C. reticulata fruit peels (CR-EO), cultivated in Brazil, against Schistosoma mansoni worms. Limonene (29.9%), ß-pinene (12.0%), sabinene (9.0%), citronellal (9.0%), and citronellol (5.8%) are the major constituents of CL-EO; limonene (26.5%), γ-terpinene (17.2%), linalool (11.1%), octanal (8.0%), myrcene (6.2%), and capraldehyde (3.9%) predominate in CR-EO. CL-EO displayed moderate lethal concentration 50% (LC50 ) of 81.7 and 38.9 µg/ml against male and female worms at 24 and 72 h, respectively. At concentrations of 25 and 100 µg/ml, CL-EO separated between 50 and 75% of the coupled worm pairs during the evaluated period. CR-EO presented moderate LC50 of 81.7 µg/ml against male and female worms at 24 and 72 h. However, this oil separated coupled worm pairs more effectively than CL-EO and displayed lower cytotoxicity to GM07492-A cells (IC50 = 987.7 ± 88.9 µg/ml) as compared to CL-EO (IC50 = 187.8 ± 2.9 µg/ml). The enantiomers (+)-(R)-limonene and (-)-(S)-limonene did not affect S. mansoni adult worm pairs significantly. Taken together, these data indicate that CL-EO and CR-EO exhibit moderate in vitro schistosomicidal activity against adult S. mansoni worms.

Incorporation of anti-inflammatory agent into mesoporous silica.

The unique properties of macroporous, mesoporous, and microporous systems, including their ability to accommodate molecules of different sizes inside their pores and to act as drug delivery systems, have been the object of extensive studies. In this work, mesoporous silica with hexagonal structure was obtained by template synthesis via the sol-gel process. The resulting material was used as support to accommodate the anti-inflammatory agent indomethacin. The alkaline route was used to prepare the mesoporous silica; cetyltrimethylammonium bromide was employed as porogenic agent. The silica particles were functionalized with 3-aminopropyltriethoxysilane alkoxide (APTES) by the sol-gel post-synthesis method. Indomethacin was incorporated into the silica functionalized with APTES and into non-functionalized silica. The resulting systems were characterized by x-ray diffraction (XRD), specific area, infrared spectroscopy, and thermal analyses (TGA). XRD attested to formation of mesoporous silica with hexagonal structure. This structure remained after silica functionalization with APTES and incorporation of indomethacin. Typical infrared spectroscopy vibrations and organic material decomposition during TGA confirmed silica functionalization and drug incorporation. The specific surface area and pore volume of the functionalized material incorporated with indomethacin decreased as compared with the specific surface area and pore volume of the non-functionalized silica containing no drug, suggesting both the functionalizing agent and the drug were present in the silica. Cytotoxicity tests conducted on normal fibroblasts (GM0479A) cells attested that the silica matrix containing indomethacin was less toxic than the free drug.

Copaifera duckei Oleoresin and Its Main Nonvolatile Terpenes: In Vitro Schistosomicidal Properties.

In this article, the in vitro schistosomicidal effects of three Brazilian Copaifera oleoresins (C. duckei, C. langsdorffii, and C. reticulata) are reported. From these botanical sources, the oleoresin of C. duckei (OCd) demonstrated to be the most promising, displaying LC50 values of 75.8, 50.6, and 47.2 µg/ml at 24, 48, and 72 h of incubation, respectively, against adult worms of Schistosoma mansoni, with a selectivity index of 10.26. Therefore, the major compounds from OCd were isolated, and the diterpene, (-)-polyalthic acid (PA), showed to be active (LC50 values of 41.7, 36.2, and 33.4 µg/ml, respectively, at 24, 48, and 72 h of incubation). Moreover, OCd and PA affected the production and development of eggs, and OCd modified the functionality of the tegument of S. mansoni. Possible synergistic and/or additive effects of this balsam were also verified when a mixture of the two of its main compounds (PA and ent-labd-8(17)-en-15,18-dioic acid) in the specific proportion of 3:1 (w/w) was tested. The obtained results indicate that PA should be considered for further investigations against S. mansoni, such as, synergistic (combination with praziquantel (PZQ)) and in vivo studies. It also shows that diterpenes are an important class of natural compounds for the investigation of agents capable of fighting the parasite responsible for human schistosomiasis.

Anthelmintic effects of the essential oil of fennel (Foeniculum vulgare Mill., Apiaceae) against Schistosoma mansoni.

Foeniculum vulgare Mill. (Apiaceae), known as fennel, is a widespread aromatic herbaceous plant, and its essential oil is used as additive in the food, pharmaceutical, cosmetic, and perfume industries. The in vitro antischistosomal activity and cytotoxic effects against V79 cells of the essential oil of F. vulgare cultivated in southeastern Brazil (FV-EO) was investigated. The FV-EO was obtained by hydrodistillation and characterized by GC-FID and GC/MS analyses. (E)-Anethole (69.8%) and limonene (22.5%) were identified as the major constituents. Its anthelmintic activity against Schistosoma mansoni was evaluated at concentrations of 10, 50, and 100 µg/ml, and it was found to be active against adult S. mansoni worms, although it was less effective than the positive control praziquantel (PZQ) in terms of separation of the coupled pairs, mortality, and decreased motor activity. However, FV-EO elicited an interesting dose-dependent reduction in the number of S. mansoni eggs. On their own, (E)-anethole and the limonene enantiomers were much less effective than FV-EO and PZQ. An XTT-cytotoxicity-based assay evidenced no FV-EO cytotoxicity against V79 cells. In summary, FV-EO displayed moderate in vitro schistosomicidal activity against adult S. mansoni worms, exerted remarkable inhibitory effects on the egg development, and was of low toxicity.

Chemopreventive effects of (-)-hinokinin against 1,2-dimethylhydrazine-induced genotoxicity and preneoplastic lesions in rat colon.

(-)-Hinokinin (1) is a dibenzylbutyrolactone lignan obtained by the partial synthesis of (-)-cubebin. This study reports the antigenotoxic and anticarcinogenic potential of 1 by the comet and aberrant crypt focus assays in the peripheral blood and colon of 4-5-week-old Wistar rats, respectively. The rats were exposed to 1,2-dimethylhydrazine (40 mg/kg) and were treated by gavage with doses of 10, 20, and 40 mg/kg of 1. The results showed that the dose of 40 mg/kg was neither genotoxic nor carcinogenic. In the comet assay, all 1 doses displayed antigenotoxic effects. In addition, this compound (20 and 40 mg/kg) exhibited an anticarcinogenic effect in the aberrant crypt focus assay.

Facilitating Seed Iron Uptake through Amine-Epoxide Microgels: A Novel Approach to Enhance Cucumber (Cucumis sativus) Germination.

Enhancing the initial stages of plant growth by using polymeric gels for seed priming presents a significant challenge. This study aimed to investigate a microgel derived from polyetheramine-poly(propylene oxide) (PPO) and a bisepoxide (referred to as micro-PPO) as a promising alternative to optimize the seed germination process. The micro-PPO integrated with an iron micronutrient showed a positive impact on seed germination compared with control (Fe solutions) in which the root length yield improved up to 39%. Therefore, the element map by synchrotron-based X-ray fluorescence shows that the Fe intensities in the seed primers with the micro-PPO-Fe gel are about 3-fold higher than those in the control group, leading to a gradual distribution of Fe species through most internal embryo tissues. The use of micro-PPO for seed priming underscores their potential for industrial applications due to the nontoxicity results in zebrafish assays and environmentally friendly synthesis of the water-dispersible monomers employed.

Polyalthic Acid from Copaifera lucens Demonstrates Anticariogenic and Antiparasitic Properties for Safe Use.

This study aimed at evaluating the potential of Copaifera lucens, specifically its oleoresin (CLO), extract (CECL), and the compound ent-polyalthic acid (PA), in combating caries and toxoplasmosis, while also assessing its toxicity. The study involved multiple assessments, including determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against cariogenic bacteria. CLO and PA exhibited MIC and MBC values ranging from 25 to 50 µg/mL, whereas CECL showed values equal to or exceeding 400 µg/mL. PA also displayed antibiofilm activity with minimum inhibitory concentration of biofilm (MICB50) values spanning from 62.5 to 1000 µg/mL. Moreover, PA effectively hindered the intracellular proliferation of Toxoplasma gondii at 64 µg/mL, even after 24 h without treatment. Toxicological evaluations included in vitro tests on V79 cells, where concentrations ranged from 78.1 to 1250 µg/mL of PA reduced colony formation. Additionally, using the Caenorhabditis elegans model, the lethal concentration (LC50) of PA was determined as 1000 µg/mL after 48 h of incubation. Notably, no significant differences in micronucleus induction and the NDI were observed in cultures treated with 10, 20, or 40 µg/mL of CLO. These findings underscore the safety profile of CLO and PA, highlighting their potential as alternative treatments for caries and toxoplasmosis.

Volatile compounds of hexane extract from Pterodon pubescens Benth seeds and its significant in vitro potential against different bacterial strains.

Pterodon pubescens Benth is a Brazilian medicinal plant (sucupira, in Brazilian Portuguese). This paper aims to determine the volatile composition and antibacterial activities of hexane extract from P. pubescens seeds (HE-PP). Antibacterial activities were screened by the microdilution broth method in 96-well culture plates and MIC values were expressed as µg/mL. HE-PP was active against several oral bacteria whose MIC values ranged between 12.5 µg/mL and 50 µg/mL and against three mycobacterial strains (MIC = 125 µg/mL and 500 µg/mL). In addition, HE-PP was active against Xanthomonas citri strain (MIC = 100 µg/mL). Cytotoxic activity of the extract was evaluated in human tumour and non-tumour cell lines. HE-PP showed selective cytotoxicity to cervical adenocarcinoma (HeLa cells - IC50 = 53.47 µg/mL). Its major constituents were identified by GC-MS and GC-FID: E-caryophyllene, vouacapane, E-geranylgeraniol and dehydroabietol. Results reinforce the biological potential of HE-PP against a broad spectrum of pathogenic and phytopathogenic bacteria.

Hexane extracts from fruit of two varieties of Capsicum chinense Jacq.: their volatile constituents and antiacetylcholinesterase, antileishmanial and antiproliferative activities.

This article aims to investigate volatile constituents and antiacetylcholinesterase, antileishmanial and antiproliferative activities of hexane extracts from Capsicum chinense fruit (unripe bode pepper 'HE-UB' and ripe little beak pepper 'HE-RB'). HE-UB and HE-RB were screened by the microplate assay method to determine their antiacetylcholinesterase activity. Both exhibited inhibitory potential, i. e., IC50 = 41.5 and 20.3 µg/mL, respectively. HE-UB (IC50 = 67.19 µg/mL) and HE-RB (IC50 = 38.16 µg/mL) exhibited antileishmanial activity against promastigote forms of Leishmania (Leishmania) amazonensis. In addition, HE-UB and HE-RB demonstrated cytotoxic activity against different human tumor cell lines with IC50 ranging from 325.40 to 425.0 µg/mL. Both GC-FID and GC-MS analyses revealed that the major component in both extracts was E-caryophyllene. In short, HE-RB was more satisfactory than HE-UB in all in vitro activities under evaluation. These findings may be used as initial data for further studies of Capsicum species.

EF24, a schistosomicidal curcumin analog: Insights from its synthesis and phenotypic, biochemical and cytotoxic activities.

Praziquantel (PZQ) is the only drug available for community-based control programs which aim to reduce the prevalence and morbidity associated with schistosomiasis. Here, we synthesized and evaluated the schistosomicidal, biochemical and cytotoxic activities of EF24, a synthetic curcumin analog, against different isolates of Schistosoma mansoni. EF24 elicited marked phenotypic alterations at 10 µM against schistosomula and 42-day-old adult worms of the Naval Medical Research Institute (NMRI) isolate. EF24 had 50% effective concentration (EC50) values of <10 µM against the Luis Evangelista (LE), Sergipe (SE), Belo Horizonte (BH) and Belo Horizonte less sensitive to PZQ (BH < PZQ) isolates of adult S. mansoni; however, the respective sensitivities of these isolates differed. Changes in the parasite included, vacuolization of the tegument and focal lysis of the interstitial tissue and muscle layers. Against 28-day-old juvenile worms (LE isolate), EF24 was about three times more potent than PZQ. After 6 h at 12.5 µM, EF24 increased reactive oxygen species (ROS) and the activity of the antioxidant enzyme, glutathione-S-transferase (GST), by 32 and 19% in female and male adult worms, respectively. By contrast, after 6 h at 12.5 µM glutathione reductase (GR) activity decreased by 43 and 30%, and glutathione peroxidase (GPx) activity decreased by 67 and 44% in females and males, respectively. EF24 was less cytotoxic to mammalian host cells than to S. mansoni, with selectivity indexes (SIs) of 1.8-3.4 and 2.7-7.5 for juvenile and adult worms, respectively. Given the current evidence for the in vitro schistosomicidal effect of EF24, the structure-activity relationship of additional analogs to identify new candidates for schistosomiasis treatment is warranted.

Chemical composition and in vitro schistosomicidal activity of the essential oil of Plectranthus neochilus grown in Southeast Brazil.

The chemical composition and the in vitro schistosomicidal effects of the essential oil of Plectranthus neochilus (PN-EO) grown in Southeast Brazil was studied. ß-Caryophyllene (1; 28.23%), α-thujene (2; 12.22%), α-pinene (3; 12.63%), ß-pinene (4; 6.19%), germacrene D (5; 5.36%), and caryophyllene oxide (6; 5.37%) were the major essential oil constituents. This chemical composition differed from that previously reported for specimens harvested in Africa. Concerning the in vitro schistosomicidal activity against adult Schistosoma mansoni worms, PN-EO was considered to be active, but less effective than the positive control praziquantel (PZQ) in terms of separation of coupled pairs, mortality, decrease in the motor activity, and tegumental alterations. However, PN-EO caused an interesting dose-dependent reduction in the number and the percentage of developed S. mansoni eggs. These results suggest that PN-EO might be very promising for the development of new schistosomicidal agents.

Biological properties and chemical composition of essential oil from Nectandra megapotamica (Spreng.) Mez. leaves (Lauraceae).

Nectandra megapotamica is a tree species that naturally occurs in the Atlantic Forest, Brazil. This paper aims to investigate the chemical composition and in vitro antibacterial, antileishmanial and antiproliferative activities of essential oil from N. megapotamica leaves (NM-EO). It displayed high antibacterial activity against Streptococcus mutans, S. sobrinus, Prevotella nigrescens and Bacteroides fragilis. NM-EO also exhibited high antileishmanial activity against promastigote forms of Leishmania amazonensis. Its antiproliferative activity was evaluated against the following cells: GM07429A (normal cell), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma) and M059J (human glioblastoma). Its major components, which were determined by GC-FID and GC-MS, were α-bisabolol (13.7%), bicyclogermacrene (10.9%), (E,E)-farnesene (10.6%), Z-caryophyllene (9.5%) and (E)-ß-farnesene (7.0%). These results suggest that N. megapotamica, a Brazilian plant, shows initial evidence of a new and alternative source of substances of medicinal interest.

Chemical composition and in vitro antibacterial and antiproliferative activities of the essential oil from the leaves of Psidium myrtoides O. Berg (Myrtaceae).

In this study, the chemical composition and antibacterial and antiproliferative potential of the essential oil obtained from fresh leaves of Psidium myrtoides (PM-EO) against oral pathogens and human tumour cell lines were investigated for the first time. GC-FID and GC-MS analyses showed that trans-ß-caryophyllene (30.9%), α-humulene (15.9%), α-copaene (7.8%), caryophyllene oxide (7.3%) and α-bisabolol (5.3%) are the major constituents of PM-EO. The antibacterial activity of PM-EO against a panel of oral pathogens was investigated in terms of their minimal inhibitory concentrations (MIC) using the broth microdilution method. PM-EO displayed moderate activity against Streptococcus mitis (MIC = 100 µg/mL), S. sanguinis (MIC = 100 µg/mL), S. sobrinus (MIC = 250 µg/mL), and S. salivarius (MIC = 250 µg/mL), and strong activity against S. mutans (MIC = 62.5 µg/mL). The antiproliferative activity in normal (GM07492A, lung fibroblasts) and tumour cell lines (MCF-7, HeLa, and M059 J) was performed using the XTT assay. PM-EO showed 50% inhibition of normal cell growth at 359.8 ± 6.3 µg/mL. Antiproliferative activity was observed against human tumour cell lines, with IC50 values significantly lower than that obtained for the normal cell line, demonstrating IC50 values for MCF-7 cells (254.5 ± 1.6 µg/mL), HeLa cells (324.2 ± 41.4 µg/mL) and M059 J cells (289.3 ± 10.9 µg/mL). Therefore, the cytotoxicity of PM-EO had little influence on the antibacterial effect, since it showed antibacterial activity at lower concentrations. Our results suggest that PM-EO is a promising source of new antibacterial and antitumour agents.

Eugenia pyriformis Cambess: a species of the Myrtaceae family with bioactive essential oil.

Eugenia species have been appreciated for their edible fruits and medicinal properties. This paper aims to investigate the chemical composition and in vitro antileishmanial, antifungal and antiproliferative activities of essential oil from aerial parts of Eugenia pyriformis (EP-EO). The oil showed strong antileishmanial activity against promastigote forms of Leishmania amazonensis (IC50 = 2.16 µg/mL). It also exhibited high antifungal activity against Malassezia furfur (MIC = 30 µg/mL), which was determined by the broth microdilution method. Its antiproliferative activity was evaluated against the following cells: GM07429A (normal cell), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma) and M059J (human glioblastoma). Its major constituents, which were determined by GC-FID and GC-MS, were limonene (14.8%), nerolidol (11.0%), α-cadinol (10.3%), caryophyllene oxide (9.9%) and ß-pinene (7.1%). These results showed, for the first time, the effectiveness of EP-EO as a natural product which has promising biological activities, a fact that enables its ethnopharmacological use.