Evaluation of non-clinical toxicity of extract and vouacapans from fruits of Pterodon pubescens Benth.

Pterodon pubescens Benth. is widely used in folk medicine for the treatment of inflammatory conditions, with the activity attributed to the compounds with a vouacapan moiety, however, few studies report the toxicological evaluation of the extract and safety issues related to the species. Herein the non-clinical toxicity, in in vivo and in vitro tests, of dichloromethane crude extract of Pterodon pubescens fruits (PPE) and vouacapan diterpene furan isomer´s mixture (1:1) 6α-hydroxy-7ß-acetoxy-vouacapan-17ß-oate methyl ester and 6α-acetoxy-7ß-hydroxy-vouacapan-17ß-oate methyl ester isomers (VDFI mixture) is reported. Toxicological evaluation of 110-day repeated dose oral toxicity study, as hematological, biochemical, and histopathological parameters demonstrated that animals (male and female Wistar rats) treated with PPE presented no signs of toxicity, nevertheless daily high dose administration (500 mg/Kg) altered the metabolic homeostasis of animals that manifested microgoticular hepatic steatosis. Biochemical and histopathological results of animals (female Swiss mice) treated daily with VDFI mixture, at the highest dose (300 mg/Kg), indicated liver toxicity in one animal causing acute hepatotoxicity. Alkaline Comet assay demonstrated that PPE and VDFI mixture increased the percentage of DNA fragmentation without interfering with the tail moment parameter, but only VDFI mixture (30 µg/mL) presented statistical difference. In the micronucleus induction test, PPE and VDFI mixture did not demonstrate mutagenic potential. Our data provide evidence for the safety use of PPE and VDFI mixture in lower doses enabling further clinical studies and the development of herbal medicine.

Phytocosmetic Containing Pink Pepper Extracts Obtained by Sustainable Extraction.

Pink pepper (Schinus terebinthifolius Raddi) has high potential for commercial use because of its biological activities (anti-inflammatory, antitumor, and antioxidant activities, among others). Herein, the antioxidant activity of a topical formulation containing pink pepper extract obtained by supercritical carbon dioxide extraction is reported. The effects of extraction pressure (100-300 bar) and temperature (40-60 °C) on its antioxidant activity were investigated. The extracts obtained at 50-60 °C showed a higher inhibition percentage in the α,α-diphenyl-ß-picrylhydrazyl (DPPH) assay (80.16-91.27 %), regardless of pressure. The extract obtained under optimized conditions (200 bar and 50 °C) was incorporated into an oil-in-water emulsion containing 2 % (m/m) pink pepper extract. The product presented a creamy texture, light rose color, mild spicy odor, and desirable pH for a topical formulation. Furthermore, the product was stable and remained effective when stored and protected from heat and light, showing 35.38 % inhibition of DPPH.

Gastrointestinal effects of Mentha aquatica L. essential oil.

Found in humid regions and waterways and popularly used to treat gastrointestinal problems among other applications, the present study evaluated the M. aquatica essential oil (OEMa) as a therapeutic alternative to treat gastrointestinal disorders. Produced by steam distillation, chemical composition of OEMa was determined by GC-MS analysis. The ethanol-induced ulcer and the dose-repeated acetylsalicylic acid (ASA)-induced gastrointestinal lesions models in rats evaluated, respectively, the prophylactic and curative effects of EOMa on peptic ulcers. The EOMa's effect on gastric secretion, gastric mucus and gastrointestinal motility were evaluated in in vivo models. The curative effect of EOMa on acute colitis was evaluated using the DSS-induced colitis model in mice. Obtained in 0.17% yield (w/w), with carvone (54.82 ± 1.39 g/100 g oil) as the main constituent, EOMa (at 75 mg/kg) showed potent gastroprotective effect (> 90%) mediated by non-protein sulfhydryl compounds (NPSH) and nitric oxide (NO) modulation alongside reduction in gastric secretion volume and total acidity. EOMa did not affect gastric mucus production and gastrointestinal motility. In dose-repeated ASA-induced gastrointestinal lesions model, EOMa (at 25 mg/kg) promoted the inflammatory process resolution both in gastric and duodenal walls by modulating NPSH, NO and myeloperoxidase levels. Despite delaying in 2 days the clinical symptoms worsening, EOMa (at 25 mg/kg) was not able to protect colon tissues from DSS-induced acute colitis as evidenced by macroscopic, biochemical, and histopathological parameters. This is the first report of Mentha aquatica essential oil as a promising herbal medicine for peptic ulcers treatment together with an adjuvant effect in IBD.

Antiproliferative Effects of Pterodon pubescens Extract and Isolated Diterpenes in HaCaT Cells.

Pterodon pubescens fruits are popularly used because of their analgesic and anti-inflammatory actions, which are attributed to the isolated compounds with a vouacapan skeleton. This work aimed to evaluate the antiproliferative and anti-inflammatory effects of a P. pubescens fruit dichloromethane extract and the vouacapan diterpene furan isomer's mixture (1 : 1) (6α-hydroxy-7ß-acetoxy-vouacapan-17ß-oate methyl ester and 6α-acetoxy-7ß-hydroxy-vouacapan-17ß-oate methyl ester isomers) in HaCaT cells using the cell migration and the BrDU incorporation assay. Levels of IL-8 were measured by ELISA after TNF-α stimulation. HPLC/DAD analysis of the extract revealed the expressive presence of vouacapan diterpene furan isomer's mixture. P. pubescens extract (1.5625 - 25 µg/mL) and vouacapan diterpene furan isomer's mixture (3.125 - 50 µM) inhibited cell proliferation as indicated by a decreased BrdU-incorporation. For the evaluation of cell migration, time-lapse microscopy was used. P. pubescens presented inhibition on cell migration at all concentrations tested (3.125 - 12.5 µg/mL), whereas for the VDFI mixture, the inhibition was only observed at the highest concentrations (12.5 and 25 µM) tested. Furthermore P. pubescens extract and vouacapan diterpene furan isomer's mixture significantly decreased IL-8 levels. Our results showed antiproliferative and anti-inflammatory effects on HaCaT cells treated with the extract and the vouacapan isomer's mixture, without affecting cell viability. These activities could be attributed to the voucapan molecular structures. In conclusion, topical products developed of P. pubescens extract or the voucapan isomer's mixture should be further studied as a potential product for local treatment against hyperproliferative lesions as in psoriasis vulgaris, representing an alternative treatment approach.

Açai (Euterpe oleracea Mart.) Seed Extract Induces ROS Production and Cell Death in MCF-7 Breast Cancer Cell Line.

Euterpe oleracea Mart. (açai) is a native palm from the Amazon region. There are various chemical constituents of açai with bioactive properties. This study aimed to evaluate the chemical composition and cytotoxic effects of açai seed extract on breast cancer cell line (MCF-7). Global Natural Products Social Molecular Networking (GNPS) was applied to identify chemical compounds present in açai seed extract. LC-MS/MS and molecular networking were employed to detect the phenolic compounds of açai. The antioxidant activity of açai seed extract was measured by DPPH assay. MCF-7 breast cancer cell line viability was evaluated by MTT assay. Cell death was evaluated by flow cytometry and time-lapse microscopy. Autophagy was evaluated by orange acridin immunofluorescence assay. Reactive oxygen species (ROS) production was evaluated by DAF assay. From the molecular networking, fifteen compounds were identified, mainly phenolic compounds. The açai seed extract showed cytotoxic effects against MCF-7, induced morphologic changes in the cell line by autophagy and increased the ROS production pathway. The present study suggests that açai seed extract has a high cytotoxic capacity and may induce autophagy by increasing ROS production in breast cancer. Apart from its antioxidant activity, flavonoids with high radical scavenging activity present in açai also generated NO (nitric oxide), contributing to its cytotoxic effect and autophagy induction.

Antiproliferative Flavanoid Dimers Isolated from Brazilian Red Propolis.

Herein reported are results of the chemical and biological investigation of red propolis collected at the Brazilian Northeast coastline. New propolones A-D (1-4), with a 3-{3-[(2-phenylbenzofuran-3-yl)methyl]phenyl}chromane skeleton; propolonones A-C (5-7), with a 3-[3-(3-benzylbenzofuran-2-yl)phenyl]chromane skeleton; and propolol A (8), with a 6-(3-benzylbenzofuran-2-yl)-3-phenylchromane skeleton, were isolated as constituents of Brazilian red propolis by cytotoxicity-guided assays and structurally identified by analysis of their spectroscopic data. Propolone B (2) and propolonone A (5) display significant cytotoxic activities against an ovarian cancer cell line expressing a multiple drug resistance phenotype when compared with doxorubicin.

Schinopsis brasiliensis Engl. to combat the biofilm-dependents diseases in vitro.

Dental caries and periodontal disease are the most prevalent of the biofilm-dependent diseases. With numerous side effects on the use of chlorhexidine, the search for new safe therapeutic alternatives for microorganisms involved with these diseases increases every day. This study aimed to evaluate the antimicrobial activity and cytotoxicity of extracts made from the bark of Schinopsis brasiliensis Engl. against five oral microorganisms and analyze their phytochemical and thermal degradation profile. The liquid-liquid partition was performed with hexane, chloroform and ethyl acetate. The identification and quantification of the chemical marker was done. Antimicrobial activity was evaluated based on the minimum inhibitory concentration. The cytotoxicity was analyzed based on the hemolysing potential of the samples. The thermal degradation profile was performed by two different methods. Gallic acid was identified as the main compound of the samples and showed the highest amount in the chloroform fraction. All samples were able to inhibit the growth of the microorganisms tested and showed no cytotoxicity. The ethanol extract absorbs less heat than the fractions. All samples exhibited exothermic peak consistent with degradation of gallic acid. Based on the results, the samples used are potential candidates for use in dental formulations for biofilm control.

Anti-Estrogenic Activity of Guajadial Fraction, from Guava Leaves (Psidium guajava L.).

The research of natural products has allowed for the discovery of biologically relevant compounds inspired by plant secondary metabolites, which contributes to the development of many chemotherapeutic drugs used in cancer treatment. Psidium guajava leaves present a diverse phytochemical composition including flavonoids, phenolics, meroterpenoids, and triterpenes as the major bioactive constituents. Guajadial, a caryophyllene-based meroterpenoid, has been studied for potential anticancer effects tested in tumor cells and animal experimental models. Moreover, guajadial has been reported to have a mechanism of action similar to tamoxifen, suggesting this compound as a promisor phytoestrogen-based therapeutic agent. Herein, the anti-estrogenic action and anti-proliferative activity of guajadial is reported. The enriched guajadial fraction was obtained by sequential chromatographic techniques from the crude P. guajava dichloromethane extract showing promising anti-proliferative activity in vitro with selectivity for human breast cancer cell lines MCF-7 and MCF-7 BUS (Total Growth Inhibition = 5.59 and 2.27 µg·mL-1, respectively). Furthermore, evaluation of anti-estrogenic activity in vivo was performed demonstrating that guajadial enriched fraction inhibited the proliferative effect of estradiol on the uterus of pre-pubescent rats. These results suggest a relationship between anti-proliferative and anti-estrogenic activity of guajadial, which possibly acts in tumor inhibition through estrogen receptors due to the compounds structural similarity to tamoxifen.

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.

In vitro SPF and Photostability Assays of Emulsion Containing Nanoparticles with Vegetable Extracts Rich in Flavonoids.

The aim of study was to determine the in vitro sun protection factor (SPF) and the photostability profile of a topical formulation composed of nanoparticles loaded with vegetable extracts and to assess its physicochemical properties. Chitosan/tripolyphosphate (TPP) nanoparticles loaded with flavonoids-enriched vegetable extracts (Ginkgo biloba L., Dimorphandra mollis Benth, Ruta graveolens, and Vitis vinifera L.) were produced and characterized for their morphology, mean particle size, zeta potential, and encapsulation efficiency. A final topical formulation was obtained by dispersing chitosan/TPP nanoparticles in an o/w emulsion. Results showed that nanoparticles dispersion exhibited yellowish color, spherical shape, and uniform appearance. Extract-loaded chitosan/TPP nanoparticles showed a mean particle size of 557.11 ± 3.1 nm, polydispersity index of 0.39 ± 0.27, zeta potential of + 11.54 ± 2.1 mV, and encapsulation efficiency of 75.89% of rutin. The recorded texture parameters confirm that the developed formulation is appropriate for skin application. The SPF obtained was 2.3 ± 0.4, with a critical wavelength of 387.0 nm and 0.69 UVA/UVB ratio. The developed formulation exhibited photostability, allowing the release of flavonoids from nanoparticles while retaining rutin into the skin in a higher extension.

Synthesis, antiproliferative activity and molecular properties predictions of galloyl derivatives.

The present study was designed to investigate the in vitro antiproliferative activity against ten human cancer cell lines of a series of galloyl derivatives bearing substituted-1,3,4-oxadiazole and carbohydrazide moieties. The compounds were also assessed in an in silico study of the absorption, distribution, metabolism and excretion (ADME) in the human body using Lipinski's parameters, the topological polar surface area (TPSA) and percentage of absorption (%ABS). In general, the introduction of N'-(substituted)-arylidene galloyl hydrazides 4-8 showed a moderate antitumor activity, while the 2-methylthio- and 2-thioxo-1,3,4-oxadiazol-5-yl derivatives 9 and 10 led to increased inhibition of cancer cell proliferation. The precursor compound methyl gallate 2 and the intermediary galloyl hydrazide 3 showed greater antiproliferative activity with GI50 values < 5.54 µM against all human tumor cell lines tested. A higher inhibition effect against ovarian cancer (OVCAR-3) (GI50 = 0.05-5.98 µM) was also shown, with compounds 2, 3, 9 and 10 with GI50 ≤ 0.89 µM standing out in this respect. The in silico study revealed that the compounds showed good intestinal absorption.

Synthesis and antitumor activity of novel 1-substituted phenyl 3-(2-oxo-1,3,4-oxadiazol-5-yl) ß-carbolines and their Mannich bases.

A series of novel 1-(substituted phenyl)-3-(2-oxo-1,3,4-oxadiazol-5-yl) ß-carbolines (4a-e) and the corresponding Mannich bases 5-9(a-c) were synthesized and evaluated for their in vitro antitumor activity against seven human cancer cell lines. Compounds of 4a-e series showed a broad spectrum of antitumor activity, with GI50 values lower than 15µM for five cell lines. The derivative 4b, having the N,N-dimethylaminophenyl group at C-1, displayed the highest activity with GI50 in the range of 0.67-3.20µM. A high selectivity and potent activity were observed for some Mannich bases, particularly towards resistant ovarian (NCI-ADR/RES) cell lines (5a, 5b, 6a, 6c and 9b), and ovarian (OVCAR-03) cell lines (5b, 6a, 6c, 9a, 9b and 9c). In addition, the interaction of compound 4b with DNA was investigated by using UV and fluorescence spectroscopic analysis. These studies indicated that 4b interact with ctDNA by intercalation binding.

Anthelmintic activity of Artemisia annua L. extracts in vitro and the effect of an aqueous extract and artemisinin in sheep naturally infected with gastrointestinal nematodes.

There is no effective natural alternative control for gastrointestinal nematodes (GIN) of small ruminants, with Haemonchus contortus being the most economically important GIN. Despite frequent reports of multidrug-resistant GIN, there is no new commercial anthelmintic to substitute failing ones. Although trematocidal activity of artemisinin analogs has been reported in sheep, neither artemisinin nor its plant source (Artemisia annua) has been evaluated for anthelmintic activity in ruminants. This study evaluated the anthelmintic activity of A. annua crude extracts in vitro and compared the most effective extract with artemisinin in sheep naturally infected with H. contortus. A. annua leaves extracted with water, aqueous 0.1% sodium bicarbonate, dichloromethane, and ethanol were evaluated in vitro by the egg hatch test (EHT) and with the bicarbonate extract only for the larval development test (LDT) using H. contortus. The A. annua water, sodium bicarbonate (SBE), ethanol, and dichloromethane extracts tested in vitro contained 0.3, 0.6, 4.4, and 9.8% of artemisinin, respectively. The sodium bicarbonate extract resulted in the lowest LC99 in the EHT (1.27 µg/mL) and in a LC99 of 23.8 µg/mL in the LDT. Following in vitro results, the SBE (2 g/kg body weight (BW)) and artemisinin (100 mg/kg BW) were evaluated as a single oral dose in naturally infected Santa Inês sheep. Speciation from stool cultures established that 84-91% of GIN were H. contortus, 8.4-15.6 % were Trichostrongylus sp., and 0.3-0.7% were Oesophagostomum sp. Packed-cell volume and eggs per gram (EPG) of feces were used to test treatment efficacy. The SBE tested in vivo contained no artemisinin, but had a high antioxidant capacity of 2,295 µmol of Trolox equivalents/g. Sheep dosed with artemisinin had maximum feces concentrations 24 h after treatment (126.5 µg/g artemisinin), which sharply decreased at 36 h. By day 15, only levamisole-treated sheep had a significant decrease of 97% in EPG. Artemisinin-treated and SBE-treated sheep had nonsignificant EPG reductions of 28 and 19%, respectively, while sheep in infected/untreated group had an average EPG increase of 95%. Sheep treated with artemisinin and A. annua SBE maintained blood hematocrits throughout the experiment, while untreated/infected controls had a significant reduction in hematocrit. This is the first time oral dose of artemisinin and an aqueous extract of A. annua are evaluated as anthelmintic in sheep. Although oral dose of artemisinin and SBE, at single doses, were ineffective natural anthelmintics, artemisinin analogs with better bioavailability than artemisinin should be tested in vivo, through different routes and in multiple doses. The maintenance of hematocrit provided by artemisinin and A. annua extract and the high antioxidant capacity of the latter suggest that they could be combined with commercial anthelmintics to improve the well-being of infected animals and to evaluate potential synergism.

Evaluation of the cytotoxicity and phototoxicity of Caryocar brasiliense supercritical carbon dioxide extract.

BACKGROUND: Caryocar brasiliense Camb (Pequi) is a typical Brazilian Cerrado fruit tree. Its fruit is used as a vitamin source for culinary purposes and as a source of oil for the manufacture of cosmetics. C. brasiliense supercritical CO2 extracts exhibit antimicrobial activity against the bacteria Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and also possess antioxidant activity. This study was designed to evaluate the in vitro cytotoxicity and phototoxicity of the supercritical CO2 extract obtained from the leaves of this species. METHODS: In vitro cytotoxicity and phototoxicity of C. brasiliense supercritical CO2 extracts were assessed using a tetrazolium-based colorimetric assay (XTT) and Neutral Red methods. RESULTS: We found that the C. brasiliense (Pequi) extract obtained by supercritical CO2 extraction did not present cytotoxic and phototoxic hazards. CONCLUSIONS: This finding suggests that the extract may be useful for the development of cosmetic and/or pharmaceutical products.

Caryocar brasiliense supercritical CO2 extract possesses antimicrobial and antioxidant properties useful for personal care products.

BACKGROUND: The cosmetic and pharmaceutical industries have an increasing interest in replacing synthetic antimicrobials in dermatological products due to increased microbial resistance to conventional antimicrobial agents. Pequi (Caryocar brasiliense) is a native fruit tree of the Brazilian Cerrado, specifically used in cosmetics, in the food industry, and for medicinal purposes. Leishmanicidal and antifungal activities have been reported previously. This study was designed to evaluate the antimicrobial and antioxidant activities of a C. brasiliense extract obtained by supercritical CO2 extraction. METHODS: The minimum inhibitory concentrations (MICs) against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were determined by the classical microdilution method. Antiseptic activity against these organisms was evaluated by the plate diffusion method. The antioxidant potential of the extract was evaluated using a method based on the oxidation of 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS). The extract's chemical profile was analyzed for the presence of alkaloids, saponins, anthraquinones, steroids, tannins, flavonoids, and phenolic compounds according to standard colorimetric methods. RESULTS: The C. brasiliense supercritical CO2 extract exhibits antimicrobial activity against all bacteria tested. It also possesses antioxidant activity, when compared to a vitamin E standard. CONCLUSIONS: The C. brasiliense supercritical CO2 extract may be useful for the development of personal care products, primarily for antiseptic skin products that inactivate, reduce, prevent, or arrest the growth of microorganisms with the inherent intent to mitigate or prevent disease as well as products that minimize damage caused by free radicals.

ß-Carboline derivatives are potent against Acute Myeloid Leukemia in vitro and in vivo.

BACKGROUND: ß-carboline alkaloids exert a distinguished ability to impair cell growth and induce cell death in a variety of cancers and the evaluation of such new therapeutic candidates may denote new possibilities for leukemia treatment. In this present study, we screened 12 ß-carboline derivatives containing different substituents at 1- and 3-positions of ß-carboline nucleus for their antineoplastic activities in a panel of leukemia cell lines. METHODS: The cytotoxic effects of the ß-carboline derivatives were evaluated in different leukemia cell lines as well as reactive oxygen species (ROS) generation, autophagy, and important signaling pathways. RESULTS: Treatment with the ß-carboline derivatives resulted in a potent antineoplastic activity leading to a reduced cell viability that was associated with increased cell death in a concentration-dependent manner. Interestingly, the treatment of primary mononuclear cells isolated from the peripheral blood of healthy donors with the ß-carboline derivatives showed a minor change in cell survival. The antineoplastic activity occurs by blocking ROS production causing consequent interruption of the PI3K/AKT and MAPK/ERK signaling and modulating autophagy processes. Notably, in vivo, AML burden was diminished in peripheral blood and bone marrow of a xenograft mouse model. CONCLUSIONS: Our results indicated that ß-carboline derivatives have an on-target malignant cell-killing activity and may be promising candidates for treating leukemia cells by disrupting crucial events that promote leukemia expansion and chemotherapy resistance.

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

BACKGROUND: Annona 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. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: Our 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.

Cytoprotective effect of Fridericia chica (Bonpl.) L.G. Lohmann extract associated with geranylgeraniol enriched-fraction from Bixa orellana L. on epithelial cells treated with bisphosphonate.

Bisphosphonates are drugs used to treat bone disorders. The chronic use of bisphosphonates is associated with the occurrence of medication-related osteonecrosis of the jaw (MRONJ). Previous data reported the positive effects of Geranylgeraniol on different cell types treated with Bisphosphonates. Foregoing work done by our research group demonstrated the wound healing capacity of Fridericia chica (Bonpl.) L.G.Lohmann standardized ethanol extract. Herein in vitro cytoprotective synergistic effect of the association of F. chica extract associated with an enriched geranylgeraniol fraction on keratinocytes exposed to zoledronic acid is reported. An association of F. chica at 1 and 5 µg/mL with geranylgeraniol at 15 µg/mL, increased cell viability by 73.5% and 71.1%, respectively. This treatment did not increase tumor cells viability; whereas the clonogenic potential assessment showed that, the association with F. chica (5 µg/mL) reversed the effects of zoledronic acid on the cells. This study provides data for a potential treatment for MRONJ.

Protective effect of topical Cordia verbenacea in a rat periodontitis model: immune-inflammatory, antibacterial and morphometric assays.

BACKGROUND: This study evaluated the effects of C. verbenacea essential oil topically administered in a rat periodontitis model. METHODS: Periodontitis was induced on rats in one of the mandibular first molars assigned to receive a ligature. Animals were randomly divided into two groups: a) non-treatment group (NT) (n = 18): animals received 1mL of vehicle; b) C. verbenacea group (C.v.) (n = 18): animals received 5mg/Kg of essential oils isolated from C. verbenacea. The therapies were administered topically 3 times daily for 11 days. Then, the specimens were processed for morphometric analysis of bone loss. The ligatures were used for microbiological assessment of the presence of Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Porphyromonas gingivalis using PCR. The gingival tissue was collected to Elisa assay of interleukin (IL)-1α and IL-10 levels. RESULTS: Bone loss was inhibited by C. verbenacea when compared to the NT group (p < 0.05). A decrease in the levels of IL-1α and increase in the IL-10 amounts was observed in the C.v. group as compared to NT group (p < 0.05). A lower frequency of P. gingivalis was found in C.v. group (p < 0.05). CONCLUSION: C. verbenacea essential oil topically administered diminished alveolar bone resorption, promoting a positive local imbalance in the pro/anti-inflammatory system and reducing the frequency of detection of P. gingivalis.

Synthesis, antitumor, antitrypanosomal and antileishmanial activities of benzo[4,5]canthin-6-ones bearing the N'-(Substituted benzylidene)-carbohydrazide and N-Alkylcarboxamide groups at C-2.

A series of novel benzo[4,5]canthin-6-ones, bearing the N'-(substituted benzylidene)-carbohydrazide (11a-e) and N-alkylcarboxamide (13a-g) moieties at position-2, were synthesized and screened for their in vitro antitumor activity, against seven human cancer cell lines, and for antitrypanosomal and antileishmanial activities against Trypanosoma cruzi and Leishmania amazonensis. The results indicated that N-methylpiperazyl-6-oxobenzo[4,5]canthine-2-carboxamide (13f) displayed potent antitumor activity with IC(50) values in the range of 1.15-8.46 µM for all cell lines tested. Compounds 13f and 13g bearing an N-methylpiperazylcarboxamide and N-morpholylcarboxamide at C-2, respectively, showed potent activities towards both Trypanosoma cruzi and Leishmania amazonensis parasites, with IC(50) in the range of 0.4 to 16.70 µM.