In vitro, in vivo and in silico analysis of the anticancer and estrogen-like activity of guava leaf extracts.

Anticancer drug research based on natural compounds enabled the discovery of many drugs currently used in cancer therapy. Here, we report the in vitro, in vivo and in silico anticancer and estrogen-like activity of Psidium guajava L. (guava) extracts and enriched mixture containing the meroterpenes guajadial, psidial A and psiguadial A and B. All samples were evaluated in vitro for anticancer activity against nine human cancer lines: K562 (leukemia), MCF7 (breast), NCI/ADR-RES (resistant ovarian cancer), NCI-H460 (lung), UACC-62 (melanoma), PC-3 (prostate), HT-29 (colon), OVCAR-3 (ovarian) and 786-0 (kidney). Psidium guajava's active compounds displayed similar physicochemical properties to estradiol and tamoxifen, as in silico molecular docking studies demonstrated that they fit into the estrogen receptors (ERs). The meroterpene-enriched fraction was also evaluated in vivo in a Solid Ehrlich murine breast adenocarcinoma model, and showed to be highly effective in inhibiting tumor growth, also demonstrating uterus increase in comparison to negative controls. The ability of guajadial, psidial A and psiguadials A and B to reduce tumor growth and stimulate uterus proliferation, as well as their in silico docking similarity to tamoxifen, suggest that these compounds may act as Selective Estrogen Receptors Modulators (SERMs), therefore holding significant potential for anticancer therapy.

Chemical composition and antimicrobial activity of the essential oil from the leaves and flowers of Aloysia gratissima / Composição química e atividade antimicrobiana do óleo essencial de folhas e flores de Aloysia gratissima

Volatile oils from leaves and flowers of Aloysia gratissima were investigated for their chemical composition and antimicrobial activity against the bacteria Bacilus subtilis, Staphylococcus aureus, Salmonella choleraesuis, Pseudomonas aeruginosa, Streptococcus pneumoniae and the Candida albicans yeast. The minimum inhibitory concentrations (MIC) of the oils were determined by the micro-dilution method, while the chemical composition was determined by GC-MS (gas chromatography mass spectrometry). The fresh leaves and inflorescence were subjected to hydrodistillation for 120 min using a Clevenger-type apparatus, and the essential oil was tested against microorganisms. High concentrations of sesquiterpenes were observed for the inflorescence, and monoterpenes were observed for the leaves. The main compounds of the inflorescence essential oil were E-caryophyllene, germacrene B, guaiol and bulnesol, while in the leaves the main compounds were trans-pinocamphone, trans-pinocarveyl acetate, and guaiol. The essential oil from the leaves showed an effect against P. aeruginosa and S. pneumonia, and the essential oil of the inflorescence showed an effect against P. aeruginosa, S. pneumonia, and Candida albicans.

O óleo essencial de folhas e de flores de Aloysia gratissima foi avaliado quanto à composição química e ação antimicrobiana contra as bactérias Bacilus subtilis, Staphylococcus aureus, Salmonella choleraesuis, Pseudomonas aeruginosa, Streptococcus pneumoniae, e a levedura Candida albicans. A concentração mínima inibitória (MIC) dos óleos essenciais foi determinada pelo método da microdiluição e a composição química determinada por CG-EM (Cromatografia Gasosa acoplada a Espectrômetro de Massas). Folhas e inflorescências frescas foram hidrodestiladas por 120 minutos em aparelho Clevenger sendo o óleo essencial testado contra microorganismos. Para as flores foi observada maior concentração de sesquiterpenos, enquanto que as folhas apresentaram maior concentração de monoterpenos. Os principais constituintes do óleo essencial da flor foram: E-cariofileno, germacreno B, guaiol e bulnesol; e das folhas foram: trans-pinocamfona, acetato de trans-pinocarveol e guaiol. O óleo essencial da folha mostrou atividade contra P. aeruginosa e S. pneumoniae, e o óleo essencial da flor mostrou atividade contra P. aeruginosa, S. pneumoniae e Candida albicans.

Effects of undecylenic acid released from denture liner on Candida biofilms.

Denture liners (DL) are easily colonized by Candida spp. In an attempt to prevent biofilm colonization, manufacturers have incorporated undecylenic acid (UDA) into DL. In this in vitro study, the effects of UDA released from DL on Candida biofilms were investigated. The concentrations of UDA released from commercial DL were determined by gas chromatography-mass spectrometry (GC-MS). Minimum inhibitory concentration (MIC) and minimum fungistatic concentration (MFC) tests were performed for C. albicans or C. glabrata, with UDA for comparison with the concentrations released from DL. Specimens of DL with (experimental group) and without UDA (control group) were fabricated, and Candida biofilms were developed on DL surfaces. Biofilms were evaluated by cell counts, metabolic activity, structure, and secretion of proteinase or phospholipase. The concentrations of UDA released were within the MIC and MFC ranges. In the presence of UDA, C. albicans biofilms were thinner and had lower numbers of viable and active cells, although no significant enzymatic changes were observed relative to the control group (p > 0.05). In contrast, C. glabrata biofilms exhibited higher cell counts and greater metabolic activity and also increased proteinase activity in the presence of UDA relative to the control group (p < 0.05). Overall, UDA did not prevent Candida biofilm formation.

Methyl jasmonate increases the tropane alkaloid scopolamine and reduces natural herbivory in Brugmansia suaveolens: is scopolamine responsible for plant resistance?

The tropane alkaloid (TA) scopolamine is suggested to protect Brugmansia suaveolens (Solanaceae) against herbivorous insects. To test this prediction in a natural environment, scopolamine was induced by methyl jasmonate (MJ) in potted plants which were left 10 days in the field. MJ-treated plants increased their scopolamine concentration in leaves and herbivory decreased. These findings suggest a cause-effect relationship. However, experiments in laboratory showed that scopolamine affect differently the performance of the specialist larvae of the ithomiine butterfly Placidina euryanassa (C. Felder & R. Felder) and the generalist fall armyworm Spodoptera frugiperda (J. E. Smith): the specialist that sequester this TA from B. suaveolens leaves was not negatively affected, but the generalist was. Therefore, scopolamine probably acts only against insects that are not adapted to TAs. Other compounds that are MJ elicited may also play a role in plant resistance against herbivory by generalist and specialist insects, and deserve future investigations.

Action of Coriandrum sativum L. Essential Oil upon Oral Candida albicans Biofilm Formation.

The efficacy of extracts and essential oils from Allium tuberosum, Coriandrum sativum, Cymbopogon martini, Cymbopogon winterianus, and Santolina chamaecyparissus was evaluated against Candida spp. isolates from the oral cavity of patients with periodontal disease. The most active oil was fractionated and tested against C. albicans biofilm formation. The oils were obtained by water-distillation and the extracts were prepared with macerated dried plant material. The Minimal Inhibitory Concentration-MIC was determined by the microdilution method. Chemical characterization of oil constituents was performed using Gas Chromatography and Mass Spectrometry (GC-MS). C. sativum activity oil upon cell and biofilm morphology was evaluated by Scanning Electron Microscopy (SEM). The best activities against planktonic Candida spp. were observed for the essential oil and the grouped F(8-10) fractions from C. sativum. The crude oil also affected the biofilm formation in C. albicans causing a decrease in the biofilm growth. Chemical analysis of the F(8-10) fractions detected as major active compounds, 2-hexen-1-ol, 3-hexen-1-ol and cyclodecane. Standards of these compounds tested grouped provided a stronger activity than the oil suggesting a synergistic action from the major oil constituents. The activity of C. sativum oil demonstrates its potential for a new natural antifungal formulation.

Antimicrobial activity of garlic against oral streptococci.

The antimicrobial activity of two garlic clones' (1: purple and 2: white) crude extracts against oral microbiota was evaluated in vitro (study 1) and in vivo (study 2). Study 1 consisted of the evaluation of minimum inhibitory (MIC) and bactericidal (MBC) concentrations against nine streptococci strains. In study 2, a 2.5% garlic (clone 2) solution was used as a mouthwash in a 5-week study by 30 subjects. Blood agar and Mitis Salivarius Bacitracin agar were inoculated with subjects' saliva to quantify oral microorganisms and mutans streptococci. Study 1 showed MIC ranging from 0.5 to 32.0 mg ml(-1) for clone 2 and from 8 to 64.0 mg ml(-1) for clone 1. MBC ranged from 1.0 to 128.0 mg ml(-1) and from 8.0 to 128.0 mg ml(-1) regarding clones 2 and 1 respectively. Study 2 showed that 2.5% garlic mouthwash solution had good antimicrobial activity against mutans streptococci and oral microorganisms. Maintenance of reduced salivary levels of streptococci was observed after 2 weeks at the end of mouthwash use. Unpleasant taste (100%), halitosis (90%) and nausea (30%) were reported by subjects after the end of the study. It was concluded that the garlic clones have antimicrobial properties in vitro against streptococci and anticariogenic properties against oral microorganism in spite of its adverse effects.

Antimicrobial activity of garlic, tea tree oil, and chlorhexidine against oral microorganisms.

OBJECTIVE: To compare the antimicrobial activity of tea tree oil, garlic, and chlorhexidine solutions against oral microorganisms. METHOD: The five-week study consisted of thirty subjects. The first week was considered baseline. All subjects used a control solution (second week), and were randomly divided into the three groups (third week): G1-0.12% chlorhexidine; G2 - 2.5% garlic (Allium sativum, L.); and G3 - 0.2% tea tree oil (Melaleuca alternifolia). Dishes containing blood agar and Mitis Salivarius Bacitracin agar (MSB) were inoculated with the subjects' saliva (collected twice a week). Total microorganisms and mutans streptococci were counted in blood agar and MSB, respectively. RESULTS: Chlorhexidine and garlic groups showed antimicrobial activity against mutans streptococci, but not against other oral microorganisms. The tea tree oil group showed antimicrobial activity against mutans streptococci and other oral microorganisms. Maintenance of reduced levels of microorganisms was observed only for garlic and tea tree oil during the two consecutive weeks (fourth and fifth). Unpleasant taste (chlorhexidine 40%, tea tree oil 30%, garlic 100%), burning sensation (chlorhexidine 40%, tea tree oil 60%, garlic 100%), bad breath (chlorhexidine 40%, tea tree oil 20%, garlic 90%), and nausea (chlorhexidine 0%, tea tree oil 10%, garlic 30%) were reported. CONCLUSION: Garlic and tea tree oil might be an alternative to chlorhexidine.