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1.
Braz J Microbiol ; 54(3): 1501-1511, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37338788

ABSTRACT

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as blisters/ulcers. However, severe conditions such as keratitis, encephalitis, and systemic infections may occur, generally associated with the patient's immunological condition. Although Acyclovir® (ACV) and its analogs are the reference drugs for herpetic infections, the number of ACV-resistant HSV infections is growing exponentially. Therefore, new natural products' bioactive compounds have been studied to develop novel effective anti-herpetics. Trichilia catigua is a plant widely used in traditional medicine, including the treatment of skin diseases and sexual infections. In our study, 16 extracts from the bark of T. catigua, obtained with different solvents and their combinations, were evaluated against HSV-1 AR and HSV-2, respectively, ACV resistance and genital strains in vitro. The extracts with the highest selectivity index were used to prepare new topical anti-herpetic formulations and confirmed in vivo. Two new topical formulations were suggested to treat cutaneous and genital herpetic recurrent lesions. The cytotoxicity and antiviral activity were tested using the MTT method. The cytotoxic (CC50) and inhibitory (IC50) concentrations of 50% and the selectivity index (SI: CC50/IC50) were determined. Tc12, Tc13, and Tc16 were added to the formulations. Infected BALB/c mice were treated for 8 days, and the severity of the herpetic lesions was analyzed daily. All CEs showed a CC50 value ranging from 143 to 400 µg/mL, except for Tc3 and Tc10. Tc12, Tc13, and Tc16 showed the best SI in the 0 h, virucidal, and adsorption inhibition assays. In the in vivo test against HSV-1 AR, the infected animals treated with creams were statistically different from the infected non-treated animals and similar to ACV-treated mice. In HSV-2-infected genitalia, similar effects were found for Tc13 and Tc16 gels. The present study demonstrated that extracts from the bark of T. catigua, traditionally used in folk medicine, are a valuable source of active compounds with anti-herpetic activity. The extracts showed a virucidal mechanism of action and prevented the initial stages of viral replication. The cutaneous and genital infections were strongly inhibited by the Tc12, Tc13, and Tc16 extracts. New topical therapeutic alternatives using Trichilia catigua extracts are suggested for patients infected with ACV-resistant strains of HSV.


Subject(s)
Herpes Simplex , Herpesvirus 1, Human , Meliaceae , Mice , Animals , Acyclovir/pharmacology , Acyclovir/therapeutic use , Reinfection , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Herpes Simplex/drug therapy , Herpesvirus 2, Human/physiology , Genitalia
2.
Antibiotics (Basel) ; 12(3)2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36978378

ABSTRACT

Life-threatening Candida infections have increased with the COVID-19 pandemic, and the already limited arsenal of antifungal drugs has become even more restricted due to its side effects associated with complications after SARS-CoV-2 infection. Drug combination strategies have the potential to reduce the risk of side effects without loss of therapeutic efficacy. The aim of this study was to evaluate the combination of ent-hardwickiic acid with low concentrations of amphotericin B against Candida strains. The minimum inhibitory concentration (MIC) values were determined for amphotericin B and ent-hardwickiic acid as isolated compounds and for 77 combinations of amphotericin B and ent-hardwickiic acid concentrations that were assessed by using the checkerboard microdilution method. Time-kill assays were performed in order to assess the fungistatic or fungicidal nature of the different combinations. The strategy of combining both compounds markedly reduced the MIC values from 16 µg/mL to 1 µg/mL of amphotericin B and from 12.5 µg/mL to 6.25 µg/mL of ent-hardwickiic acid, from isolated to combined, against C. albicans resistant to azoles. The combination of 1 µg/mL of amphotericin B with 6.25 µg/mL of ent-hardwickiic acid killed all the cells of the same strain within four hours of incubation.

3.
J Insect Sci ; 19(6)2019 Nov 01.
Article in English | MEDLINE | ID: mdl-31841603

ABSTRACT

Spodoptera frugiperda (J. E. Smith) is one of the major pests of maize in Argentina. The main tool for its control is the use of genetically modified maize hybrids expressing Bacillus thuringiensis (Bt) insecticidal proteins. Maize growers in Argentina initially controlled this pest with Bt maize that expressed a single Bt protein (Cry1Ab or Cry1F). Currently it is necessary to plant maize cultivars that produce two Bt proteins to achieve the satisfactory control. Recently, Cry1F field-evolved resistant populations of this species were confirmed in Argentina. The objective of this study was to evaluate the performance of S. frugiperda field-collected strains on different Bt and non-Bt maize hybrids. Strains were collected from non-Bt maize (T1), Agrisure TDMax (T2), Agrisure Viptera (T3), Agrisure Viptera 3110 (T4), Genuity VT Triple Pro (T5), and Power Core (T6). Three experiments were performed to 1) determine the survivorship and reproduction of field-collected larvae (F0) from Bt maize hybrids, 2) evaluate Cry1F resistance using an F1 screen, and 3) assess the performance of F1 strains on different maize hybrids. In the F0, the survivorship from larva to adult ranged from 0 to 63%. We obtained adults from only the T1, T2, T5, and T6 strains with no significant differences in the reproductive parameters. Continuously rearing F1 larvae on their collected hosts affected larval duration, which was significantly shorter for a known-laboratory Bt-susceptible strain than the field-collected strains. Our results support the existence of Cry1F-resistance alleles in S. frugiperda field populations in Argentina.


Subject(s)
Bacterial Proteins , Endotoxins , Hemolysin Proteins , Spodoptera , Animals , Bacillus thuringiensis Toxins , Female , Insecticide Resistance/genetics , Male , Plants, Genetically Modified , Zea mays
4.
Fitoterapia ; 136: 104179, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31121252

ABSTRACT

Essential oils, mixtures of volatile compounds, are targets of research for new antimicrobial drugs. In order to verify the potential from species of the Nectandra genus, the present study evaluated the essential oils from Nectandra amazonum, Nectandra cuspidata, Nectandra gardineri, Nectandra hihua and Nectandra megapotamica to prospect samples with high concentration of a component and its antibacterial, antibiofilm and anti-Trichomonas vaginalis activities. The essential oils from the leaves and barks were extracted by steam distillation and analyzed by gas chromatography coupled to mass spectrometry (GC-MS). The concentrations of 10 and 100 µg/mL of the essential oil were evaluated and the inhibition of bacterial growth and biofilm formation were measured, while for the evaluation of anti-T. vaginalis trophozoite viability, the concentrations from 7.8 to 1000 µg/mL were tested. Seventy-three compounds were identified from essential oils, highlighted bicyclogermacrene (up to 49.9%), elemicin (up to 42.4%), intermedeol (up to 58.2%), (E)-asarone (up to 45.9%) and (+)-α-bisabolol (up to 93.7%). The essential oil from N. megapotamica leaves presented 93.7% of (+)-α-bisabolol and demonstrated the high capacity of inhibition of the biofilm formation, in particular, against Staphylococcus aureus methicillin resistant (MRSA) and Pseudomonas aeruginosa. This sample also had significant activity against T. vaginalis (IC50 of 98.7 µg/mL) and demonstrated cytotoxic and hemolytic effects in Vero cells and human erythrocytes. In general, the Nectandra genus revealed high chemical variability and a N. megapotamica specimen accumulated a compound on high concentration with great potential for biotechnological exploration as a new antibiofilm and anti-T. vaginalis.


Subject(s)
Anti-Bacterial Agents/pharmacology , Biofilms/drug effects , Lauraceae/chemistry , Oils, Volatile/pharmacology , Sesquiterpenes/pharmacology , Trichomonas vaginalis/drug effects , Animals , Antiprotozoal Agents/pharmacology , Brazil , Chlorocebus aethiops , Erythrocytes/drug effects , Humans , Monocyclic Sesquiterpenes , Phytochemicals/pharmacology , Plant Bark/chemistry , Plant Leaves/chemistry , Vero Cells
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