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1.
J Chem Ecol ; 51(1): 11, 2025 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-39862331

RESUMO

The small black stem bug, Paratibraca (= Glyphepomis) spinosa (Campos and Grazia 1998), is a rice pest in Brazil and is part of a complex of stink bugs that includes Oebalus poecilus (Dallas) and Tibraca limbativentris Stål. Together, these pentatomid species pose a serious threat to rice crops throughout South America. In this study, we identified the sex pheromone of P. spinosa. Our findings revealed that male P. spinosa produces four male-specific compounds identical to those produced by T. limbativentris males. These include (3S,6S,7R)-1,10-bisaboladien-3-ol and (3R,6S,7R)-1,10-bisaboladien-3-ol (zingiberenols), both sharing the same absolute configuration as the 1,10-bisaboladien-3-ol from T. limbativentris; along with two minor male-specific components: the cis and trans isomers of 2,10-bisaboladien-1-ol (sesquipiperitol). Y-tube olfactometer bioassays demonstrated that P. spinosa females were attracted to the odours of live males, whereas males showed no attraction to either sex. Females were particularly drawn to male volatiles, especially the fraction containing the compounds 1,10-bisaboladien-3-ol and 2,10-bisaboladien-1-ol. When tested with synthetic compounds, females were attracted to a blend of the two isomers, (3S,6S,7R)-1,10-bisaboladien-3-ol and (3R,6S,7R)-1,10-bisaboladien-3-ol, in the same ratio as naturally produced by males. Given that the sex pheromone compounds identified in P. spinosa are identical to those of T. limbativentris, we conducted bioassays with live heterospecific insects. In olfactometer bioassays, the females of both species were attracted by the odours of heteroespecific males.


Assuntos
Sesquiterpenos , Atrativos Sexuais , Masculino , Animais , Atrativos Sexuais/farmacologia , Atrativos Sexuais/química , Atrativos Sexuais/metabolismo , Feminino , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Sesquiterpenos/análise , Heterópteros/química , Heterópteros/fisiologia , Heterópteros/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Sesquiterpenos Monocíclicos/metabolismo , Sesquiterpenos Monocíclicos/química , Oryza/química , Feromônios/química , Feromônios/metabolismo
2.
Food Res Int ; 201: 115548, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39849702

RESUMO

Baru (Dipteryx alata Vogel), a fruit native to the Brazilian Cerrado, has gained scientific interest due to its nutritional potential and commercial value. Its edible seed, of high commercial value, represents around 5 % of the fruit. On the other hand, its pulp, a byproduct of the baru processing industry, is normally discarded, generating a huge volume of waste with reported antioxidant properties. This study investigates the composition and bioactive properties of baru pulp, aiming to identify the antioxidant components in this byproduct. Our analysis revealed that baru pulp is rich in sugars (41.86 %), fiber (29.12 %), and essential minerals, along with commercially valuable bioactive compounds such as trigonelline (139.10 mg 100 g-1), tannins (429.16 mg tannin equivalent 100 g-1), vitamin C (109.57 mg 100 g-1), and phenolic compounds such as trans-cinnamic acid (5.91 mg 100 g-1), chlorogenic acid, and gallic acid (1.07 mg 100 g-1). Industrially relevant sesquiterpenes, such as α-copaene and bicyclogermacrene, account for 42.75 % of the volatile profile, alongside germacrene D (11.69 %), aromadendrene (9.05 %), α-cubebene (6.84 %), ß-elemene (5.90 %), and ledene (5.82 %), which are commonly used in essential oil production from other food matrices. While further studies are required to optimize extraction methods, these findings highlight baru pulp as a promising and low-cost alternative to traditional sources of bioactive compounds, with potential applications in functional food formulations and sustainable industrial processes. Specifically, the use of in natura pulp or its flour for food enrichment is recommended, supporting sustainability through the valorization of agro-industrial waste.


Assuntos
Antioxidantes , Dipteryx , Frutas , Frutas/química , Antioxidantes/análise , Dipteryx/química , Fenóis/análise , Extratos Vegetais/química , Extratos Vegetais/análise , Brasil , Taninos/análise , Resíduos Industriais/análise , Sesquiterpenos/análise
3.
Molecules ; 30(2)2025 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-39860137

RESUMO

In the present study, the hexane extract from branches of Drimys brasiliensis (Winteraceae) displayed potent activity against Schistosoma mansoni parasites (100% mortality of the worms at 200 µg/mL). Bioactivity-guided fractionation afforded, in addition to the previously reported bioactive sesquiterpene 3,6-epidioxy-bisabola-1,10-diene, two chemically related drimane sesquiterpenes-polygodial (1) and 9-deoxymuzigadial (2). The anti-S. mansoni effects for compounds 1 and 2 were determined in vitro, with compound 1 demonstrating significant potency (EC50 value of 10 µM for both male and female worms), while 2 was inactive. Cytotoxicity assays against Vero cells revealed no toxicity for either compound (CC50 > 200 µM). Additionally, an in silico analysis was conducted using the SwissADME platform for 1, revealing that this natural sesquiterpene exhibited adherence to several ADME parameters and no PAINS violations. Finally, in vivo studies with S. mansoni-infected mice treated with compound 1 demonstrated a 44.0% reduction in worm burden, accompanied by decreases in egg production of 71.8% in feces and 69.5% in intestines. These findings highlight the potential of polygodial (1) as a promising prototype for schistosomiasis treatment.


Assuntos
Drimys , Extratos Vegetais , Schistosoma mansoni , Sesquiterpenos , Animais , Schistosoma mansoni/efeitos dos fármacos , Camundongos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Drimys/química , Chlorocebus aethiops , Feminino , Masculino , Células Vero , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/parasitologia , Esquistossomicidas/farmacologia , Esquistossomicidas/química , Esquistossomicidas/isolamento & purificação
4.
Sci Rep ; 15(1): 3564, 2025 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-39875401

RESUMO

The Asian Citrus Psyllid (ACP), Diaphorina citri, severely threatens citrus production worldwide by transmitting the greening (= Huanglongbing)-causing bacterium Candidatus Liberibacter asiaticus. There is growing evidence that the push-pull strategy is suitable to partially mitigate HLB by repelling ACP with transgenic plants engineered to produce repellents and attracting the vector to plants with a minimal disease transmission rate. Species that pull ACP away from commercial citrus plants have been identified, and transgenic plants that repel ACP have been developed. The concept of a repellent-producing plant was first demonstrated with an Arabidopsis line engineered to overexpress a gene controlling the synthesis of ß-caryophyllene and other sesquiterpenes. We have analyzed the volatile organic compounds released by this Arabidopsis line and identified α-humulene, α-copaene, and trace amounts of ß-elemene, in addition to ß-caryophyllene. Behavioral measurements demonstrated that α-copaene repels ACP at doses ca. 100× lower than those needed for ß-caryophyllene repellence. In contrast, α-humulene is innocuous at the level emitted by the transgenic plant. We confirmed that a mixture of the three sesquiterpenes in the ratio 1:100:10 repels ACP. Likewise, a commercial sample of copaiba oil containing the three sesquiterpenes, in a proportion similar to that in the transgenic plant, repelled ACP.


Assuntos
Citrus , Hemípteros , Repelentes de Insetos , Sesquiterpenos Policíclicos , Sesquiterpenos , Hemípteros/efeitos dos fármacos , Animais , Repelentes de Insetos/farmacologia , Citrus/parasitologia , Sesquiterpenos/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Monocíclicos/farmacologia , Plantas Geneticamente Modificadas , Doenças das Plantas/parasitologia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/microbiologia , Arabidopsis/genética , Compostos Orgânicos Voláteis/farmacologia , Compostos Orgânicos Voláteis/química
5.
Zygote ; 32(6): 446-451, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39559830

RESUMO

The secondary metabolites of several plant species, particularly sesquiterpenic lactones (SLs) have been studied by different research groups for over 30 years. This group of metabolites presents numerous biological activities such as antibacterial, antiviral, antiulcer, cell proliferation inhibitor, and oocyte activator with participation in exocytosis processes. This study aims to assess some sperm parameters in epididymal gametes of Chichilla lanigera exposed to increasing concentrations (0 to 2 mM) of DhL for various incubation times from 10 to 40 minutes. We determined the participation of different cell signalling pathways in the induced acrosome reaction. Our results showed an alteration in the progressive motility pattern and cell viability depending on DhL concentration and exposure time of gametes. When analyzing acrosomal status, higher percentages than the negative control were obtained in all tested doses. Both isolated and joint inhibition tests of PKA and phospholipases (PLC and PLA2) showed a greater participation of PI-PLC. This is the first report concerning the effects of this lactone on the medium of sperm incubation. Consequently, further studies will be necessary to determine the molecular implications of this lactone on the fertilizing potential of the sperm.


Assuntos
Reação Acrossômica , Lactonas , Sesquiterpenos , Transdução de Sinais , Motilidade dos Espermatozoides , Espermatozoides , Masculino , Animais , Reação Acrossômica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Espermatozoides/efeitos dos fármacos , Espermatozoides/fisiologia , Espermatozoides/metabolismo , Lactonas/farmacologia , Motilidade dos Espermatozoides/efeitos dos fármacos , Sesquiterpenos/farmacologia , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Fosfolipases A2/metabolismo
6.
Appl Microbiol Biotechnol ; 108(1): 462, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264460

RESUMO

Bioinformatic analysis revealed that the genomes of ubiquitous Penicillium spp. might carry dozens of biosynthetic gene clusters (BGCs), yet many clusters have remained uncharacterized. In this study, a detailed investigation of co-culture fermentation including the basidiomycete Armillaria mellea CPCC 400891 and the P. brasilianum CGMCC 3.4402 enabled the isolation of five new compounds including two bisabolene-type sesquiterpenes (arpenibisabolanes A and B), two carotane-type sesquiterpenes (arpenicarotanes A and B), and one polyketide (arpenichorismite A) along with seven known compounds. The assignments of their structures were deduced by the extensive analyses of detailed spectroscopic data, electronic circular dichroism spectra, together with delimitation of the biogenesis. Most new compounds were not detected in monocultures under the same fermentation conditions. Arpenibisabolane A represents the first example of a 6/5-fused bicyclic bisabolene. The bioassay of these five new compounds exhibited no cytotoxic activities in vitro against three human cancer cell lines (A549, MCF-7, and HepG2). Moreover, sequence alignments and bioinformatic analysis to other metabolic pathways, two BGCs including Pb-bis and Pb-car, responsible for generating sesquiterpenoids from co-culture were identified, respectively. Furthermore, based on the chemical structures and deduced gene functions of the two clusters, a hypothetic metabolic pathway for biosynthesizing induced sesquiterpenoids was proposed. These results demonstrated that the co-culture approach would facilitate bioprospecting for new metabolites even from the well-studied microbes. Our findings would provide opportunities for further understanding of the biosynthesis of intriguing sesquiterpenoids via metabolic engineering strategies. KEY POINTS: • Penicillium and Armillaria co-culture facilitates the production of diverse secondary metabolites • Arpenibisabolane A represents the first example of 6/5-fused bicyclic bisabolenes • A hypothetic metabolic pathway for biosynthesizing induced sesquiterpenoids was proposed.


Assuntos
Armillaria , Técnicas de Cocultura , Fermentação , Penicillium , Metabolismo Secundário , Sesquiterpenos , Armillaria/metabolismo , Armillaria/genética , Penicillium/metabolismo , Penicillium/genética , Penicillium/química , Sesquiterpenos/metabolismo , Sesquiterpenos/química , Humanos , Família Multigênica , Linhagem Celular Tumoral , Vias Biossintéticas/genética , Policetídeos/metabolismo , Policetídeos/química , Policetídeos/isolamento & purificação , Células Hep G2
7.
Exp Parasitol ; 265: 108808, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39094996

RESUMO

This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of L. amazonensis (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC50 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC50 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of L. amazonensis, with IC50 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against L. amazonensis promastigotes and amastigotes, being a promising system for future in vivo trials.


Assuntos
Emulsões , Macrófagos Peritoneais , Sesquiterpenos Monocíclicos , Sesquiterpenos , Pele , Animais , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Monocíclicos/química , Emulsões/química , Camundongos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Pele/parasitologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Cutânea/parasitologia , Espectroscopia de Infravermelho com Transformada de Fourier , Absorção Cutânea/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Feminino , Leishmania/efeitos dos fármacos , Tensoativos/farmacologia , Tensoativos/química , Antiprotozoários/farmacologia , Antiprotozoários/química
8.
Sci Rep ; 14(1): 18875, 2024 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143185

RESUMO

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is one of the most important neglected diseases in Latin America. The limited use of the current nitro-derivative-based chemotherapy highlights the need for alternative drugs and the identification of their molecular targets. In this study, we investigated the trypanocidal effect of the sesquiterpene lactone dehydroleucodine (DhL) and its derivatives, focusing on the antioxidative defense of the parasites. DhL and two derivatives, at lesser extent, displayed antiproliferative effect on the parasites. This effect was blocked by the reducing agent glutathione (GSH). Treated parasites exhibited increased intracellular ROS concentration and trypanothione synthetase activity, accompanied by mitochondrial swelling. Although molecular dynamics studies predicted that GSH would not interact with DhL, 1H-NMR analysis confirmed that GSH could protect parasites by interacting with the lactone. When parasites overexpressing mitochondrial tryparedoxin peroxidase were incubated with DhL, its effect was attenuated. Overexpression of cytosolic tryparedoxin peroxidase also provided some protection against DhL. These findings suggest that DhL induces oxidative imbalance in T. cruzi, offering new insights into potential drug targets against this parasite.


Assuntos
Lactonas , Espécies Reativas de Oxigênio , Sesquiterpenos , Trypanosoma cruzi , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/metabolismo , Sesquiterpenos/farmacologia , Lactonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tripanossomicidas/farmacologia , Glutationa/metabolismo , Doença de Chagas/tratamento farmacológico , Doença de Chagas/parasitologia , Proteínas de Protozoários/metabolismo , Animais , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Amida Sintases
9.
Biomed Chromatogr ; 38(9): e5949, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38956820

RESUMO

α-Bisabolol (α-BIS) is a sesquiterpene alcohol present in chamomile essential oil [Chamomilla recutita (L.) Rauschert]. Despite its numerous pharmacological effects, its pharmacokinetics remain understudied. An analytical method capable of quantifying α-BIS in plasma is crucial to enable pharmacokinetic analysis. Presently, only one study has quantified it using mass spectrometry. Administering α-BIS requires a nanoemulsion for intravenous injection. This study aimed to develop and validate a bioanalytical method using high-performance liquid chromatography with an ultraviolet detector to quantify α-BIS in rat plasma. The method employed acetonitrile and ultrapure water (80:20, v/v) as the mobile phase, with a flow rate of 1 ml/min and concentrations ranging from 465 to 29.625 µg/ml. All US Food and Drug Administration-designated assays were successful, indicating the method's precision, accuracy, sensitivity and linearity in determining α-BIS in rat plasma. The developed nanoemulsion, assessed through dynamic light scattering analysis, the ensemble collection of particles and polydispersity index evaluation, proved safe and effective for intravenous administration. The pharmacokinetic parameters such as volume of distribution, clearance and half-life indicated that α-BIS tends to persist in the body. This study provides a foundation for further research to explore α-BIS's potential pharmaceutical applications in the future.


Assuntos
Emulsões , Sesquiterpenos Monocíclicos , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ratos , Emulsões/química , Reprodutibilidade dos Testes , Sesquiterpenos Monocíclicos/farmacocinética , Sesquiterpenos Monocíclicos/sangue , Sesquiterpenos Monocíclicos/química , Masculino , Projetos Piloto , Modelos Lineares , Limite de Detecção , Sesquiterpenos/farmacocinética , Sesquiterpenos/sangue , Sesquiterpenos/química , Ratos Sprague-Dawley , Espectrofotometria Ultravioleta/métodos
10.
Microb Pathog ; 193: 106782, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38969186

RESUMO

The natural antimicrobial properties of essential oils (EOs) have contributed to the battle against multidrug-resistant microorganisms by providing new ways to develop more effective antibiotic agents. In this study, we investigated the chemical composition of Ocotea diospyrifolia essential oil (OdOE) and its antimicrobial properties combined with amikacin (AMK). Through gas chromatography-mass spectrometry (GCMS) analysis, the primary constituents of OdOE were identified as α-bisabolol (45.8 %), ß-bisabolene (9.4 %), γ-elemene (7.6 %), (Z)- ß-farnesene (5.2 %), spathulenol (3.5 %), (Z)-caryophyllene (3.3 %), and (E)-caryophyllene (3.1 %). In vitro assessments showed that the combined administration of OdOE and AMK exerted a synergistic antibacterial effect on the multidrug-resistant K. pneumoniae strain. This synergistic effect demonstrated bacteriostatic action. OdEO combined with amikacin showed protein extravasation within 2 h of treatment, leading to bacterial death, which was determined by a reduction in viable cell count. The effective concentrations showed hemocompatibility. In vivo assessments using Caenorhabditis elegans as a model showed the survival of 85 % of infected nematodes. Therefore, the combination OdEO combined with amikacin exhibited antimicrobial activity against a multidrug-resistant K. pneumoniae strain. Thus, OdOE is a promising agent that may be considered for development of antimicrobial treatment.


Assuntos
Amicacina , Antibacterianos , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Klebsiella pneumoniae , Testes de Sensibilidade Microbiana , Óleos Voláteis , Amicacina/farmacologia , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Animais , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Antibacterianos/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Cromatografia Gasosa-Espectrometria de Massas , Caenorhabditis elegans/efeitos dos fármacos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Sesquiterpenos Monocíclicos/farmacologia , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Sesquiterpenos/farmacologia
11.
J Oleo Sci ; 73(8): 1091-1104, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39085083

RESUMO

The Bauhinia ungulata, also known by its common name "pata de vaca", is one of the species used in Brazil for medicinal purposes, and is commonly used for the treatment of diabetes. In this study, the authors studied the interaction between the chemical constituents which are present in the essential oil of Bauhinia ungulata (EOBU), collected in Boa Vista-RR, Legal Amazon, and their effects on the enzyme acetylcholinesterase (AChE) in the essential oil. The analysis that we perform includes proton magnetic resonance ( 1H NMR), enzymatic inhibition, molecular docking, in silico toxicity prediction, enrichment analysis, and target prediction for biological interactions. According to the tests performed on the essential oil, it obtained 100% inhibition of the enzyme AChE. During 1H NMR experiments, it was found that α- Bisabolol, one of the main components, had a significant alteration in its chemical shift. A molecular docking analysis confirmed that this compound binds to the AChE enzyme, which confirms the 1H NMR analysis. The results of this work showed that the major component of EOBU acted as a possible inhibitor of AChE enzyme in vitro and in silico assays. These results show that EOBU could be potentially applied in Alzheimer's disease treatment.


Assuntos
Acetilcolinesterase , Bauhinia , Inibidores da Colinesterase , Simulação de Acoplamento Molecular , Óleos Voláteis , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/química , Bauhinia/química , Brasil , Acetilcolinesterase/metabolismo , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Simulação por Computador , Sesquiterpenos/farmacologia , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/química
12.
Vitam Horm ; 126: 125-168, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39029971

RESUMO

Beta-caryophyllene is an abundant terpene in cannabis, cinnamon, black pepper, cloves, and citrus fruit, delivering a striking, woody-spicy, like cloves and a sweet fruity aroma. Beta-caryophyllene is a Food and Drug Administration-approved food additive with Generally Recognized as Safe status. Interestingly, several biologic activities have been described for beta-caryophyllene, including anti-inflammatory and analgesic effects, neuroprotection against cerebral ischemia and neuronal injury, protection of neurovascular unit against oxidative damage, glial activation and neuroinflammation and anticonvulsant effects. In this chapter, we intend to review the beneficial effects of beta-caryophyllene in the context of psychiatric and neurological diseases. Also, we will analyze the possibility that the blood-brain-barrier may be a central target underlying the beneficial actions of beta-caryophyllene.


Assuntos
Barreira Hematoencefálica , Transtornos Mentais , Doenças do Sistema Nervoso , Sesquiterpenos Policíclicos , Sesquiterpenos Policíclicos/farmacologia , Humanos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Animais , Transtornos Mentais/tratamento farmacológico , Sesquiterpenos/farmacologia , Sesquiterpenos/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
13.
Planta Med ; 90(10): 792-800, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39013429

RESUMO

This work investigated interactions ascribed to the administration of phytomedicines containing Valeriana officinalis and Piper methysticum with conventional drugs. The phytomedicines were characterized by HPLC and administered per os to male Wistar rats, either concomitantly or not with the CYP3A substrate midazolam. To distinguish between the presystemic or systemic effect, midazolam was given orally and intravenously. The effects on the P-gp substrate fexofenadine uptake by Caco-2 cells were examined. The valerenic acid content was 1.6 ± 0.1 mg per tablet, whereas kavain was 13.7 ± 0.3 mg/capsule. Valerian and kava-kava extracts increased the maximum plasma concentration (Cmax) of midazolam 2- and 4-fold compared to the control, respectively. The area under the plasma concentrations versus time curve (AUC(0-∞)) was enhanced from 994.3 ± 152.3 ng.h/mL (control) to 3041 ± 398 ng.h/mL (valerian) and 4139 ± 373 ng.h/mL (kava-kava). The half-life of midazolam was not affected. These changes were attributed to the inhibition of midazolam metabolism by the enteric CYP3A since the i. v. pharmacokinetic of midazolam remained unchanged. The kava-kava extract augmented the uptake of fexofenadine by 3.5-fold compared to the control. Although Valeriana increased the uptake of fexofenadine, it was not statistically significant to that of the control (12.5 ± 3.7 ng/mg protein vs. 5.4 ± 0.3 ng/mg protein, respectively). Therefore, phytomedicines containing V. officinalis or P. methysticum inhibited the intestinal metabolism of midazolam in rats. Conversely, the P-gp-mediated transport of fexofenadine was preferably affected by kava-kava.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Citocromo P-450 CYP3A , Kava , Midazolam , Extratos Vegetais , Ratos Wistar , Terfenadina , Valeriana , Animais , Valeriana/química , Midazolam/farmacocinética , Midazolam/farmacologia , Masculino , Citocromo P-450 CYP3A/metabolismo , Citocromo P-450 CYP3A/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/efeitos dos fármacos , Terfenadina/análogos & derivados , Terfenadina/farmacocinética , Humanos , Células CACO-2 , Ratos , Kava/química , Interações Ervas-Drogas , Piper/química , Indenos , Pironas , Sesquiterpenos
14.
Rev Invest Clin ; 76(4): 173-184, 2024 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-39047236

RESUMO

Background: Hepatocellular carcinoma (HCC) is one of the most aggressive cancers worldwide. Curzerene is a sesquiterpene and component of Curcuma rhizomes and has anti-tumor and anti-inflammatory properties. Objective: The study aimed to investigate the effects of curzerene on the malignant phenotypes and tumor growth in HCC. Methods: Various concentrations of curzerene were used to treat human HCC cells (Huh7 and HCCLM3). Cell viability, apoptosis, cell cycle, invasion, and migration were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, Transwell, and wound healing assays. Cell cycle-, apoptosis-, and signaling pathway-related proteins were analyzed by Western blot analysis. A mouse xenograft model was established to analyze the anti-tumor effects of curzerene in vivo. Results: Curzerene repressed the proliferation, invasion, and migration of Huh7 and HCCLM3 cells. Curzerene also induced G2/M cycle arrest and cell apoptosis. Curzerene downregulated the CDK1, cyclin B1, PCNA, Bcl-2, matrix metallopeptidases (MMP)2, and MMP9 protein expression and upregulated the Bax, cleaved caspase3, and cleaved poly ADPribose polymerase protein expression in HCC cells. Curzerene restrained the phosphorylation of PI3K, AKT, and the Mammalian target of rapamycin (mTOR) in Huh7 and HCCLM3 cells. The in vivo data revealed that curzerene inhibited HCC tumor growth and decreased the expression of phosphorylated mTOR in xenograft mouse models. Conclusion: Curzerene inhibited cell malignancy in vitro and tumor growth in vivo in HCC, suggesting that curzerene may be a candidate agent for anti-HCC therapy.


Assuntos
Apoptose , Carcinoma Hepatocelular , Neoplasias Hepáticas , Fosfatidilinositol 3-Quinases , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Progressão da Doença , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sesquiterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Bol. latinoam. Caribe plantas med. aromát ; 23(4): 516-522, jul. 2024. graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1538029

RESUMO

This article aimed to discuss the protection of trans - nerolidol on vascular endothelial cells (ECs) injured by lipopolysac charides. ECs were divided into four groups: normal, model, low and high dose trans - nerolidol treatment groups. The cell survival rate and the contents of NO in the cell culture supernatant were determined. The protein expression and transcript level of pe roxisome proliferator - activated receptor - γ (PPARγ), endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were determined by western blotting and RT - PCR respectively. Compared with the normal group, cell livability, protein e xpression and mRNA transcript level of PPARγ and eNOS decreased, NO contents, protein expression and mRNA transcript tlevel of iNOS increased in model group significantly. Compared with model group, all the changes recovered in different degree in treatmen t groups. Hence, it was concluded that trans - nerolidol can alleviate the ECs injuryby the regulation of iNOS/eNOS through activating PPARγ in a dose - dependent manner


Este artículo tiene como objetivo discutir la protección del trans - nerolidol en las células endoteliales vasculares (CE) dañadas por lipopolisacáridos. Las CE se di vidieron en cuatro grupos: normal, modelo, grupos de tratamiento con trans - nerolidol de baja y alta dosis. Se determinó la tasa de supervivencia de las células y los contenidos de óxido nítrico (NO) en el sobrenadante del cultivo celular. La expresión de p roteínas y el nivel de transcripción del receptor activado por proliferadores de peroxisomas - γ (PPARγ), el óxido nítrico sint et asa endotelial (eNOS) y el óxido nítrico sint et asa inducible (iNOS) se determinaron mediante western blot y RT - PCR, respectivamen te. En comparación con el grupo normal, la viabilidad celular, la expresión de proteínas y el nivel de transcripción de PPARγ y eNOS disminuyeron, los contenidos de NO, la expresión de proteínas y el nivel de transcripción de iNOS aumentaron significativam ente en el grupo modelo. En comparación con el grupo modelo, todos los cambios se recuperaron en diferentes grados en los grupos de tratamiento. Por lo tanto, se concluyó que el trans - nerolidol puede aliviar el daño en las CE regulando iNOS/eNOS a través d e la activación de PPARγ de manera dependiente de la dosis.


Assuntos
Sesquiterpenos/administração & dosagem , Doenças Vasculares/tratamento farmacológico , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/lesões , Sobrevivência Celular , Lipopolissacarídeos/toxicidade , Western Blotting , Óxido Nítrico Sintase , Reação em Cadeia da Polimerase em Tempo Real
16.
Pest Manag Sci ; 80(10): 5452-5464, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38942611

RESUMO

BACKGROUND: Plant volatile organic compounds (VOCs) play a crucial role in mediating interactions between plants, herbivores and natural enemies. Among these VOCs, methyl salicylate and (E,E)-α-farnesene are emitted as herbivore-induced plant volatiles (HIPVs) by soybean plants in response to feeding by the brown stink bug Eushistus heros. These HIPVs function as synomones, influencing the foraging behaviour of the egg parasitoid, Telenomus podisi, the main natural enemy of E. heros, one of the major soybean pests in Brazil. RESULTS: Laboratory experiments showed that two soybean cultivars, BRS 7580 and BRS 7880, produced similar qualitative blends of HIPVs, with methyl salicylate, (E,E)-α-farnesene and (Z)-3-hexenyl acetate being produced by both cultivars. Soybean cultivar BRS 7580 produced a significant lower amount of HIPVs compared to BRS 7880 but this difference did not affect the attractiveness of the egg parasitoid Telenomus podisi. Field experiments using these two cultivars and synthetic applications of methyl salicylate and (E,E)-α-farnesene showed a substantial increase in egg parasitism in all treated areas. Parasitism rates ranged from 50% to 80% in areas where these HIPVs were deployed, compared to only 10% in untreated control areas. CONCLUSIONS: The egg parasitoid Telenomus podisi demonstrated an adept ability in recognising between HIPVs in soybean blends, even in the presence of significant quantitative differences. The results from the field experiment showed the potential of HIPVs in attracting natural enemies to specific target areas within fields. (E,E)-α-Farnesene showed an improved action during the later stages of soybean growth, notably at R6. In addition, this volatile attracted other families of natural enemies. © 2024 Society of Chemical Industry.


Assuntos
Glycine max , Heterópteros , Salicilatos , Sesquiterpenos , Vespas , Glycine max/parasitologia , Animais , Heterópteros/parasitologia , Heterópteros/fisiologia , Vespas/fisiologia , Vespas/efeitos dos fármacos , Óvulo/parasitologia , Óvulo/efeitos dos fármacos , Controle Biológico de Vetores , Compostos Orgânicos Voláteis , Herbivoria , Feminino
17.
Molecules ; 29(12)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38930909

RESUMO

In this work, a group of ten sesquiterpene drimanes, including polygodial (1), isopolygodial (2), and drimenol (3) obtained from the bark of Drimys winteri F. and seven synthetic derivatives, were tested in vitro against a unique panel of bacteria, fungi, and oomycetes with standardized procedures against bacterial strains K. pneumoniae, S. tiphy, E. avium, and E. coli. The minimum inhibitory concentrations and bactericidal activities were evaluated using standardized protocols. Polygodial (1) was the most active compound, with MBC 8 µg/mL and MIC 16 µg/mL in E. avium; MBC 16 µg/mL and MIC 32 µg/mL in K. pneumoniae; MBC 64 µg/mL and MIC 64 µg/mL in S. typhi; and MBC 8 µg/mL and MIC 16 µg/mL and MBC 32 µg/mL and MIC 64 µg/mL in E. coli, respectively. The observed high potency could be attributed to the presence of an aldehyde group at the C8-C9 position. The antifungal activity of 1 from different microbial isolates has been evaluated. The results show that polygodial affects the growth of normal isolates and against filamentous fungi and oomycetes with MFC values ranging from 8 to 64 µg/mL. Sesquiterpene drimanes isolated from this plant have shown interesting antimicrobial properties.


Assuntos
Anti-Infecciosos , Drimys , Testes de Sensibilidade Microbiana , Sesquiterpenos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Drimys/química , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos Policíclicos/química , Antibacterianos/farmacologia , Antibacterianos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Escherichia coli/efeitos dos fármacos , Fungos/efeitos dos fármacos , Bactérias/efeitos dos fármacos
18.
J Mol Model ; 30(7): 200, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850372

RESUMO

CONTEXT: Given the diverse pathophysiological mechanisms underlying Alzheimer's disease, it is improbable that a single targeted drug will prove successful as a therapeutic strategy. Therefore, exploring various hypotheses in drug design is imperative. The sequestration of Fe(II) and Zn(II) cations stands out as a crucial mechanism based on the mitigation of reactive oxygen species. Moreover, inhibiting acetylcholinesterase represents a pivotal strategy to enhance acetylcholine levels in the synaptic cleft. This research aims to investigate the analogs of Huperzine A, documented in scientific literature, considering of these two hypotheses. Consequently, the speciation chemistry of these structures with Fe(II) and Zn(II) was scrutinized using quantum chemistry calculations, molecular docking simulations, and theoretical predictions of pharmacokinetics properties. From the pharmacokinetic properties, only two analogs, HupA-A1 and HupA-A2, exhibited a theoretical permeability across the blood-brain barrier; on the other hand, from a thermodynamic standpoint, the enantiomers of HupA-A2 showed negligible chelation values. The enantiomers with the most favorable interaction parameters were S'R'HupA-A1 (ΔGBIND = -40.0 kcal mol-1, fitness score = 35.5) and R'R'HupA-A1 (ΔGBIND = -35.5 kcal mol-1, fitness score = 22.61), being compared with HupA (ΔGBIND = -41.75 kcal mol-1, fitness score = 39.95). From this study, some prime candidates for promising drug were S'R'HupA-A1 and R'R'HupA-A1, primarily owing to their favorable thermodynamic chelating capability and potential anticholinesterase mechanism. METHODS: Quantum chemistry calculations were carried out at B3LYP/6-31G(d) level, considering the IEF-PCM(UFF) implicit solvent model for water. The coordination compounds were assessed using the Gibbs free energy variation and hard and soft acid theory. Molecular docking calculations were conducted using the GOLD program, based on the crystal structure of the acetylcholinesterase protein (PDB code = 4EY5), where the ChemScore function was employed with the active site defined as the region within a 15-Å radius around the centroid coordinates (X = -9.557583, Y = -43.910473, Z = 31.466687). Pharmacokinetic properties were predicted using SwissADME, focusing on Lipinski's rule of five.


Assuntos
Acetilcolinesterase , Alcaloides , Doença de Alzheimer , Inibidores da Colinesterase , Simulação de Acoplamento Molecular , Sesquiterpenos , Doença de Alzheimer/tratamento farmacológico , Alcaloides/química , Sesquiterpenos/química , Humanos , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Acetilcolinesterase/metabolismo , Acetilcolinesterase/química , Barreira Hematoencefálica/metabolismo , Termodinâmica , Zinco/química , Modelos Moleculares , Ferro/química , Ferro/metabolismo
19.
Sci Rep ; 14(1): 14229, 2024 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902325

RESUMO

Natural products are an unsurpassed source of leading structures in drug discovery. The biosynthetic machinery of the producing organism offers an important source for modifying complex natural products, leading to analogs that are unattainable by chemical semisynthesis or total synthesis. In this report, through the combination of natural products chemistry and diversity-oriented synthesis, a diversity-enhanced extracts approach is proposed using chemical reactions that remodel molecular scaffolds directly on extracts of natural resources. This method was applied to subextract enriched in sesquiterpene lactones from Ambrosia tenuifolia (Fam. Asteraceae) using acid media conditions (p-toluenesulfonic acid) to change molecular skeletons. The chemically modified extract was then fractionated by a bioguided approach to obtain the pure compounds responsible for the anti-glioblastoma (GBM) activity in T98G cell cultures. Indeed, with the best candidate, chronobiological experiments were performed to evaluate temporal susceptibility to the treatment on GBM cell cultures to define the best time to apply the therapy. Finally, bioinformatics tools were used to supply qualitative and quantitative information on the physicochemical properties, chemical space, and structural similarity of the compound library obtained. As a result, natural products derivatives containing new molecular skeletons were obtained, with possible applications as chemotherapeutic agents against human GBM T98G cell cultures.


Assuntos
Glioblastoma , Extratos Vegetais , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Linhagem Celular Tumoral , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Asteraceae/química , Sesquiterpenos/química , Sesquiterpenos/farmacologia , Lactonas/química , Lactonas/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química
20.
Molecules ; 29(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38792102

RESUMO

This study investigates the chemical composition of the essential oil obtained from the leaves of Bocageopsis multiflora (Mart.) R.E.Fr (Annonaceae), examining its effectiveness in combating both the larvae and adult forms of Aedes aegypti mosquitoes. Additionally, for a deeper understanding of the insecticidal activity, toxicity properties and molecular docking calculations were conducted using the main compounds of this essential oil. GC/MS analysis revealed the presence of 26 constituents, representing 95.2% of the essential oil, with the major components identified as the sesquiterpenes α-selinene, ß-selinene, and ß-elemene. Larvicidal assays demonstrated potent activity of this essential oil with significant LC50 values of 40.8 and 39.4 µg/mL at 24 and 48 h, respectively. Adulticidal assessments highlighted strong efficacy with LC50 of 12.5 µg/mL. Molecular docking analysis identified optimal interaction activities of α-selinene and ß-selinene with key Aedes proteins. The in silico studies comparing synthetic insecticides with the major sesquiterpenes of the essential oil revealed that ß-selinene exhibited a significantly higher binding affinity compared to the other two sesquiterpenes. Also, ADMET studies of the three main sesquiterpenes indicated acceptable drug-like properties. In these findings, safety evaluations showed low toxicity and skin sensitization for the main sesquiterpenes, contrasting with commercial synthetic insecticides. Therefore, in silico analyses suggest promising interactions with Aedes proteins, indicating its potential as an effective alternative to conventional insecticides These results show the larvicidal and adulticidal potential of the essential oil from Bocageopsis multiflora against Aedes aegypti, supported by its predominant constituents, α-selinene, ß-selinene and ß-elemene.


Assuntos
Aedes , Inseticidas , Larva , Simulação de Acoplamento Molecular , Óleos Voláteis , Animais , Aedes/efeitos dos fármacos , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Inseticidas/química , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Folhas de Planta/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Cromatografia Gasosa-Espectrometria de Massas
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