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1.
Chem Biodivers ; 17(1): e1900496, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31909551

RESUMO

The genus Lavandula is known for its different uses in traditional medicine. This study is interested in the chemical composition of Lavandulapedunculata subsp.atlantica (Braun-Blanq.) Romo as well as evaluating its antibacterial potential against multi-resistant strains. The analysis of Lavandulaatlantica essential oil (LAEO) allows the identification of 47 components representing 93.6 % of all identified. The main constituent of LAEO was camphor (50.4 %), followed by fenchone (14.1 %) and camphene (5.6 %). The antibacterial assays revealed that LAEO was active against all the studied bacteria. A preliminary study of the relationship between certain terpenoids and antibacterial activity was also carried out in order to note the compound(s) that are responsible for LAEO's antibacterial activity. This study showed that the activity of the essential oil may be due to the presence of certain minor compounds such as carvone, considering the presence of the synergistic effect between the essential oil.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Lavandula/química , Óleos Voláteis/farmacologia , Terpenos/farmacologia , Antibacterianos/análise , Relação Dose-Resposta a Droga , Testes de Sensibilidade Microbiana , Óleos Voláteis/análise , Relação Estrutura-Atividade , Terpenos/análise
2.
Appl Microbiol Biotechnol ; 104(5): 2163-2178, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31980918

RESUMO

Tea tree oil (TTO) and its two characteristic components (terpinen-4-ol and 1,8-cineole) have been shown to inhibit Botrytis cinerea growth. In this study, we conducted a transcriptome analysis to determine the effects of TTO and its characteristic components, alone and in combination, against B. cinerea. Most differentially expressed genes (DEGs) from B. cinerea cells treated with terpinen-4-ol participated in the biosynthesis of secondary metabolites, and the metabolism of amino acids, carbohydrates, and lipids. All treatments containing terpinen-4-ol potentially induced mitochondrial dysfunction and oxidative stress. These were further confirmed by the decreased activities of several enzymes (e.g., succinate dehydrogenase (SDH), malate dehydrogenase (MDH), α-ketoglutarate dehydrogenase (α-KGDH), isocitrate dehydrogenase (ICDH)), the increased activities of certain enzymes (e.g., catalase (CAT), peroxidase (POD), superoxide dismutase (SOD)), and increased content of hydrogen peroxide (H2O2). 1,8-Cineole mainly affected DEGs involved in genetic information processing, resulting in cell death. This study provides insight into the molecular mechanism of B. cinerea inhibition by TTO, and explains the synergistic effect of terpinen-4-ol and 1,8-cineole on B. cinerea.


Assuntos
Antifúngicos/farmacologia , Botrytis/efeitos dos fármacos , Botrytis/genética , Óleo de Melaleuca/farmacologia , Antifúngicos/química , Botrytis/crescimento & desenvolvimento , Sinergismo Farmacológico , Eucaliptol/farmacologia , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Perfilação da Expressão Gênica , Peróxido de Hidrogênio/metabolismo , Óleo de Melaleuca/química , Terpenos/farmacologia , Transcriptoma/efeitos dos fármacos
3.
J Chem Ecol ; 46(1): 30-39, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31808075

RESUMO

Cerambycid beetles of the subfamily Lamiinae use male-produced aggregation-sex pheromones that are attractive to both sexes. Terpenoid pheromones have been identified from species in the tribes Acanthoderini and Acanthocinini native to North and South America, comprised of (E)-6,10-dimethyl-5,9-undecadien-2-one (geranylacetone), the structurally related 6-methylhept-5-en-2-one (sulcatone), and/or specific enantiomers or nonracemic ratios of enantiomers of the related compounds (E)-6,10-dimethyl-5,9-undecadien-2-ol (fuscumol), its acetate ester, (E)-6,10-dimethyl-5,9-undecadien-2-yl acetate (fuscumol acetate), and 6-methylhept-5-en-2-ol (sulcatol). Here, we present new information about the chemical ecology of six acanthoderine and acanthocinine species native to the eastern USA. The pheromone of Astyleiopus variegatus (Haldeman) previously was identified as a blend of (S)-fuscumol and (S)-fuscumol acetate, and we report here that geranylacetone is a synergistic component. Males of Aegomorphus modestus (Gyllenhal), Lepturges angulatus (LeConte), and Lepturges confluens (Haldeman) were found to produce similar blends composed of the enantiomers of fuscumol acetate and geranylacetone, whereas males of Astylidius parvus (LeConte) and Sternidius alpha (Say) produced both enantiomers of fuscumol together with (R)-fuscumol acetate and geranylacetone. Field experiments with synthesized chemicals revealed that species with similar pheromone composition nevertheless differed in their responses to individual components, and to various blends of components, and in how attraction was influenced by chemicals that were pheromone components of other species. Sulcatone and/or sulcatol antagonized attraction of some species to pheromones of the geranylacetone class, suggesting that there is an adaptive advantage in an ability to detect these heterospecific compounds, such as in avoiding cross attraction to other cerambycid species, as yet unknown, that use pheromones composed of both chemical classes.


Assuntos
Besouros/química , Feromônios/química , Animais , Besouros/metabolismo , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Masculino , Feromônios/isolamento & purificação , Feromônios/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Especificidade da Espécie , Estereoisomerismo , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/isolamento & purificação , Compostos Orgânicos Voláteis/farmacologia
4.
J Enzyme Inhib Med Chem ; 35(1): 152-164, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31742469

RESUMO

Overexpression of protein tyrosine phosphatase 1B (PTP1B) induces insulin resistance in various basic and clinical research. In our previous work, a synthetic oleanolic acid (OA) derivative C10a with PTP1B inhibitory activity has been reported. However, C10a has some pharmacological defects and cytotoxicity. Herein, a structure-based drug design approach was used based on the structure of C10a to elaborate the smaller tricyclic core. A series of tricyclic derivatives were synthesised and the compounds 15, 28 and 34 exhibited the most PTP1B enzymatic inhibitory potency. In the insulin-resistant human hepatoma HepG2 cells, compound 25 with the moderate PTP1B inhibition and preferable pharmaceutical properties can significantly increase insulin-stimulated glucose uptake and showed the insulin resistance ameliorating effect. Moreover, 25 showed the improved in vivo antihyperglycaemic potential in the nicotinamide-streptozotocin-induced T2D. Our study demonstrated that these tricyclic derivatives with improved molecular architectures and antihyperglycaemic activity could be developed in the treatment of T2D.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Desenho de Drogas , Inibidores Enzimáticos/farmacologia , Hipoglicemiantes/farmacologia , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Terpenos/farmacologia , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Células Hep G2 , Humanos , Hipoglicemiantes/síntese química , Hipoglicemiantes/química , Resistência à Insulina , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Proteína Tirosina Fosfatase não Receptora Tipo 1/metabolismo , Relação Estrutura-Atividade , Terpenos/síntese química , Terpenos/química
5.
Eur J Med Chem ; 185: 111806, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31677446

RESUMO

In this work, 35 new derivatives of betulonic, dihydrobetulonic and ursonic acid were prepared including 30 aminothiazoles and all of them were tested for their in vitro cytotoxic activity in eight cancer cell lines and two non-cancer fibroblasts. Compounds with the IC50 below 5 µM in CCRF-CEM cells and low toxicity in non-cancer fibroblasts (4m, 5c, 5m, 6c, 6m, 7b, and 7c) were further subjected to tests of pharmacological parameters yielding the final set for advanced biological evaluation (4m, 5m, 6m, and 7b). It was proved by several methods, that all of them trigger apoptosis via the intrinsic pathway and derivatives 5m and 7b are the most effective (IC50 2.4 µM and 3.6 µM). They are the best candidates to become potentially new anticancer drugs and will be subjected to in vivo tests in mice. In addition, compounds 6b and 6c deserve more attention because their activity is not limited only to chemosensitive CCRF-CEM cell line. Specifically, compound 6b is highly active against K562 leukemic cell line (0.7 µM) and its IC50 activity in colon cancer HCT116 cell line is 1.0 µM. Compound 6c is active in both normal K562 and resistant K562-TAX cell lines (IC50 3.4 µM and 5.4 µM) and both colon cancer cell lines (HCT116 and HCT116p53-/-, IC50 3.5 µM and 3.4 µM).


Assuntos
Antineoplásicos/farmacologia , Ácido Oleanólico/análogos & derivados , Terpenos/farmacologia , Tiazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Fibroblastos/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microssomos/química , Microssomos/metabolismo , Estrutura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Relação Estrutura-Atividade , Terpenos/síntese química , Terpenos/química , Tiazóis/síntese química , Tiazóis/química
6.
BMC Complement Altern Med ; 19(1): 365, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31830975

RESUMO

BACKGROUND: The edible fruit Annona cherimola has previously shown many nutritional and medicinal properties. The current study evaluates the anti-cancer and anti-proliferative properties of Annona cherimola ethanolic leaf extract (AELE) on Acute Myeloid Leukemia (AML) cell lines cultured in vitro (Monomac-1 and KG-1). METHODS: The anti-proliferative effect of A. cherimola ethanolic leaf extract was evaluated via cell viability assay. Its pro-apoptotic effect was assessed through Cell Death ELISA and dual Annexin V/PI staining. To further investigate the molecular mechanism by which the extract promoted apoptosis and inhibited the proliferation of the AML cells used, apoptotic protein expression was determined through western blots. Extract composition was elucidated by Gas Chromatography-Mass Spectrometry (GC-MS). RESULTS: Our results showed that the treatment with A. cherimola ethanolic leaf extract exhibited an inhibitory effect on the proliferation of both cancer cell lines used in a dose- and time-dependent manner, with no toxic effects on normal mononuclear cells (MNCs) isolated from human bone marrow. This effect was mediated by DNA fragmentation and apoptosis, as revealed by Cell Death ELISA and dual Annexin V/PI staining. Western blot analysis revealed a Bax/Bcl2 dependent mechanism of apoptosis, as well as PARP cleavage, confirming the apoptotic results observed previously. These effects may be attributed to the presence of terpenes which constitute a large component of the leafy extract, as revealed via GC-MS. CONCLUSION: All the data presented in our study show that the terpene-rich A. cherimola ethanolic leaf extract exhibits an anti-proliferative and pro-apoptotic effect on the AML cell lines used.


Assuntos
Annona , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Terpenos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Leucemia Mieloide Aguda , Folhas de Planta/química
7.
Fitoterapia ; 139: 104358, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31629047

RESUMO

Nine new isoprenoids, named as dictamtrinor-guaianols A (1), B (2), C (3), D (4), and E (5), dictamnorsesquiterpenol A (6), dictamnorsesquiterpenosides B (7) and C (8), as well as dictamtriterpenol A (9), along with eight known compounds (10-17) were obtained from 70% EtOH extract of Cortex Dictamni. Their structures were ascertained based on the extensive spectroscopic methods and ECD data analysis. Moreover, LC-MS analysis result suggested compounds 2 and 3 were natural products. Furthermore, lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage model were used to evaluate nitric oxide production inhibitory activities of them, and compounds 2, 3, 5, 6, 8-11, as well as 15-17 displayed significant activities at 40 µM.


Assuntos
Dictamnus/química , Óxido Nítrico/metabolismo , Terpenos/farmacologia , Animais , China , Camundongos , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Raízes de Plantas/química , Células RAW 264.7 , Sesquiterpenos/isolamento & purificação , Sesquiterpenos/farmacologia , Terpenos/isolamento & purificação
8.
BMC Infect Dis ; 19(1): 800, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510931

RESUMO

BACKGROUND: Larviciding is an effective supplementary tool for malaria vector control, but the identification and accessibility of aquatic habitats impedes application. Dissemination of the insect growth regulator, pyriproxyfen (PPF), by gravid Anopheles might constitute a novel application strategy. This study aimed to explore the feasibility of using an attractive bait-station to contaminate gravid Anopheles gambiae sensu stricto with PPF and subsequently transfer PPF to larval habitats. METHODS: A bait-station was developed comprising of an artificial pond containing water treated with 20 ppm cedrol, an oviposition attractant, and a netting-cover treated with PPF. Three identical semi-field cages were used to assess the potential of gravid Anopheles to transfer PPF from the bait-station to ponds. Gravid females were released in two semi-field cages, one with PPF on its bait-station (test) and one without PPF (control). No mosquitoes were released in the third cage with a PPF-treated station (control). Transfer of PPF to open ponds was assessed by monitoring emergence of late instar insectary-reared larvae introduced into the ponds. The amount of PPF carried by a mosquito and transferred to water was quantified using liquid chromatography-mass spectrometry. RESULTS: In the controls, 86% (95% CI 81-89%) of larvae introduced into open ponds developed into adults, indicating that wind did not distribute PPF in absence of mosquitoes. Emergence inhibition was observed in the test cage but was dependent on the distance between pond and bait-station. Only 25% (95% CI 22-29%) of larvae emerged as adults from ponds 4 m from the bait-station, but 92% (95% CI 89-94%) emerged from ponds 10 m away. Each mosquito was contaminated on average with 112 µg (95% CI 93-123 µg) PPF resulting in the transfer of 230 ng/L (95% CI 180-290 ng/L) PPF to 100 ml volumes of water. CONCLUSIONS: The bait-stations successfully attracted gravid females which were subsequently dusted with effective levels of PPF. However, in this study design, attraction and dissemination was limited to short distances. To make this approach feasible for malaria vector control, stronger attractants that lure gravid females from longer distances, in landscapes with many water bodies, and better PPF delivery systems are needed.


Assuntos
Anopheles/efeitos dos fármacos , Inseticidas/toxicidade , Controle de Mosquitos/métodos , Piridinas/toxicidade , Animais , Anopheles/crescimento & desenvolvimento , Anopheles/fisiologia , Feminino , Larva/efeitos dos fármacos , Oviposição , Tanques , Terpenos/farmacologia
9.
Eur J Med Chem ; 182: 111652, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494470

RESUMO

Farnesoid X receptor (FXR) is a key regulator in charge of bile acid synthesis, transport, and metabolism. Activation of FXR represses bile acid synthesis and increases its excretion and transport, consequently protecting the liver functions. Thus, FXR is considered as a critical therapeutic target of cholestasis and nonalcoholic steatohepatitis. Herein, we isolated and identified fourteen new protostane-type triterpenoids (1-14) and four known analogues (15-18) from Alisma orientale, and finally constructed a small library of protostane-type triterpenoids (1-70) to investigate their structure-activity relationship with FXR, further leading to obtain compound 15 with potent agonistic activity against FXR (EC50 = 90 nM). Extensive in vitro investigation confirmed high efficacy of compound 15 against FXR in living cell, and revealed its underlying mechanism for FXR activation (amino acid residues Arg331 and Ser332) by molecular docking and site-directed mutagenesis technology.


Assuntos
Produtos Biológicos/farmacologia , Receptores Citoplasmáticos e Nucleares/agonistas , Terpenos/farmacologia , Alisma/química , Produtos Biológicos/química , Produtos Biológicos/isolamento & purificação , Células Cultivadas , Relação Dose-Resposta a Droga , Células Hep G2 , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Mutagênese Sítio-Dirigida , Receptores Citoplasmáticos e Nucleares/genética , Relação Estrutura-Atividade , Terpenos/química , Terpenos/isolamento & purificação
10.
J Chem Ecol ; 45(10): 888-900, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493165

RESUMO

Interactions between water stress and induced defenses and their role in tree mortality due to bark beetles are poorly understood. We performed a factorial experiment on 48 mature ponderosa pines (Pinus ponderosa) in northern Arizona over three years that manipulated a) tree water stress by cutting roots and removing snow; b) bark beetle attacks by using pheromone lures; and c) phloem exposure to biota vectored by bark beetles by inoculating with dead beetles. Tree responses included resin flow from stem wounds, phloem composition of mono- and sesqui-terpenes, xylem water potential, leaf gas exchange, and survival. Phloem contained 21 mono- and sesqui-terpenes, which were dominated by (+)-α-pinene, (-)-limonene, and δ-3-carene. Bark beetle attacks (mostly Dendroctonus brevicomis) and biota carried by beetles induced a general increase in concentration of phloem mono- and sesqui-terpenes, whereas water stress did not. Bark beetle attacks induced an increase in resin flow for unstressed trees but not water-stressed trees. Mortality was highest for beetle-attacked water-stressed trees. Death of beetle-attacked trees was preceded by low resin flow, symptoms of water stress (low xylem water potential, leaf gas exchange), and an ephemeral increase in concentrations of mono- and sesqui-terpenes compared to surviving trees. These results show a) that ponderosa pine can undergo induction of both resin flow and phloem terpenes in response to bark beetle attack, and that the former is more constrained by water stress; b) experimental evidence that water stress predisposes ponderosa pines to mortality from bark beetles.


Assuntos
Besouros/fisiologia , Secas , Interações Hospedeiro-Parasita/efeitos dos fármacos , Pinus ponderosa/química , Terpenos/farmacologia , Animais , Cromatografia Gasosa , Pinus ponderosa/metabolismo , Casca de Planta/química , Casca de Planta/metabolismo , Resinas Vegetais/química , Resinas Vegetais/metabolismo , Estações do Ano , Terpenos/análise , Terpenos/química
11.
Phytomedicine ; 60: 152977, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31474477

RESUMO

BACKGROUND: Intrigued by testimonies of Saxon borreliosis self-help groups concerning considerabl improvements of their symptoms by ingestion of Cistus creticus L. (Cistaceae) leaf preparations, we recently reported on the growth inhibiting activity of extracts with different polarities and its volatile oil against Borrelia burgdorferi sensu stricto (Bbss) in vitro, determined by a bioassay guided procedure. The most active volatile oil (only about 0.10% in leaves) was found to be dominated by labdane-type manoyloxides as well as carvacrol, determined via GC-MS. HYPOTHESIS: These terpenes are major active constituents of the old pharmaceutical oleoresin labdanum, which is secreted from the leaf surface of C. creticus and traditionally harvested, e.g., on Crete by brushing the shrubs. METHODS: In order to elucidate the definite anti-Borrelia active principles of C. creticus, preparative scale separation of the diethyl­ether soluble fraction of Cretan labdanum was achieved by combined silica gel 60-and RP-18 CC and analysed by novel TLC-Extractor/ES-MS as well as by 1d/2d-1H/13C-NMR data. For the antispirochaetal activity tests against Bbss in vitro, all samples were solubilised in water with addition of polysorbate 80, the effect of which on bacterial growth was examined and found to be negligible. RESULTS: This led to isolation and identification of the monoterpene carvacrol as well as of the four major manoyloxides manoyloxide (A), 3-acetoxy-manoyloxide (B), 3­hydroxy-manoyloxide (C), and epi­manoyloxide (D). Additionally, 2-keto-manoyloxide (E) and sclareol (F) were identified via GC/EI-MS. In subsequent microbiological tests of the isolated compounds, epi­manoyloxide (D) exhibited by far the strongest individual antispirochaetal effect, equal to the positive control amoxicilline. Furthermore, manoyloxide (A), carvacrol, and the diethyl­ether soluble fraction of labdanum as a whole contribute to the strong antispirochaetal activity, while the other labdanes were less active. Isolated manoyloxides were further used as external standards for a GC-MS screening of labdanum samples from different origins, revealing exceptionally high contents of all analysed manoyloxides in the samples of Cretan labdanum from C. creticus, while their contents in other commercial available labdanum samples were lower by several orders of magnitude. Especially in Spanish labdanum samples, declared as Cistus ladanifer L., mainly simple alkanes and at most traces of epi­manoyloxide (D) and of manoyloxide (A) could be detected. CONCLUSION: The application of C. creticus preparations by Lyme disease self-help groups may be considered as a reasonable therapy approach. For the first time, isolated epi­manoyloxide and carvacrol could be evaluated as most promising candidates for drug development and labdanum based phytomedicine development, respectively. They should serve as vital active markers for quality assessments of C. creticus preparations.


Assuntos
Antibacterianos/farmacologia , Borrelia/efeitos dos fármacos , Cistus/química , Diterpenos/farmacologia , Antibacterianos/isolamento & purificação , Diterpenos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Grécia , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta/química , Terpenos/isolamento & purificação , Terpenos/farmacologia
12.
Chem Biodivers ; 16(9): e1900366, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31386266

RESUMO

The natural polyisoprenylated benzophenone derivatives garcinol and isogarcinol are secondary plant metabolites isolated from various Garcinia species including Garcinia indica. This review takes stock of the recent chemical and biological research into these interesting natural compounds over the last five years. New biological sources and chemical syntheses are discussed followed by new insights into the activity of garcinol and isogarcinol against cancer, pathogenic bacteria, parasite infections and various inflammatory diseases.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antiprotozoários/farmacologia , Neoplasias/tratamento farmacológico , Terpenos/farmacologia , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antiprotozoários/química , Antiprotozoários/isolamento & purificação , Garcinia/química , Humanos , Terpenos/química , Terpenos/isolamento & purificação
13.
Fitoterapia ; 138: 104293, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398447

RESUMO

Herbal medicines (HMs) have attracted widespread attention because of their significant contributions to the prevention and treatment of many human diseases. Recently, gut microbiota has become an important frontier to understand the therapeutic mechanisms of medicines. Gut microbiota-mediated transformation is a microbial metabolic form after oral administrations of HMs compounds. A great number of studies showed that gut microbiota could transform some HMs compounds by the variation of chemical structures into several active metabolites, which exerted better bioavailabilities and therapeutic activities than their parent compounds. Among these HMs compounds, alkaloids, flavonoids, polyphenols and terpenoids were the representative ones. However, there is no systemic review focusing on the potential improved therapeutic activities of these natural compounds caused by gut microbial transformation. Here, this review summarizes the therapeutic activities that are more potent in microbial transformed metabolites than in their parent compounds (alkaloids, flavonoids, polyphenols and terpenoids) from HMs. We hope this review will be conducive to deepening the understanding of the relationship between gut microbial transformation and therapeutic activities of HMs compounds.


Assuntos
Alcaloides/metabolismo , Flavonoides/metabolismo , Microbioma Gastrointestinal , Preparações de Plantas/metabolismo , Polifenóis/metabolismo , Terpenos/metabolismo , Alcaloides/farmacologia , Disponibilidade Biológica , Flavonoides/farmacologia , Humanos , Compostos Fitoquímicos/metabolismo , Compostos Fitoquímicos/farmacologia , Preparações de Plantas/farmacologia , Plantas Medicinais/química , Polifenóis/farmacologia , Terpenos/farmacologia
14.
Molecules ; 24(16)2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31405117

RESUMO

Two new terpene glycosides (1-2) along with two known analogs (3-4) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1-4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.


Assuntos
Anti-Inflamatórios , Glicosídeos , Sanguisorba/química , Terpenos , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Glicosídeos/química , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Interleucina-6/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Células RAW 264.7 , Terpenos/química , Terpenos/isolamento & purificação , Terpenos/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Peixe-Zebra
15.
Molecules ; 24(17)2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31438532

RESUMO

Mixtures of different Cannabis sativa phytocannabinoids are more active biologically than single phytocannabinoids. However, cannabis terpenoids as potential instigators of phytocannabinoid activity have not yet been explored in detail. Terpenoid groups were statistically co-related to certain cannabis strains rich in Δ9-tetrahydrocannabinolic acid (THCA) or cannabidiolic acid (CBDA), and their ability to enhance the activity of decarboxylase phytocannabinoids (i.e., THC or CBD) was determined. Analytical HPLC and GC/MS were used to identify and quantify the secondary metabolites in 17 strains of C. sativa, and correlations between cannabinoids and terpenoids in each strain were determined. Column separation was used to separate and collect the compounds, and cell viability assay was used to assess biological activity. We found that in "high THC" or "high CBD" strains, phytocannabinoids are produced alongside certain sets of terpenoids. Only co-related terpenoids enhanced the cytotoxic activity of phytocannabinoids on MDA-MB-231 and HCT-116 cell lines. This was found to be most effective in natural ratios found in extracts of cannabis inflorescence. The correlation in a particular strain between THCA or CBDA and a certain set of terpenoids, and the partial specificity in interaction may have influenced the cultivation of cannabis and may have implications for therapeutic treatments.


Assuntos
Canabinoides/farmacologia , Cannabis/química , Terpenos/farmacologia , Canabinoides/química , Carboxiliases/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Cromatografia Gasosa-Espectrometria de Massas , Células HCT116 , Humanos , Terpenos/química
16.
Biomed Res Int ; 2019: 2931831, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31392210

RESUMO

Background: The apolipoprotein E knockout (ApoE -/-) mouse model is well established for the study of terpenoids in the prevention of atherosclerosis. Studies investigating the clinical benefit of terpenoids in humans are scarce. This systematic review and meta-analysis evaluated the effects of terpenoid administration on atherosclerotic lesion area in ApoE -/- mice. Methods: A comprehensive literature search using PubMed, Embase, and the Cochrane Library databases was performed to identify studies that assessed the effects of terpenoids on atherosclerosis in ApoE -/- mice. The primary outcome was atherosclerotic lesion area, and study quality was estimated using SYRCLE's risk of bias tool. Results: The meta-analysis included 25 studies. Overall, terpenoids significantly reduced atherosclerotic lesion area when compared to vehicle control (P<0.00001; SMD: -0.55; 95% CI: -0.72, -0.39). In terpenoid type and dose subgroup analyses, sesquiterpenoid (P=0.002; SMD -0.93; 95% CI: -1.52, -0.34), diterpenoid (P=0.01; SMD: -0.30; 95% CI: -0.54, -0.06), triterpenoid (P<0.00001; SMD: -0.66; 95% CI: -0.94, -0.39), tetraterpenoid (P<0.0001; SMD: -1.81; 95% CI: -2.70, -0.91), low dose (P=0.0001; SMD: -0.51; 95% CI: -0.76, -0.25), medium dose (P<0.0001; SMD: -0.48; 95% CI: -0.72, -0.24), and high dose (P=0.002; SMD: -1.07; 95% CI: -1.74, -0.40) significantly decreased atherosclerotic lesion area when compared to vehicle control. PROSPERO register number is CRD42019121176. Conclusion: Sesquiterpenoid, diterpenoid, triterpenoid, and tetraterpenoid have potential as antiatherosclerotic agents with a wide range of doses. This systematic review provides a reference for research programs aimed at the development of terpenoid-based clinical drugs.


Assuntos
Doenças da Aorta/prevenção & controle , Aterosclerose/prevenção & controle , Terpenos/farmacologia , Animais , Doenças da Aorta/genética , Doenças da Aorta/metabolismo , Doenças da Aorta/patologia , Aterosclerose/genética , Aterosclerose/metabolismo , Aterosclerose/patologia , Modelos Animais de Doenças , Camundongos , Camundongos Knockout para ApoE , PubMed
17.
Molecules ; 24(13)2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31324047

RESUMO

Quinoa (Chenopodium quinoa Willd.) was known as the "golden grain" by the native Andean people in South America, and has been a source of valuable food over thousands of years. It can produce a variety of secondary metabolites with broad spectra of bioactivities. At least 193 secondary metabolites from quinoa have been identified in the past 40 years. They mainly include phenolic acids, flavonoids, terpenoids, steroids, and nitrogen-containing compounds. These metabolites exhibit many physiological functions, such as insecticidal, molluscicidal and antimicrobial activities, as well as various kinds of biological activities such as antioxidant, cytotoxic, anti-diabetic and anti-inflammatory properties. This review focuses on our knowledge of the structures, biological activities and functions of quinoa secondary metabolites. Biosynthesis, development and utilization of the secondary metabolites especially from quinoa bran were prospected.


Assuntos
Chenopodium quinoa/química , Chenopodium quinoa/metabolismo , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Metabolismo Secundário , Flavonoides/química , Flavonoides/metabolismo , Flavonoides/farmacologia , Hidroxibenzoatos/química , Hidroxibenzoatos/metabolismo , Hidroxibenzoatos/farmacologia , Compostos Fitoquímicos/metabolismo , Relação Estrutura-Atividade , Terpenos/química , Terpenos/metabolismo , Terpenos/farmacologia
18.
Molecules ; 24(14)2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31330955

RESUMO

The evolution of antimicrobial resistance (AMR) in pathogens has prompted extensive research to find alternative therapeutics. Plants rich with natural secondary metabolites are one of the go-to reservoirs for discovery of potential resources to alleviate this problem. Terpenes and their derivatives comprising of hydrocarbons, are usually found in essential oils (EOs). They have been reported to have potent antimicrobial activity, exhibiting bacteriostatic and bactericidal effects against tested pathogens. This brief review discusses the activity of terpenes and derivatives against pathogenic bacteria, describing the potential of the activity against AMR followed by the possible mechanism exerted by each terpene class. Finally, ongoing research and possible improvisation to the usage of terpenes and terpenoids in therapeutic practice against AMR are discussed.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Resistência Microbiana a Medicamentos/efeitos dos fármacos , Terpenos/química , Terpenos/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade
19.
Molecules ; 24(14)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315175

RESUMO

There is a growing interest in a potential use of essential oils (EOs) as a replacement for traditional pesticides and herbicides. The aims of this study were to: (i) Identify the chemical composition of the two EOs derived from Origanum heracleoticum L. and O. majorana L., (ii) evaluate the in vitro antifungal activity of the EOs against some postharvest phytopathogens (Botrytis cinerea, Penicillium expansum, Aspergillus niger and Monilinia fructicola), (iii) evaluate the in vitro antibacterial activity against Bacillus megaterium, Clavibacter michiganensis, Xanthomonas campestris, Pseudomonas fluorescens and P. syringae pv. phaseolicola, (iv) evaluate the effect of both studied EOs on the spore germination percentage and their minimum inhibitory concentration (MIC) against M. fructicola, and (v) study the possible phytotoxicity of the two EOs and their major constituents, carvacrol for O. heracleoticum and terpinen-4-ol for O. majorana, against tha germination and initial radicle growth of radish, lettuce, garden cress and tomato. The two EOs demonstrated promising in vitro antimicrobial and antifungal activities against all tested microorganisms. EOs showed high inhibition of spore germination percentage at the minimal inhibitory concentration of 500 and 2000 µg/mL, respectively. Moreover, both germination and radical elongation of selected plant species were sensitive to the oils.


Assuntos
Anti-Infecciosos/química , Óleos Voláteis/química , Origanum/química , Esporos/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Lepidium sativum/crescimento & desenvolvimento , Lepidium sativum/microbiologia , Alface/crescimento & desenvolvimento , Alface/microbiologia , Lycopersicon esculentum/crescimento & desenvolvimento , Lycopersicon esculentum/microbiologia , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Raphanus/crescimento & desenvolvimento , Raphanus/microbiologia , Terpenos/farmacologia
20.
Molecules ; 24(13)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284397

RESUMO

Background: The antimicrobial activity of essential oils has been reported in hundreds of studies, however, the great majority of these studies attribute the activity to the most prevalent compounds without analyzing them independently. Therefore, the aim was to investigate the antibacterial activity of 33 free terpenes commonly found in essential oils and evaluate the cellular ultrastructure to verify possible damage to the cellular membrane. Methods: Screening was performed to select substances with possible antimicrobial activity, then the minimal inhibitory concentrations, bactericidal activity and 24-h time-kill curve studies were evaluated by standard protocols. In addition, the ultrastructure of control and death bacteria were evaluated by scanning electron microscopy. Results: Only 16 of the 33 compounds had antimicrobial activity at the initial screening. Eugenol exhibited rapid bactericidal action against Salmonella enterica serovar Typhimurium (2 h). Terpineol showed excellent bactericidal activity against S. aureus strains. Carveol, citronellol and geraniol presented a rapid bactericidal effect against E. coli. Conclusions: The higher antimicrobial activity was related to the presence of hydroxyl groups (phenolic and alcohol compounds), whereas hydrocarbons resulted in less activity. The first group, such as carvacrol, l-carveol, eugenol, trans-geraniol, and thymol, showed higher activity when compared to sulfanilamide. Images obtained by scanning electron microscopy indicate that the mechanism causing the cell death of the evaluated bacteria is based on the loss of cellular membrane integrity of function. The present study brings detailed knowledge about the antimicrobial activity of the individual compounds present in essential oils, that can provide a greater understanding for the future researches.


Assuntos
Antibacterianos/farmacologia , Óleos Voláteis/química , Terpenos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/ultraestrutura , Testes de Sensibilidade Microbiana , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/ultraestrutura , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/ultraestrutura
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