RESUMO
The genus Clusia L. is highly diverse in Central and South America, comprising about 300 species, including trees and shrubs, hemiepiphytes, epiphytes, and lianas. This genus deserves attention due to its wide range of biological activities. Clusia belongs to the Clusiaceae family, chemically characterized by the presence of xanthones, benzophenones, flavonoids, coumarins, terpenoids, and other substances with bioactive activity already described. This review aims to highlight the biological activity associated to extracts and isolated substances from species of the Clusia genus, including anti-HIV, antimicrobial, antioxidant, antinociceptive, antitumor, leishmanicidal, modulator of inflammatory processes, neutralization of toxic effects caused by snake bites, and others. This review gathered information on biological activities associated with different types of extracts and isolated substances of the genus Clusia, traditional use, chemical profile, and biological properties of plants of the genus, published in the last 23 years (1998 to 2021) and that can provide support for future research. The paper aims to provide an overview of existing knowledge about the biological properties of the genus Clusia plant species.
Assuntos
Extratos Vegetais , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Clusiaceae/química , Clusiaceae/classificação , Humanos , Animais , Antioxidantes/farmacologia , Anti-Infecciosos/farmacologiaRESUMO
The chemical constituents from the stems and leaves of Cratoxylum cochinchinense were isolated and purified using silica gel, ODS gel, and Sephadex LH-20 gel column chromatography, as well as preparative HPLC. The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, and the comparison of their physicochemical and spectroscopic data with the reported data in literature. As a result, 21 compounds were isolated from the 90% ethanol extract of the stems and leaves of C. cochinchinense, which were identified as cratocochine(1), 1-hydroxy-3,7-dimethoxyxanthone(2), 1-hydroxy-5,6,7-trimethoxyxanthone(3), ferrxanthone(4), 3,6-dihydroxy-1,5-dimethoxyxanthone(5), 3,6-dihydroxy-1,7-dimethoxyxanthone(6), 1,2,5-trihydroxy-6,8-dimethoxyxanthone(7), securixanthone G(8), gentisein(9), 3,7-dihydroxy-1-methoxyxanthone(10), pancixanthone B(11), garcimangosxanthone A(12), pruniflorone L(13), 9-hydroxy alabaxanthone(14), cochinchinone A(15), luteolin(16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol(17), N-benzyl-9-oxo-10E,12E-octadecadienamide(18), 15-hydroxy-7,13E-labdadiene(19), stigmasta-4,22-dien-3-one(20), and stigmast-5-en-3ß-ol(21). Among these isolates, compound 1 was a new xanthone, compounds 2-5, 7, 8, 12, and 16-21 were isolated from the Cratoxylum plant for the first time, and compounds 11 and 13 were obtained from C. cochinchinense for the first time. Furthermore, all isolated compounds 1-21 were appraised for their anti-rheumatoid arthritis activities by MTS method through measuring their anti-proliferative effect on synoviocytes in vitro. As a result, xanthones 1-15 displayed notable anti-rheumatoid arthritis activities, which showed inhibitory effects on the proliferation of MH7A synoviocytes with the IC_(50) values ranging from(8.98±0.12) to(228.68±0.32) µmol·L~(-1).
Assuntos
Artrite , Clusiaceae , Sinoviócitos , Xantonas , Clusiaceae/química , Xantonas/farmacologia , Xantonas/análise , Folhas de Planta/química , Proliferação de CélulasRESUMO
Guttiferones belong to the polyisoprenylated benzophenone, a class of compounds, a very restricted group of natural plant products, especially in the Clusiaceae family. They are commonly found in bark, stem, leaves, and fruits of plants of the genus Garcinia and Symphonia. Guttiferones have the following classifications according to their chemical structure: A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, and T. All of them have received growing attention due to its multiple biological activities. This review provides a first comprehensive approach to plant sources, phytochemical profile, specific pharmacological effects, and mechanisms of guttiferones already described. Studies indicate a broad spectrum of pharmacological activities, such as: anti-inflammatory, immunomodulatory, antioxidant, antitumor, antiparasitic, antiviral, and antimicrobial. Despite the low toxicity of these compounds in healthy cells, there is a lack of studies in the literature related to toxicity in general. Given their beneficial effects, guttiferones are expected to be great potential drug candidates for treating cancer and infectious and transmissible diseases. However, further studies are needed to elucidate their toxicity, specific molecular mechanisms and targets, and to perform more in-depth pharmacokinetic studies. This review highlights chemical properties, biological characteristics, and mechanisms of action so far, offering a broad view of the subject and perspectives for the future of guttiferones in therapeutics.
Assuntos
Clusiaceae , Clusiaceae/química , Extratos Vegetais/farmacologia , Compostos Fitoquímicos/farmacologiaRESUMO
The chemical constituents from the stems and leaves of Cratoxylum cochinchinense were isolated and purified using silica gel, ODS gel, and Sephadex LH-20 gel column chromatography, as well as preparative HPLC. The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, and the comparison of their physicochemical and spectroscopic data with the reported data in literature. As a result, 21 compounds were isolated from the 90% ethanol extract of the stems and leaves of C. cochinchinense, which were identified as cratocochine(1), 1-hydroxy-3,7-dimethoxyxanthone(2), 1-hydroxy-5,6,7-trimethoxyxanthone(3), ferrxanthone(4), 3,6-dihydroxy-1,5-dimethoxyxanthone(5), 3,6-dihydroxy-1,7-dimethoxyxanthone(6), 1,2,5-trihydroxy-6,8-dimethoxyxanthone(7), securixanthone G(8), gentisein(9), 3,7-dihydroxy-1-methoxyxanthone(10), pancixanthone B(11), garcimangosxanthone A(12), pruniflorone L(13), 9-hydroxy alabaxanthone(14), cochinchinone A(15), luteolin(16), 3,5'-dimethoxy-4',7-epoxy-8,3'-neolignane-5,9,9'-triol(17), N-benzyl-9-oxo-10E,12E-octadecadienamide(18), 15-hydroxy-7,13E-labdadiene(19), stigmasta-4,22-dien-3-one(20), and stigmast-5-en-3β-ol(21). Among these isolates, compound 1 was a new xanthone, compounds 2-5, 7, 8, 12, and 16-21 were isolated from the Cratoxylum plant for the first time, and compounds 11 and 13 were obtained from C. cochinchinense for the first time. Furthermore, all isolated compounds 1-21 were appraised for their anti-rheumatoid arthritis activities by MTS method through measuring their anti-proliferative effect on synoviocytes in vitro. As a result, xanthones 1-15 displayed notable anti-rheumatoid arthritis activities, which showed inhibitory effects on the proliferation of MH7A synoviocytes with the IC_(50) values ranging from(8.98±0.12) to(228.68±0.32) μmol·L~(-1).
Assuntos
Sinoviócitos , Clusiaceae/química , Xantonas/análise , Folhas de Planta/química , Proliferação de Células , ArtriteRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: The tribe Symphonieae (Clusiaceae) encompasses 48 species accommodated in seven genera (Lorostemon, Montrouziera, Moronobea, Pentadesma, Platonia, Symphonia and Thysanostemon). Parts of these plants, mainly the exudates and the seeds oil are useful for different purposes, especially for treating dermatological conditions. In addition to the role in the folk medicine, some species are of great economic and cultural importance for native people from different continents. AIM OF THE REVIEW: The goal of this review is to critically summarize the current knowledge on systematics, ethnobotanical, chemical and pharmacological aspects of species from the tribe Symphonieae, as well as to provide support for future taxonomic and phylogenetic studies on the Clusiaceae family. MATERIALS AND METHODS: The available information was gathered from many different databases (Web of Science, ScienceDirect, Scopus, Pubmed, ChemSpider, SciFinder, ACS Publications, Wiley Online Library, Useful Tropical Plants Database, Google Scholar). Additional data from books, theses and dissertations were also included in this review. RESULTS: Chemical studies of Symphonieae have demonstrated that the genera are a source of benzophenones, xanthones and biflavonoids. Components as sesquiterpenoids, triterpenoids, flavonoids, free fatty acids, among others, have also been reported. Extracts and compounds isolated from a variety of species have been exhibiting antimicrobial, cytotoxic and antiprotozoal activities, corroborating part of their medicinal uses. In addition, certain species produce edible fruits and a kind of "butter" with economic importance. All species produce exudate, which often has great relevance in the daily lives of local people. CONCLUSION: Several species of Symphonieae have potential therapeutic applications and some of them have been investigated to scientifically validate their popular uses. In addition, a number of species have proved to be a rich source of promising pharmacologically active compounds. Finally, the value of fruits, exudate and butter, for instance, should serve as a stimulus for the sustainable development of products that aim to take advantage of these natural resources.
Assuntos
Clusiaceae/química , Medicina Tradicional/métodos , Extratos Vegetais/farmacologia , Animais , Etnobotânica , Etnofarmacologia , Humanos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/químicaRESUMO
Plants that produce secondary metabolites with allelopathic activity or phytotoxicity can be biotechnologically important, serving as sources of allelochemicals, and thus contributing to the agroindustrial sector. Vismia japurensis (Hypericaceae) is an Amazonian species that grows in clumps called vismiais, from which most other plants are absent. Accordingly, the objective of this study was to identify possible phytotoxicity effects of hexane and methanol extracts of Vismia japurensis leaves and branches in vivo and from seedlings grown in vitro on Lactuca sativa. In addition, fresh and dry leaves were assayed by the sandwich method in order to determine their ability to release allelochemicals. The hexanic extract from in vitro seedlings reduced germination by 10%, while the methanol extract produced a 16% reduction in germination speed. Root growth of Lactuca sativa was inhibited by 64.7% when subjected to hexane leaf extract, by 39.3% under the influence of hexane branch extract, and by 96.09% for in vitro seedling hexanic extract. When analysed by thin layer chromatography and 1H nuclear magnetic resonance, extracts showed evidence of terpenes, anthraquinones and flavonoids, with greater intensity of signals in the aromatic region of in vitro seedling hexanic extract. Clearly, Vismia japurensis has a high biotechnological potential in terms of the production of substances of low polarity with capacity to interfere in plant development.
Plantas que produzem metabólitos secundários com atividade alelopática ou fitotóxica podem ser biotecnologicamente importantes, servindo como fontes de aleloquímicos e, assim, contribuindo para o setor agroindustrial. Vismia japurensis (Hypericaceae) é uma espécie amazônica que cresce em grupos, formando vismiais. Assim, o objetivo deste estudo foi identificar possíveis efeitos fitotóxicos de extratos hexânicos e metanólicos de folhas e ramos de Vismia japurensis in vivo e de plântulas cultivadas in vitro sobre Lactuca sativa. Além disso, folhas frescas e secas foram analisadas pelo método sanduíche, a fim de determinar sua capacidade de liberação de aleloquímicos. O extrato hexânico de plântulas in vitro reduziu a germinação em 10% e o extrato metanólico promoveu uma redução de 16% na velocidade de germinação. O crescimento radicular de Lactuca sativa foi inibido em 64,7% quando submetido ao extrato hexânico das folhas, em 39,3% sob influência do extrato hexânico dos galhos e em 96,09% para o extrato de hexânico das plântulas in vitro. Quando analisados por cromatografia em camada delgada e ressonância magnética nuclear de 1H, os extratos mostraram evidências de terpenos, antraquinonas e flavonoides, com maior intensidade de sinais na região aromática do extrato hexânico das plântulas in vitro. Assim, Vismia japurensis possui elevado potencial biotecnológico em termos de produção de substâncias de baixa polaridade com capacidade de interferência no desenvolvimento de plantas.
Assuntos
Lactuca/efeitos dos fármacos , Antraquinonas , Clusiaceae/química , Clusiaceae/toxicidade , Terpenos , Técnicas In VitroRESUMO
Bacuri (Platonia insignis Mart) is a species from the Clusiaceae genus. Its fruit pulp is commonly used in South America in several food products, such as beverages, ice cream and candies. Only the pulp of the fruit is used, and the peels and seeds are considered waste from these industries. As a trioxygenated xanthone source, this species is of high interest for bioproduct development. This work evaluated the mesocarp and epicarp of bacuri fruits through different extraction methods and experimental conditions (pH, temperature and solvent) in order to determine the most effective method for converting this agro-industrial waste in a value-added bioproduct. Open-column procedures and HPLC and NMR experiments were performed to evaluate the chemical composition of the extracts, along with total phenols, total flavonoids and antioxidant activities (sequestration of the DPPH and ABTS radicals). A factorial design and response surface methodology were used. The best extraction conditions of substances with antioxidant properties were maceration at 50 °C with 100% ethanol as solvent for mesocarp extracts, and acidic sonication in 100% ethanol for epicarp extracts, with an excellent phenolic profile and antioxidant capacities. The main compounds isolated were the prenylated benzophenones garcinielliptone FC (epicarp) and 30-epi-cambogin (mesocarp). This is the first study analysing the performance of extraction methods within bacuri agro-industrial waste. Results demonstrated that shells and seeds of bacuri can be used as phenolic-rich bioproducts obtained by a simple extraction method, increasing the value chain of this fruit.
Assuntos
Clusiaceae/química , Flavonoides/química , Resíduos Industriais/análise , Antioxidantes/química , Cromatografia Líquida de Alta Pressão , Etanol/química , Frutas/química , Espectroscopia de Ressonância Magnética , Terpenos/química , Triterpenos/químicaRESUMO
Cratoxylum formosum ssp. pruniflorum (Kurz) Gogelein (CP) is an indigenous plant found mainly in southeast Asia. Several in vitro studies have confirmed its activity against hepatocellular carcinoma; however, in vivo studies of the effect of CP on liver cancer are needed. This study investigated the effect of CP on early-stage hepatocarcinogenesis in rat liver when using diethylnitrosamine (DEN) as a carcinogen. Immunohistochemistry was used to detect (a) upregulation of glutathione S-transferase placental (GST-P) positive foci, (b) the proliferating cell nuclear antigen PCNA, and (c) apoptotic cells in the liver as indicators of early-stage carcinogenesis. Immunohistochemical parameters were observed in rats given CP orally following DEN injection. Rats given DEN presented overexpression of GST-P positive foci, PCNA, and apoptotic cells, indicating the formation of cancerous tissues, and these effects were diminished by CP treatment. CP thus inhibited hepatocarcinogenic effects in an animal model. These results could help plan further in vivo studies and support the use of CP to prevent processes that promote the pathogenesis of hepatocellular carcinoma in humans.
Assuntos
Anticarcinógenos/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Clusiaceae/química , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Animais , Carcinógenos/farmacologia , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/metabolismo , Dietilnitrosamina/farmacologia , Glutationa Transferase/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas Experimentais/induzido quimicamente , Neoplasias Hepáticas Experimentais/metabolismo , Masculino , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos WistarRESUMO
BACKGROUND: Drugs currently used for controlling onchocerciasis and lymphatic filariasis (LF) are mainly microfilaricidal, with minimal or no effect on the adult worms. For efficient management of these diseases, it is necessary to search for new drugs with macrofilaricidal activities that can be used singly or in combination with existing ones. Daniellia oliveri and Psorospermum febrifugum are two plants commonly used in the local management of these infections in Bambui, a township in the North West Region of Cameroon, but there is currently no documented scientific evidence to support their claimed anthelmintic efficacy and safety. The aim of this study was to provide evidence in support of the search for means to eliminate these diseases by screening extracts and chromatographic fractions isolated from these plants for efficacy against the parasitic roundworms Onchocerca ochengi and Brugia pahangi. METHODS: The viability of O. ochengi adult worms was assessed using the MTT/formazan assay. Fully confluent monkey kidney epithelial cells (LLC-MK2) served as the feeder layer for the O. ochengi microfilariae (mfs) assays. Viability of the mfs was assessed by microscopic examination for mean motility scoring (relative to the negative control) every 24 h post addition of an extract. The Worminator system was used to test the effects of the extracts on adult B. pahangi motility, and mean motility units were determined for each worm. Cytotoxicity of the active extracts on N27 cells was assessed using the MTS assay. RESULTS: Extracts from D. oliveri and P. febrifugum were effective against the adult roundworms O. ochengi and B. pahangi. Interestingly, extracts showing macrofilaricidal activities against O. ochengi also showed activity against O. ochengi mfs. The hexane stem bark extract of D. oliveri (DOBHEX) was more selective for adult O. ochengi than for mfs, with a half maximal and 100% inhibitory concentration (IC50 and IC100, respectively) against adult O. ochengi of 13.9 and 31.3 µg/ml, respectively. The in vitro cytotoxicity of all active extracts on N27 cells showed selective toxicity for parasites (selectivity index > 1). Bioassay-guided fractionation of the extracts yielded fractions with activity against adult B. pahangi, thus confirming the presence of bioactive principles in the plant extracts. CONCLUSIONS: Our study supports the use of D. oliveri and P. febrifugum in the traditional treatment of onchocerciasis and LF. The further purification of active extracts from these plants could yield lead compounds for filarial drug discovery and development.
Assuntos
Clusiaceae/química , Fabaceae/química , Filaricidas/farmacologia , Onchocerca/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Camarões , Linhagem Celular , Haplorrinos , Humanos , Onchocerca/crescimento & desenvolvimento , Oncocercose/tratamento farmacológico , Oncocercose/parasitologia , Casca de Planta/químicaRESUMO
Allanblackia floribunda has been used to treat an upset stomach in African traditional medicine, but its efficacy and safety have not been scientifically studied. The present research is aimed at assessing the antiulcer property of the seed extract of the plant to validate its traditional claim. Rats were pretreated with three doses of aqueous extract of A. floribunda (AFE) at 30, 100, and 300 mg/kg or omeprazole 10 mg/kg for 1 hr before the acute gastric ulcer was induced by oral administration of 5 mL/kg of 98% ethanol. The animals were sacrificed under anesthesia, and the stomach and blood were collected. The gross histology of the stomach, percentage protection conferred by the treatment, gastric pH, and serum TNF-α and INF-γ were assessed as well as the expression of Ki67 antigens. The antioxidant properties as well as the acute toxicity profile of the plant extract were also assessed. The results show that A. floribunda conferred significant protection on the rats against gastric ulceration with % protection of 46.15, 57.69, and 65.38 for AFE 30, 100, and 300 mg/kg, respectively, as well as 69.23% for omeprazole 10 mg/kg. The plant extract caused marked reductions in gastric pH, TNF-α, and INF-γ with statistical significance (p < 0.001) for AFE 300 mg/kg and omeprazole 10 mg/kg. Also, the plant showed good antioxidant activity comparable to gallic acid. Furthermore, the plant extract modulated the expression of Ki67 antigens. All animals survived the 14-day delayed toxicity test with no significant differences in physical, hematological, and biochemical parameters between rats orally administered with supratherapeutic doses of AFE (5000 mg/kg) or normal saline. The study established that the gastroprotective effect of the seed extract of A. floribunda is attributable to its antisecretory, antioxidant, and anti-inflammatory properties. Additionally, the plant was found to promote ulcer healing via the modulation of the expression Ki67 and was safe at supratherapeutic doses.
Assuntos
Clusiaceae/química , Etanol/toxicidade , Interferon gama/metabolismo , Antígeno Ki-67/metabolismo , Sementes/química , Úlcera Gástrica/tratamento farmacológico , Fator de Necrose Tumoral alfa/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Quelantes/farmacologia , Modelos Animais de Doenças , Sequestradores de Radicais Livres , Concentração Inibidora 50 , Masculino , Óxido Nítrico/metabolismo , Fitoterapia , Picratos/química , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamenteRESUMO
A new dihydrochromene derivative, named lisofurvin (1) and a xanthone, named dihydrobrasixanthone B (2) together with twenty one known compounds (3-23) were isolated from propolis of the stingless bee Lisotrigona furva. Their chemical structures were determined by means of spectroscopic methods including 1D and 2D NMR, and MS. The chemical constituents are predominantly geranyl(oxy) xanthones and Cratoxylum cochinchinense was suggested as a resin source, besides two other plants Mangifera indica and dammar trees (Dipterocarpaceae). Compound 1 showed significant cytotoxic activity against KB, HepG-2, and Lu-1 cancer cell lines with IC50 values range from 12.63 to 15.17 µg/mL. Several isolated compounds were active against one to four tested cancer cell lines. In addition, among the isolated compounds, α-mangostin (15) displayed the strongest antimicrobial activity against three Gram (+) strains, P. aeruginosa, and C. albicans with MIC values ranging between 1 and 2 µg/mL. Compound 22 showed good activity against three Gram (+) strains and C. albicans.
Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Própole/química , Xantonas/farmacologia , Animais , Anti-Infecciosos/isolamento & purificação , Antineoplásicos/isolamento & purificação , Abelhas , Linhagem Celular Tumoral , Clusiaceae/química , Dipterocarpaceae/química , Humanos , Mangifera/química , Estrutura Molecular , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Vietnã , Xantonas/isolamento & purificaçãoRESUMO
Osteoarthritis has become one of the main diseases affecting the life of many elderly people with high incidence of disability, and local chronic inflammation in the joint cavity is the most crucial pathological feature of osteoarthritis. Astilbin is the main active component in a variety of natural plants such as Hypericum perforatum and Sarcandra glabra, which possess antioxidant and anti-inflammatory effects. At present, there is no study about the protective effect of Astilbin for osteoarthritis. The purpose of this study was to investigate the effect of Astilbin in human OA chondrocytes and mouse OA model, which was established by surgery-mediated destabilization of the medial meniscus (DMM). In vitro, we found that Astilbin pre-treatment inhibited lipopolysaccharide (LPS)-induced overproduction of inflammation-correlated cytokines such as nitric oxide (NO), prostaglandin E2 (PGE2), tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and suppressed overexpression of inflammatory enzymes such as inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2). Astilbin, on the other hand, prevented the LPS-induced degradation of extracellular matrix (ECM) by down-regulating MMP13 (matrix metalloproteinases 13) and ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5). Moreover, by inhibiting the formation of the TLR4/MD-2/LPS complex, Astilbin blocked LPS-induced activation of TLR4/NF-κB signalling cascade. In vivo, Astilbin showed the chondro-protective effect in the surgical-induced OA mouse models. In conclusion, our findings provided evidence that develops Astilbin as a potential therapeutic drug for OA patients.
Assuntos
Flavonóis/farmacologia , Antígeno 96 de Linfócito/metabolismo , Osteoartrite/metabolismo , Receptor 4 Toll-Like/metabolismo , Idoso , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/metabolismo , Condrócitos/metabolismo , Clusiaceae/química , Dinoprostona/metabolismo , Matriz Extracelular/metabolismo , Feminino , Humanos , Inflamação , Interleucina-6/metabolismo , Lipopolissacarídeos , Masculino , Camundongos , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Osteoartrite/prevenção & controle , Extratos Vegetais/farmacologia , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Five isolated xanthones from the C. cochinchinense and G. mangostana were evaluated and tested for antibacterial activities. Isolated 4 and 5 exhibited potent anti-MRSA and P. aeruginosa activity, but showed poor pharmacokinetic properties via ADMET prediction. It led us to improve pharmacokinetic properties of 4 and 5 by partially modifying them in acidic condition yielding fourteen analogues. It was found that analogues 4b, 4d and 5b possessed proper pharmacokinetic properties, while only 4b exhibited the best anti-MRSA and P. aeruginosa activity. The SEM results indicated that 4b may interact with or damage the cell wall of MRSA and P. aeruginosa. Moreover, a combination of 4b and vancomycin exhibits synergistic effect against both MRSA and P. aeruginosa at MIC value of 4.98 (MIC = 18.75 µg/mL for 4b) and 9.52 µg/mL (MIC = 75 µg/mL for 4b), respectively.
Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Vancomicina/farmacologia , Xantonas/farmacologia , Antibacterianos/química , Antibacterianos/isolamento & purificação , Clusiaceae/química , Relação Dose-Resposta a Droga , Garcinia mangostana/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Relação Estrutura-Atividade , Vancomicina/química , Xantonas/química , Xantonas/isolamento & purificaçãoRESUMO
Cratoxylum formosum Dyer is a medicinal plant widely found in Asia and commonly consumed for food and folk medicine. It is rich in phenolic compounds. The present study utilized water crude extract of C. formosum leaves to synthesize zinc oxide nanoparticles (ZnO NPs) by green synthesis. The synthesized ZnO NPs with the average electronic band gap â¼3⯠eV were obtained and found to either have spherical shape or sheet-like structures depending on synthesis process and concentration of crude extract. Higher concentration of C. formosum extract also eliminates impurity of Zn(OH)2 during the synthesis. Results from an agar disk diffusion assay demonstrated that all synthesized ZnO samples inhibited growth of Gram-positive bacteria, Bacillus subtilis and Staphylococcus epidermidis and Gram-negative bacterium, Escherichia coli. Furthermore, all synthesized ZnO demonstrated potent anti-cancer activity against non-melanoma skin cancer cells (A431) and the intermediary of cancerous keratinocytes (HaCaT) without affecting normal cell lines (Vero). In addition, we observed that the ZnO nanosheet offered stronger cytotoxicity effects against A431 than spherical shaped ZnO particles. Analysis of RNA-sequencing data revealed that synthesized ZnO nanosheets altered the number of genes in pathways involved in cancer and MAPK signaling pathways in A431 cells. Several isoforms of metallothionein transcripts were upregulated including transcripts involved in inflammatory responses whereas transcripts promoted cell proliferation and apoptosis were downregulated. Therefore, these studies firstly reported potential usage of the green-synthesized ZnO nanosheets from C. formosum extract for development of antibacterial substances or anticancer drugs.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Clusiaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Neoplasias Cutâneas/tratamento farmacológico , Óxido de Zinco/síntese química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Linhagem Celular Tumoral , Chlorocebus aethiops , Química Verde , Humanos , Queratinócitos/efeitos dos fármacos , Nanopartículas Metálicas , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Células VeroRESUMO
The Brazilian red propolis (BRP) constitutes an important commercial asset for northeast Brazilian beekeepers. The role of Dalbergia ecastaphyllum (L.) Taub. (Fabaceae) as the main botanical source of this propolis has been previously confirmed. However, in addition to isoflavonoids and other phenolics, which are present in the resin of D. ecastaphyllum, samples of BRP are reported to contain substantial amounts of polyprenylated benzophenones, whose botanical source was unknown. Therefore, field surveys, phytochemical and chromatographic analyses were undertaken to confirm the botanical sources of the red propolis produced in apiaries located in Canavieiras, Bahia, Brazil. The results confirmed D. ecastaphyllum as the botanical source of liquiritigenin (1), isoliquiritigenin (2), formononetin (3), vestitol (4), neovestitol (5), medicarpin (6), and 7-O-neovestitol (7), while Symphonia globulifera L.f. (Clusiaceae) is herein reported for the first time as the botanical source of polyprenylated benzophenones, mainly guttiferone E (8) and oblongifolin B (9), as well as the triterpenoids ß-amyrin (10) and glutinol (11). The chemotaxonomic and economic significance of the occurrence of polyprenylated benzophenones in red propolis is discussed.
Assuntos
Clusiaceae/química , Dalbergia/química , Isoflavonas/química , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/química , Benzofenonas/análise , Benzofenonas/química , Brasil , Chalconas/análise , Cromatografia Líquida de Alta Pressão , Desenho de Fármacos , Flavanonas/análise , Flavonoides/análise , Isoflavonas/análise , Espectroscopia de Ressonância Magnética , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/análise , Extratos Vegetais/análise , Pterocarpanos/análise , Terpenos/análise , Triterpenos/análiseRESUMO
The aim of the present study was to evaluate the diuretic effect of 1,3,5,6-tetrahydroxyxanthone (THX), isolated from preparations of Garcinia achachairu Rusby (Clusiaceae) branches, in rats. Wistar normotensive (NTR) and spontaneously hypertensive rats (SHR) received a single oral treatment with THX, hydrochlorothiazide (HCTZ) or just vehicle (VEH). The effects of THX in combination with diuretics of clinical use, as well as with l-NAME, atropine, and indomethacin were also explored. Cumulative urine volume and urinary parameters were measured at the end of the 8-h or 24-h experiment. THX was able to stimulate 8-h and 24-h diuresis in both NTR and SHR, as well as urinary Na+ and K+ excretion, at a dose of 0.1â¯mg/kg; while 8-h urinary Cl- levels were only significantly increased in the group of animals treated with THX at the dose of 0.3â¯mg/kg. In addition, Ca2+ content was reduced in the 24-h urine of THX-treated NTR and SHR, like that obtained in the HCTZ (10â¯mg/kg) group. The combination with HCTZ or furosemide, but not with amiloride, significantly enhanced THX-induced diuresis. The diuretic effect with HCTZ plus THX treatment was accompanied by an increase of the urinary Na+, K+, and Cl- excretion. On the other hand, when given THX in combination with amiloride, there was a significant increase in Na+ and a decrease in K+ excretion, an effect characteristic of this class of diuretics. Moreover, the diuretic effect of THX was heightened after pretreatment with l-NAME, and its ability to induce diuresis was prevented neither in the presence of indomethacin nor in the presence of atropine. However, the pretreatment with atropine completely avoided the saluretic effect stimulated by THX, suggesting, at least in part, the role of muscarinic receptors in the renal effects of THX disclosed in this study.
Assuntos
Diurese/efeitos dos fármacos , Hipertensão/tratamento farmacológico , Xantonas/farmacologia , Animais , Atropina/farmacologia , Clusiaceae/química , Clusiaceae/metabolismo , Feminino , Hidroclorotiazida/farmacologia , NG-Nitroarginina Metil Éster/farmacologia , Potássio/urina , Ratos , Ratos Endogâmicos SHR , Ratos Wistar , Sódio/urina , Xantonas/uso terapêuticoRESUMO
Our recent study reported that multidrug-resistant (MDR) human A549 lung cancer cells (A549RT-eto) with the elevated expression of NF-κB showed epithelial-mesenchymal transition (EMT), increasing spheroid formation and elevating the expression levels of stemness-related factors, including Oct4, Nanog, Sox2, Bmi1, and Klf4. Therefore, when new therapeutic agents targeting these malignant cancer cells were explored, we found that caged-xanthone (CX) isolated from the roots of Cratoxylum formosum ssp. pruniflorum diminished the expression of NF-κB, P-glycoprotein (P-gp) protein levels, cell migration and invasion, and sphere-forming ability of A549RT-eto cells. To address the role of NF-κB in these malignant cancer features, we treated A549RT-eto cells with NF-κB siRNAs in the present work. We found that the knockdown of NF-κB inhibited EMT and sphere formation. Furthermore, co-treatment with CX and NF-κB siRNA accelerated the death of apoptotic cells through the decrease of P-gp protein levels. These results suggest that NF-κB was involved in malignant cancer phenotypes and MDR in A549RT-eto cells. Taken together, our findings suggest that CX can be a potential therapeutic agent for the treatment of malignant tumor cells.
Assuntos
Antineoplásicos/farmacologia , Clusiaceae/química , Subunidade p50 de NF-kappa B/metabolismo , Xantonas/farmacologia , Células A549 , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Regulação para Baixo , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Humanos , Fator 4 Semelhante a Kruppel , Subunidade p50 de NF-kappa B/genéticaRESUMO
Allanblackia genus, an endless source of bioactive compounds, was investigated for its antibacterial properties. The chemical study of the methanol extract from the fruits of Allanblackia gabonensis resulted in the isolation of the undescribed guttiferone BL (1) along with the known kaempferol (2), morelloflavone (3), morelloflavone 7â³-O-ß-D-glucopyranoside (4), ß-sitosterol 3-O-ß-D-glucopyranoside and ß-sitosterol. Their structures were determined using spectrometry and spectroscopic techniques. The antibacterial activity was evaluated against five Gram-negative and two Gram-positive strains using a broth micro-dilution method. Compounds displayed low to significant activity against the tested bacterial strains with MICs ranging from 8 to 512 µg/mL. Morelloflavone (3) presented significant activity against E. coli ATCC8739 (MIC = 8 µg/mL) while guttiferone BL (1) exhibited low activity (MICs = 256-512 µg/mL) against all the tested strains. The crude extract also had moderate to significant activity against the tested bacterial strains.
Assuntos
Antibacterianos/farmacologia , Benzofenonas/farmacologia , Clusiaceae/química , Antibacterianos/química , Benzofenonas/isolamento & purificação , Biflavonoides/isolamento & purificação , Biflavonoides/farmacologia , Avaliação Pré-Clínica de Medicamentos/métodos , Escherichia coli/efeitos dos fármacos , Frutas/química , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Quempferóis/isolamento & purificação , Quempferóis/farmacologia , Metanol/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
Two novel ß-diketones, 2,6,9-trimethyl-8-decene-3,5-dione (A) and 3,7,10-trimethyl-9-undecene-4,6-dione (B), were identified from the renowned medicinal plant Hypericum perforatum L. The structures of ß-diketones A and B were corroborated by syntheses (4 steps starting from methyl acetoacetate, overall yields 30% and 23%, respectively). In solution, these ß-diketones predominantly exist as two rapidly interconverting ß-keto-enol tautomers. The structures of A and B show some common fragments with the molecules of hyperforin and adhyperforin, respectively, the acknowledged multi-target secondary metabolites from St. John's wort. It is therefore not surprising that A displayed a noteworthy biological activity profile as well (including brine shrimp toxicity, antinociceptive, antidepressant and acetylcholinesterase inhibitory activity). ß-Diketone A manifested the most outstanding potency as an acetylcholinesterase inhibitor with IC50 value of 1.51⯵M pointing again to the ß-keto-enol moiety as a promising lead structure for the development of drugs that could lessen symptoms of Alzheimer's disease (such as dementia, depression and pain).
Assuntos
Clusiaceae/metabolismo , Cetonas/metabolismo , Analgésicos/farmacologia , Animais , Antidepressivos/farmacologia , Artemia/efeitos dos fármacos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Inibidores da Colinesterase/farmacologia , Clusiaceae/química , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Concentração Inibidora 50 , Cetonas/química , Cetonas/farmacologia , Prenilação , Espectroscopia de Prótons por Ressonância MagnéticaRESUMO
Four new caged xanthones (1-4) and two known compounds (5, 6) were isolated from the roots of Cratoxylum cochinchinense, a polyphenol rich plant, collected in China. The structures of the isolated compounds (1-6) were characterized by obtaining their detailed spectroscopic data. In particular, compounds 1 and 6 were fully identified by X-ray crystallographic data. The isolated compounds (1-6) were evaluated against protein tyrosine phosphatase 1B (PTP1B), which plays an important role in diabetes, obesity, and cancer. Among these compounds, 3, 4, and 6 displayed significant inhibition with IC50 values of 76.3, 43.2, and 6.6⯵M, respectively. A detailed kinetic study was conducted by determining Km, Vmax, and the ratio of Kik and Kiv, which revealed that all the compounds behaved as competitive inhibitors.