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1.
Mol Phylogenet Evol ; 186: 107837, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37270033

RESUMO

This molecular study of the Neotropical Artocarpeae, the closest living allies of the Asia-Pacific breadfruit genus, uses phylogenomic and network analyses to untangle the evolutionary history of this difficult group. Results paint a picture of a rapid radiation, with introgression, incomplete lineage sorting, and lack of gene tree resolution confounding attempts to reconstruct a well-supported bifurcating tree. While coalescent-based species trees were markedly at odds with morphology, multifurcating phylogenetic network analyses recovered multiple histories, with clearer traces of morphological alliances. The sole unambiguous finding is the sister relationship between Clarisia sect. Acanthinophyllum and the rest of the Neotropical Artocarpeae; as a result, the genus Acanthinophyllum is reinstated.


Assuntos
Moraceae , Filogenia , Evolução Biológica , Ásia
2.
J Nat Prod ; 86(4): 1010-1018, 2023 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-37043719

RESUMO

Three new benzo[b]naphtho[2,1-d]furans, usambarins A-C (1-3), five new 2-phenylnaphthalenes, usambarins D-H (4-8), a new flavan (9), and a new phenyl-1-benzoxepin (10) as well as two known compounds (11 and 12) were isolated from the extract of the stem and roots of Streblus usambarensis (Moraceae). The structures were deduced using NMR spectroscopic and mass spectrometric analyses, and those of compounds 1 and 4 were confirmed by X-ray crystallography. Usambarin D (4) demonstrated moderate antibacterial activity (MIC 9.0 µM) against Bacillus subtilis, while none of the tested compounds were effective against Escherichia coli.


Assuntos
Furanos , Moraceae , Furanos/farmacologia , Furanos/química , Antibacterianos/química , Raízes de Plantas , Moraceae/química , Estrutura Molecular , Testes de Sensibilidade Microbiana
3.
Molecules ; 28(21)2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37959718

RESUMO

Neuroinflammation activated by microglia affects inflammatory pain development. This study aimed to explore the anti-inflammatory properties and mechanisms of 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3-methoxyxanthone (THMX) from Cudrania tricuspidata in microglia activation-mediated inflammatory pain. In RAW 264.7 and BV2 cells, THMX has been shown to reduce lipopolysaccharide (LPS)-induced inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and pro-inflammatory mediators and cytokines, including nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-6, and tumor necrosis factor alpha (TNF-α). THMX also decreased LPS-induced phosphorylation of mitogen-activated protein kinase (MAPK) and the activation of p65 nuclear factor kappa B (NF-κB). Interestingly, THMX also activated heme oxygenase (HO)-1 expression. These findings suggest that THMX is a promising biologically active compound against inflammation through preventing MAPKs and NF-ĸB and activating HO-1 signaling pathways.


Assuntos
Moraceae , NF-kappa B , NF-kappa B/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/metabolismo , Transdução de Sinais , Microglia/metabolismo , Interleucina-6/metabolismo , Dor/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo
4.
Bioorg Chem ; 127: 106004, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35843015

RESUMO

Cardiac glycosides (CGs) show potential broad-spectrum antiviral activity by targeting cellular host proteins. Herein are reported the isolation of five new (1-5) and eight known (7-13) CGs from the roots of Streblus asper Lour. Of these compounds 1 and 7 exhibited inhibitory action against EBV early antigen (EA) expression, with half-maximal effective concentration values (EC50) being less than 60 nM, and they also showed selectivity, with selectivity index (SI) values being 56.80 and 103.17, respectively. Preliminary structure activity relationships indicated that the C-10 substituent, C-5 hydroxy groups, and C-3 sugar unit play essential roles in the mediation of the inhibitory activity of CGs against EBV. Further enzyme experiments demonstrated that these compounds might inhibit ion pump function and thereby change the intracellular signal transduction pathway by binding to Na+/K+-ATPase, as validated by simulated molecular docking. This study is the first report that CGs can effectively limit EBV lytic replication, and the observations made in this study may be of value for lead compound development.


Assuntos
Glicosídeos Cardíacos , Infecções por Vírus Epstein-Barr , Moraceae , Glicosídeos Cardíacos/química , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Herpesvirus Humano 4/metabolismo , Simulação de Acoplamento Molecular , Moraceae/química
5.
J Plant Res ; 135(2): 203-220, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35080694

RESUMO

Species of Broussonetia have been essential in the development of papermaking technology. In Japan and Korea, a hybrid between B. monoica and B. papyrifera (= B. × kazinoki) known as kozo and daknamu is still the major source of raw materials for making traditional paper washi and hanji, respectively. Despite their cultural and practical significance, however, the origin and taxonomy of kozo and daknamu remain controversial. Additionally, the long-held generic concept of Broussonetia s.l., which included Sect. Allaeanthus and Sect. Broussonetia, was challenged as phylogenetic analyses showed Malaisia is sister to the latter section. To re-examine the taxonomic proposition that recognizes Allaeanthus, Broussonetia, and Malaisia (i.e., Broussonetia alliance), plastome and nuclear ribosomal DNA (nrDNA) sequences of six species of the alliance were assembled. Characterized by the canonical quadripartite structure, genome alignments and contents of the six plastomes (160,121-162,594 bp) are highly conserved, except for the pseudogenization and/or loss of the rpl22 gene. Relationships of the Broussonetia alliance are identical between plastome and nrDNA trees, supporting the maintenance of Malaisia and the resurrection of Allaeanthus. The phylogenomic relationships also indicate that the monoecy in B. monoica is a derived state, possibly resulting from hybridization between the dioecious B. kaempferi (♀) and B. papyrifera (♂). Based on the hypervariable ndhF-rpl32 intergenic spacer selected by sliding window analysis, phylogeographic analysis indicates that B. monoica is the sole maternal parent of B. × kazinoki and that daknamu carries multiple haplotypes, while only one haplotype was detected in kozo. Because hybridizations between B. monoica and B. papyrifera are unidirectional and have occurred rarely in nature, our data suggest that daknamu might have originated via deliberate hybrid breeding selected for making hanji in Korea. On the contrary, kozo appears to have a single origin and the possibility of a Korean origin cannot be ruled out.


Assuntos
Broussonetia , Moraceae , Broussonetia/química , Broussonetia/genética , Filogenia , Filogeografia , Melhoramento Vegetal
6.
Molecules ; 27(14)2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35889459

RESUMO

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-ß-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-ß-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-ß-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-ß-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-ß-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.


Assuntos
Furocumarinas , Moraceae , Vitiligo , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina/química , Animais , Varredura Diferencial de Calorimetria , Permeabilidade , Extratos Vegetais/farmacologia , Ratos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X , beta-Ciclodextrinas/química
7.
Molecules ; 27(22)2022 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-36431822

RESUMO

Antiaris africana Engler leaves have been used in Senegalese folk medicine to treat breast cancer. The present study aimed to investigate the anticancer potential of Antiaris africana Engler leaves using several human cancer cell lines. The leaves of Antiaris africana Engler were extracted in parallel with water or 70% ethanol and each extract divided into three parts by successive liquid-liquid extraction with ethyl acetate and butanol. The phytochemical components of the active extract were investigated using ultra-performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry (UPLC-DAD-QTOF-MS/MS). The cytotoxic and cytostatic effects of each extract, as well as their fractions, were evaluated in vitro via flow and image cytometry on different human cancer phenotypes, such as breast (MCF-7), pancreas (AsPC-1), colon (SW-620) and acute monocytic leukemia (THP-1). Both hydro-alcoholic and aqueous extracts induced strong apoptosis in MCF-7 cells. The water fraction of the hydro-alcoholic extract was found to be the most active, suppressing the cell growth of MCF-7 in a dose-dependent manner. The half maximum effective concentration (EC50) of this fraction was 64.6 ± 13.7 µg/mL for MCF-7, with equivalent values for all tested phenotypes. In parallel, the apoptotic induction by this fraction resulted in a EC50 of 63.5 ± 1.8 µg/mL for MCF-7, with again equivalent values for all other cellular tested phenotypes. Analysis of this fraction by UPLC-DAD-QTOF-MS/MS led to the identification of hydroxycinnamates as major components, one rutin isomer, and three cardiac glycosides previously isolated from seeds and bark of Antiaris africana Engler and described as cytotoxic in human cancer models. These results provide supportive data for the use of Antiaris africana Engler leaves in Senegal.


Assuntos
Antiaris , Moraceae , Criança , Humanos , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão/métodos , Extratos Vegetais/química , Folhas de Planta/química , Água/análise
8.
Molecules ; 27(16)2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36014582

RESUMO

The Broussonetia genus (Moraceae), recognized for its value in many Chinese traditional herbs, mainly includes Broussonetia papyrifera (L.) L'Hér. ex Vent. (BP), Broussonetia kazinoki Siebold (BK), and Broussonetia luzonica (Blanco) Bureau (BL). Hitherto, researchers have found 338 compounds isolated from BP, BK, and BL, which included flavonoids, polyphenols, phenylpropanoids, alkaloids, terpenoids, steroids, and others. Moreover, its active compounds and extracts have exhibited a variety of pharmacological effects such as antitumor, antioxidant, anti-inflammatory, antidiabetic, anti-obesity, antibacterial, and antiviral properties, and its use against skin wrinkles. In this review, the phytochemistry and pharmacology of Broussonetia are updated systematically, after its applications are first summarized. In addition, this review also discusses the limitations of investigations and the potential direction of Broussonetia. This review can help to further understand the phytochemistry, pharmacology, and other applications of Broussonetia, which paves the way for future research.


Assuntos
Alcaloides , Broussonetia , Moraceae , Broussonetia/química , Etnofarmacologia , Flavonoides/farmacologia , Compostos Fitoquímicos/química , Extratos Vegetais/química
9.
Molecules ; 27(24)2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36558142

RESUMO

Tyrosinase is a multifunctional, copper-containing and rate-limiting oxidase that catalyses crucial steps in the melanogenesis pathway and is responsible for skin-pigmentation abnormalities in mammals. Numerous tyrosinase inhibitors derived from natural and synthetic sources have been identified as an objective for the development of anti-melanogenesis agents. However, due to side effects and lack of expected efficiency, only a small percentage of them are used for medical and cosmetic purposes. This critical review focuses on searching for novel active substances and recently discovered plant-derived anti-tyrosinase inhibitors from the Morus genus (Moraceae family). A detailed analysis of their structure-activity relationships is discussed. The information contained in this article is crucial for the cosmetics and medical industries, in order to show new directions for the effective search for natural anti-melanogenesis products (with satisfactory efficiency and safety) to treat and cure hyperpigmentation.


Assuntos
Moraceae , Morus , Animais , Morus/metabolismo , Inibidores Enzimáticos/farmacologia , Relação Estrutura-Atividade , Pele/metabolismo , Monofenol Mono-Oxigenase , Melaninas/metabolismo , Mamíferos/metabolismo
10.
Am J Bot ; 108(9): 1793-1807, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34519027

RESUMO

PREMISE: The mechanisms generating the geographical distributions of genetic diversity are a central theme in evolutionary biology. The amount of genetic diversity and its distribution are controlled by several factors, including dispersal abilities, physical barriers, and environmental and climatic changes. We investigated the patterns of genetic diversity and differentiation among populations of the widespread species Brosimum alicastrum in Mexico. METHODS: Using nuclear DNA microsatellite data, we tested whether the genetic structure of B. alicastrum was associated with the roles of the Trans-Mexican Volcanic Belt and the Isthmus of Tehuantepec as geographical barriers to gene flow and to infer the role of past events in the genetic diversity patterns. We further used a maximum-likelihood population-effects mixed model (MLPE) to identify the main factor affecting population differentiation in B. alicastrum. RESULTS: Our results suggested that Mexican B. alicastrum is well differentiated into three main lineages. Patterns of the genetic structure at a finer scale did not fully correspond to the current geographical barriers to gene flow. According to the MLPE mixed model, isolation by distance is the best model for explaining the genetic differentiation of B. alicastrum in Mexico. CONCLUSIONS: We propose that the differentiation patterns might reflect (1) an ancient differentiation that occurred in Central and South America, (2) the effects of past climatic changes, and (3) the functions of some physical barriers to gene flow. This study provides insights into the possible mechanisms underlying the geographic genetic variation of B. alicastrum along a moisture gradient in tropical lowland forests.


Assuntos
Variação Genética , Moraceae , Fluxo Gênico , México , Repetições de Microssatélites/genética
11.
J Nat Prod ; 84(4): 1359-1365, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33826847

RESUMO

Cudraisoflavone J (1), isolated from Cudrania tricuspidata, is a potent neuroprotective compound with a chiral center. Herein, we report the first total synthesis of racemic cudraisoflavone J (1) using a Claisen rearrangement and a Suzuki coupling reaction as the key steps. Racemic secondary alcohol was kinetically resolved to give (+)- and (-)-cudraisoflavone J with up to 97 and 88% enantiomeric excess, respectively. The modified Mosher's method was used to elucidate the absolute configuration of naturally occurring cudraisoflavone J.


Assuntos
Isoflavonas/síntese química , Fármacos Neuroprotetores/síntese química , Estrutura Molecular , Moraceae/química
12.
Bioorg Chem ; 114: 105098, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34153812

RESUMO

Investigation of chemical constituents of Masclura tricuspidata leaves resulted in the isolation of 47 isoflavonoids possessing prenyl groups with different numbers and structures. Among them, sixteen compounds named cudracusisoflavones A-P (1-16) were first isolated from nature. The isoflavonoids isolated from M. tricuspidata leaves showed anti-diabetic effects as measured by inhibition on α-glucosidase activity and advanced glycation end-products (AGEs) formations. Especially, cudracusisoflavone L (12), a new compound, together with gancaonin M (27), erysenegalensein E (41) and millewanin G (44) showed strong α-glucosidase inhibition with IC50 values <10.0 µM. In addition, cudracusisoflavones A (1), D (4), M (13) and N (14), together with known prenylated isoflavonoids efficiently inhibited methylglyoxal (MGO)- or glyoxal (GO)-induced AGE formations. Structure activity relationship together with molecular docking analysis suggested the importance of hydroxy group and linear type of prenyl moiety for α-glucosidase inhibition. Conclusively, diverse prenylated isoflavonoids in M. tricuspidata leaves might ameliorate glycotoxicity-induced metabolic diseases.


Assuntos
Flavonoides/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Inibidores de Glicosídeo Hidrolases/farmacologia , Hipoglicemiantes/farmacologia , Moraceae/química , alfa-Glucosidases/metabolismo , Relação Dose-Resposta a Droga , Flavonoides/química , Flavonoides/isolamento & purificação , Produtos Finais de Glicação Avançada/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosilação/efeitos dos fármacos , Hipoglicemiantes/química , Hipoglicemiantes/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Folhas de Planta/química , Saccharomyces cerevisiae/enzimologia , Relação Estrutura-Atividade
13.
J Plant Res ; 134(5): 1013-1020, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34215965

RESUMO

While increasing numbers of studies report wide variations of leaf silicon (Si) accumulation among plant species, within-species variations of leaf Si accumulation have scarcely been examined for tree species. As in crop plants, environmental factors that affect transpiration rates may influence passive transpiration-dependent transport of Si uptake in trees. Here, we tested a hypothesis that leaf Si accumulation rate should be higher in shoots that receive more light and thus achieve faster growth, using Broussonetia papyrifera, a pioneer tree species with successive leaf production and Si accumulation with leaf age. We marked individual leaves weekly throughout the growing season (June-September), and measured Si concentration and light availability in relation to the chronosequence of leaf age in September. In shoots that continued growing and successively produced leaves throughout the growing season, leaf Si content increased linearly with leaf age. In support of our hypothesis, leaf Si accumulation rate varied widely among shoots with positive correlations with shoot growth and light availability. In conclusion, both leaf age and microenvironment affect within-species variations in leaf Si concentration of this species, a moderate Si accumulator.


Assuntos
Broussonetia , Moraceae , Morus , Folhas de Planta , Silício
14.
Chem Biodivers ; 18(7): e2001068, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33998146

RESUMO

In Brazil, there is a large diversity of species of small edible fruits that are considered sources of nutrients and functional properties. They present a high innovation domain for the pharmaceutical, cosmetic and food industries due to their health-promoting properties. Edible fruits from Brosimum gaudichaudii (Moraceae) are widely consumed and used in folk medicine and in feed by the population of the Brazilian Cerrado. Nevertheless, detailed information on the chemical fingerprint, antiradical activity and safety aspects of these fruits is still unknown. Thus, the aim of this work was to investigate the bioactive compounds of hydroethanolic extracts of fruits from Brosimum gaudichaudii using high-performance liquid chromatography combined with mass spectrometry using electrospray ionization (HPLC ESI-MS). Eighteen different compounds, including flavonoids, coumarins, arylbenzofurans, terpenoids, stilbenes, xanthones and esters, were detected. Moreover, the study indicated that the hydroethanolic extract of fruits from B. gaudichaudii presented low scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radicals (IC50 >800 µg mL-1 ) and was cytotoxic (IC50 <30 µg mL-1 ) in Chinese hamster ovary cells (CHO-K1) by an in vitro assay. This is the first report of the chemical profile, antioxidant activity and cytotoxic properties of the hydroethanolic extract of fruits from B. gaudichaudii.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Moraceae/química , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Brasil , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetulus , Frutas/química , Humanos , Estrutura Molecular , Picratos/antagonistas & inibidores , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Plantas Comestíveis/química
15.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299130

RESUMO

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.


Assuntos
Cisplatino/toxicidade , Frutas/química , Macrófagos/efeitos dos fármacos , Melanoma Experimental/tratamento farmacológico , Moraceae/química , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Antineoplásicos/toxicidade , Apoptose , Proliferação de Células , Feminino , Humanos , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Macrófagos/patologia , Melanoma Experimental/induzido quimicamente , Melanoma Experimental/patologia , Potencial da Membrana Mitocondrial , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Substâncias Protetoras/farmacologia , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Int J Mol Sci ; 22(14)2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34299094

RESUMO

The root bark of Cudrania tricuspidata has been reported to have anti-sclerotic, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and cytotoxic activities. In the present study, the effect of 16 compounds from C. tricuspidata on tumor necrosis factor-α+interferon-γ-treated HaCaT cells were investigated. Among these 16 compounds, 11 decreased IL-6 production and 15 decreased IL-8 production. The six most effective compounds, namely, steppogenin (2), cudraflavone C (6), macluraxanthone B (12), 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3- methoxyxanthone (13), cudraflavanone B (4), and cudratricusxanthone L (14), were selected for further experiments. These six compounds decreased the expression levels of chemokines, such as regulated on activation, normal T cell expressed and secreted (RANTES) and thymus and activation-regulated chemokine (TARC), and downregulated the protein expression levels of intercellular adhesion molecule-1. Compounds 2, 6, 12, 4, and 14 inhibited nuclear factor-kappa B p65 translocation to the nucleus; however, compound 13 showed no significant effects. In addition, extracellular signal regulatory kinase-1/2 phosphorylation was only inhibited by compound 14, whereas p38 phosphorylation was inhibited by compounds 13 and 4. Taken together, the compounds from C. tricuspidata showed potential to be further developed as therapeutic agents to suppress inflammation in skin cells.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Moraceae/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Interferon gama/metabolismo , Queratinócitos/metabolismo , NF-kappa B/metabolismo , Fosforilação , Compostos Fitoquímicos/classificação , Transdução de Sinais , Fator de Necrose Tumoral alfa/farmacologia
17.
Molecules ; 26(19)2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34641629

RESUMO

Psoriasis is a chronic inflammatory skin disease accompanied by excessive keratinocyte proliferation. Corticosteroids, vitamin D3 analogs, and calcineurin inhibitors, which are used to treat psoriasis, have diverse adverse effects, whereas natural products are popular due to their high efficiency and relatively low toxicity. The roots of the Cudrania tricuspidata (C. tricuspidata) are known to have diverse pharmacological effects, among which the anti-inflammatory effect is reported as a potential therapeutic agent in skin cells. Nevertheless, its effectiveness against skin diseases, especially psoriasis, is not fully elucidated. Here, we investigated the effect of cudraxanthone D (CD), extracted from the roots the C. tricuspidata Bureau, on psoriasis using an imiquimod (IMQ)-induced mouse model and the tumor necrosis factor (TNF)-α/interferon (IFN)-γ-activated keratinocytes. IMQ was topically applied to the back skin of C57BL/6 mice for seven consecutive days, and the mice were orally administered with CD. This resulted in reduced psoriatic characteristics, such as the skin thickness and Psoriasis Area Severity Index score, and the infiltration of neutrophils in IMQ-induced skin. CD inhibited the serum levels of TNF-α, immunoglobulin G2a, and myeloperoxidase, and the expression of Th1/Th17 cells in splenocytes. In TNF-α/IFN-γ-activated keratinocytes, CD reduced the expressions of CCL17, IL-1ß, IL-6, and IL-8 by inhibiting the phosphorylation of STAT1 and the nuclear translocation of NF-kB. Taken together, these results suggest that CD could be a potential drug candidate for the treatment of psoriasis.


Assuntos
Anti-Inflamatórios/administração & dosagem , Imiquimode/efeitos adversos , Queratinócitos/citologia , Moraceae/química , Psoríase/tratamento farmacológico , Xantonas/administração & dosagem , Administração Oral , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Modelos Animais de Doenças , Feminino , Humanos , Interferon gama/efeitos adversos , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , NF-kappa B/farmacologia , Extratos Vegetais/química , Raízes de Plantas/química , Psoríase/induzido quimicamente , Psoríase/imunologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/farmacologia , Xantonas/farmacologia
18.
Int J Environ Health Res ; 31(3): 271-284, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31407590

RESUMO

Particulate matter 2.5 (PM2.5), aerodynamic diameter ≤ 2.5 µm, is the primary air pollutant that plays the key role for lung injury resulted from the loss of vascular barrier integrity. Cudratricusxanthone O (CTXO) is a novel xanthone compound isolated from the root of Cudrania tricuspidata Bureau. Here, we investigated the beneficial effects of CTXO against PM-induced lung endothelial cell (EC) barrier disruption and pulmonary inflammation. Permeability, leukocyte migration, activation of proinflammatory proteins, generation of reactive oxygen species (ROS), and histology were examined in PM2.5-treated ECs and mice. CTXO significantly scavenged PM2.5-induced ROS and inhibited the ROS-induced activation of p38 mitogen-activated protein kinase (MAPK). Concurrently, CTXO activated Akt, which helped maintain endothelial integrity. Furthermore, CTXO reduced vascular protein leakage, leukocyte infiltration, and proinflammatory cytokine release in the bronchoalveolar lavage fluid in PM-induced lung tissues. These results indicated that CTXO may exhibit protective effects against PM-induced inflammatory lung injury and vascular hyperpermeability.


Assuntos
Poluentes Atmosféricos/efeitos adversos , Lesão Pulmonar/prevenção & controle , Material Particulado/efeitos adversos , Pneumonia/prevenção & controle , Substâncias Protetoras/farmacologia , Xantonas/farmacologia , Animais , Células Endoteliais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Moraceae/química
19.
Pharm Biol ; 59(1): 1058-1064, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34365913

RESUMO

CONTEXT: Streblus asper Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation. OBJECTIVE: The study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of S. asper. MATERIALS AND METHODS: Antidiabetic effects were assessed by inducing diabetes in Wistar albino rats (n = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay. RESULTS: Methanol extracts of leaves and bark, and the aqueous extract of leaves of S. asper, caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC50 values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC50 values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively. DISCUSSION AND CONCLUSIONS: The methanol bark extract of S. asper showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Moraceae/química , Extratos Vegetais/farmacologia , Aloxano/farmacologia , Animais , Bangladesh , Glicemia , Diabetes Mellitus Experimental/induzido quimicamente , Glibureto/farmacologia , Modelos Animais , Casca de Planta/química , Extratos Vegetais/toxicidade , Ratos , Ratos Wistar
20.
Crit Rev Food Sci Nutr ; 60(3): 494-514, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-30582344

RESUMO

The tumor is becoming a critical threat to our lives in these years. Searching for antitumor substances from natural products is a great interest of scientists. Cudrania tricuspidata (C. tricuspidata) is a regional plant containing 158 flavonoids and 99 xanthones, and others ingredients with favorable bioactivity. This review comprehensively analyzes the antitumor compounds from C. tricuspidata against different tumors, and 78 flavonoids plus xanthones are considered as underlying antineoplastic. Importantly, the structure of preylation groups is the primary source of antitumor activity among 45 flavonoids plus xanthones, which could be a direction of structural modification for a better antitumor ability. Additionally, the fruits are also preferable sources of antitumor compounds compared to the roots and barks due to the abundant isoflavones and sustainability. However, many studies only focused on the cells viability inhibition of the compounds, the underlying molecular mechanisms, and the intracellular targets remain ambiguous. In conclusion, C. tricuspidata has a great potential for anti-tumor prevention or therapy, but more attention should be paid to deeper research in vitro and in vivo models.


Assuntos
Antineoplásicos/isolamento & purificação , Antineoplásicos/farmacologia , Flavonoides/farmacologia , Moraceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Xantonas/farmacologia , Antineoplásicos/química , Flavonoides/isolamento & purificação , Frutas/química , Humanos , Xantonas/isolamento & purificação
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