Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 6.602
Filtrar
1.
Food Chem ; 370: 131067, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34537430

RESUMO

This study evaluated different ultrasonic treatments for lignan biosynthesis in two varieties of flax sprouts. Results showed that lignans in flax sprouts significantly raised with ultrasonic pretreatment. Secoisolariciresinol diglucoside dramatically increased by about 6-fold at the flax sprouts. Ultrasonic pretreatment could also affect the accumulation of caffeic acid and p-coumaric acid in flax sprouts. Moreover, it is suggested that fiber flax sprout was more sensitive to ultrasonic pretreatment. The expression levels of genes involved in the biosynthesis of lignan were analyzed and the results could partly explain the accumulation of these compounds. The contents of secoisolariciresinol diglucoside were clustered with ferulic acid, which indicated that the accumulation of ferulic acid might be the key factor during flax sprout maturation for lignan accumulation. Present study could be useful guidance for ultrasonic pretreatment in the promotion of lignan accumulation and the fortification of nutritional values in flax sprouts as a functional vegetable.


Assuntos
Linho , Lignanas , Ultrassom
2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 37(5): 506-510, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34816662

RESUMO

Objective: To investigate the synergistic effects of magnolol and gefitinib on non-small cell lung cancer A549 cells. Methods: A549 cells were treated with Magnolol (6.25~500 µmol/L) or gefitinib (6.25~500 µmol/L) for 24 h, respectively, and the cell viability was detected by cell counting Kit-8 (CCK-8) experiment (n=3). Magnolol 100 µmol/L and gefitinib 5 µmol/L were selected in the following experiments (n=3, 24 h). Control group, magnolol group, gefitinib group and magnolol+gefitinib group were set up for factorial analysis. Colony formation experiment was applied to detect the cell proliferation. Western blot was used to detect protein expressions. Flow cytometry was applied to test cell apoptosis and sorting CD44+ and CD133+ cells. Results: Compared with the control group, the colony formation rate of Magnolol or Gefitinib groups was decreased significantly (P<0.05); the apoptosis rate was increased significantly (P<0.05); the number of CD44+ and CD133+ cells was reduced significantly (P<0.05); the expressions of Ki67, PCNA, and stem cell marker proteins SOX2 and OCT4 were down-regulated (P<0.05); and the ratio of Bax/Bcl-2 was increased significantly (P<0.05). Compared with the Magnolol group or Gefitinib group, the Magnolol+Gefitinib group further promoted the above changes (P<0.05), and the apoptosis rate, the ratio of Bax/Bcl-2, SOX2 and OCT4 all showed interactions between magnolol and gefitinib (P<0.05). Conclusion: Magnolol and gefitinib promote the apoptosis of A549 cells and inhibit its stem cell-like properties, and the effect of the two combined is better than separated administration. Magnolol and gefitinib have interactive effects on A549 cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células A549 , Apoptose , Compostos de Bifenilo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células , Gefitinibe/farmacologia , Humanos , Lignanas , Neoplasias Pulmonares/tratamento farmacológico
3.
Zhongguo Zhong Yao Za Zhi ; 46(20): 5270-5277, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738429

RESUMO

Dirigent(DIR) proteins are involved in the biosynthesis of lignin, lignans, and gossypol in plants and respond to biotic and abiotic stresses. Based on the full-length transcriptome of Schisandra chinensis, bioinformatics methods were used to preliminarily identify the DIR gene family and analyze the physico-chemical properties, subcellular localization, conserved motifs, phylogeny, and expression patterns of the proteins. The results showed that a total of 34 DIR genes were screened and the encoded proteins were 156-387 aa. The physico-chemical properties of the proteins were different and the secondary structure was mainly random coil. Half of the DIR proteins were located in chloroplast, while the others in extracellular region, endoplasmic reticulum, cytoplasm, etc. Phylogenetic analysis of DIR proteins from S. chinensis and the other 8 species such as Arabidopsis thaliana, Oryza sativa, and Glycine max demonstrated that all DIR proteins were clustered into 5 subfamilies and that DIR proteins from S. chinensis were in 4 subfamilies. DIR-a subfamily has the unique structure of 8 ß-sheets, as verified by multiple sequence alignment. Finally, through the analysis of the transcriptome of S. chinensis fruit at different development stages, the expression pattern of DIR was clarified. Combined with the accumulation of lignans in fruits at different stages, DIR might be related to the synthesis of lignans in S. chinensis. This study lays a theoretical basis for exploring the biological functions of DIR genes and elucidating the biosynthesis pathway of lignans in S. chinensis.


Assuntos
Lignanas , Schisandra , Frutas/química , Frutas/genética , Lignanas/análise , Filogenia , Alinhamento de Sequência
4.
PLoS One ; 16(10): e0258607, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34648570

RESUMO

Staphylococcus aureus and Methicillin-resistant S. aureus (MRSA) remains one of the major concerns of healthcare associated and community-onset infections worldwide. The number of cases of treatment failure for infections associated with resistant bacteria is on the rise, due to the decreasing efficacy of current antibiotics. Notably, Acrophialophora levis, a thermophilous fungus species, showed antibacterial activity, namely against S. aureus and clinical MRSA strains. The ethyl acetate extract of culture filtrate was found to display significant activity against S. aureus and MRSA with a minimum inhibitory concentration (MIC) of 1 µg/mL and 4 µg/mL, respectively. Scanning electron micrographs demonstrated drastic changes in the cellular architecture of metabolite treated cells of S. aureus and an MRSA clinical isolate. Cell wall disruption, membrane lysis and probable leakage of cytoplasmic are hallmarks of the antibacterial effect of fungal metabolites against MRSA. The ethyl acetate extract also showed strong antioxidant activity using two different complementary free radicals scavenging methods, DPPH and ABTS with efficiency of 55% and 47% at 1 mg/mL, respectively. The total phenolic and flavonoid content was found to be 50 mg/GAE and 20 mg/CAE, respectively. More than ten metabolites from different classes were identified: phenolic acids, phenylpropanoids, sesquiterpenes, tannins, lignans and flavonoids. In conclusion, the significant antibacterial activity renders this fungal strain as a bioresource for natural compounds an interesting alternative against resistant bacteria.


Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Fatores Biológicos/farmacologia , Staphylococcus aureus Resistente à Meticilina/ultraestrutura , Sordariales/química , Acetatos/química , Antibacterianos/química , Antioxidantes/química , Fatores Biológicos/química , Flavonoides/isolamento & purificação , Hidroxibenzoatos/isolamento & purificação , Índia , Lignanas/isolamento & purificação , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Sesquiterpenos/isolamento & purificação , Taninos/isolamento & purificação
5.
Molecules ; 26(20)2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34684767

RESUMO

Previously, the authors conducted phytochemical investigations of the aerial parts of Larrea tridentata and reported triterpene glycosides and lignan derivatives. In continuation of the preceding studies, 17 lignans and lignan glycosides (1-17) were isolated, including seven new compounds (1-7). Herein, the structure of the new compounds was determined based on spectroscopic analysis and enzymatic hydrolysis. The cytotoxicity of 1-17 against HL-60 human promyelocytic leukemia cells was examined. Compounds 4-11 and 14-16 were cytotoxic to HL-60 cells, with IC50 values in the range of 2.7-17 µM. Compound 6, which was the most cytotoxic among the unprecedented compounds, was shown to induce apoptotic cell death in HL-60 cells.


Assuntos
Antineoplásicos Fitogênicos/química , Glicosídeos/química , Larrea/química , Lignanas/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/farmacologia , Células HL-60 , Humanos , Lignanas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Componentes Aéreos da Planta/química , Triterpenos/química , Triterpenos/farmacologia
6.
Life Sci ; 285: 120013, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34614418

RESUMO

AIMS: Due to poor targeting ability of anti-tumor drugs and self-adaptation of tumors, the chemotherapy of ovarian cancer is still poorly effective. In recent years, the treatment of tumor with nano-targeted agents has become a potential research focus. In this study, a new type of short cell-penetrating peptide RPV-modified paclitaxel plus schisandrin B liposomes were constructed to disrupt VM channels, angiogenesis, proliferation and migration for the treatment of ovarian cancer. MATERIALS AND METHODS: In this study, clone assay, TUNEL, Transwell, wound-healing, CAM and mimics assay were used to detect the effects of RPV-modified liposomes on ovarian cancer SK-OV-3 cells before and after treatment. HE-staining, immunofluorescence and ELISA were used to further detect the expression of tumor-related proteins. KEY FINDINGS: RPV-modified paclitaxel plus schisandrin B liposomes can inhibit angiogenesis, VM channel formation, invasion and proliferation of ovarian SK-OV-3 cells. In vitro and in vivo studies showed that tumor-related protein expression was down-regulated. Modification of RPV can prolong the retention time of liposome in vivo and accumulate in the tumor site, increasing the anti-tumor efficacy. SIGNIFICANCE: The RPV-modified paclitaxel plus schisandrin B liposomes have good anti-tumor effect, thus may provide a new avenue for the treatment of ovarian cancer.


Assuntos
Antineoplásicos/administração & dosagem , Peptídeos Penetradores de Células , Lignanas/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/administração & dosagem , Compostos Policíclicos/administração & dosagem , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Ciclo-Octanos/administração & dosagem , Ciclo-Octanos/química , Feminino , Humanos , Lignanas/química , Lipossomos , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/química , Compostos Policíclicos/química , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Chin J Nat Med ; 19(9): 675-679, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34561078

RESUMO

Buxrugulosides A-E, four lignan glycosides (1-4) and a protocatechuate derivative (5) featuring a rare (N, N-diethyl)methyl amino group at aromatic rings, were obtained from the aerial parts of Buxus rugulosa, which is famous for treating coronary heart disease. Their structures including absolute configurations were elucidated by HRMS, 1D and 2D NMR, and by comparing their CD data with previous reports. Compound 1 was a rare sesquilignan, and all of these compounds were the first example of lignans with (N, N-diethyl)methyl amino group.


Assuntos
Buxus , Lignanas , Glicosídeos , Estrutura Molecular , Extratos Vegetais
8.
Chin J Nat Med ; 19(9): 700-705, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34561082

RESUMO

Biotransformation of α-asarone by Alternaria longipes CGMCC 3.2875 yielded two pairs of new neolignans, (+) (7S, 8S, 7'S, 8'R) iso-magnosalicin (1a)/(-) (7R, 8R, 7'R, 8'S) iso-magnosalicin (1b) and (+) (7R, 8R, 7'S, 8'R) magnosalicin (2a)/(-) (7S, 8S, 7'R, 8'S) magnosalicin (2b), and four known metabolites, (±) acoraminol A (3), (±) acoraminol B (4), asaraldehyde (5), and 2, 4, 5-trimethoxybenzoic acid (6). Their structures, including absolute configurations, were determined by extensive analysis of NMR spectra, X-ray crystallography, and quantum chemical ECD calculations. The cytotoxic activity and Aß42 aggregation inhibitory activity of all the compounds were evaluated. Compound 2 displayed significant anti-Aß42 aggregation activity with an inhibitory rate of 60.81% (the positive control EGCG: 69.17%). In addition, the biotransformation pathway of α-asarone by Alternaria longipes CGMCC 3.2875 was proposed.


Assuntos
Alternaria , Lignanas , Derivados de Alilbenzenos , Anisóis , Biotransformação , Estrutura Molecular
9.
Int J Mol Sci ; 22(18)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34576213

RESUMO

Diabetes mellitus is a chronic metabolic disease characterized by disturbances in carbohydrate, protein, and lipid metabolism, often accompanied by oxidative stress. Diabetes treatment is a complicated process in which, in addition to the standard pharmacological action, it is necessary to append a comprehensive approach. Introducing the aspect of non-pharmacological treatment of diabetes allows one to alleviate its many adverse complications. Therefore, it seems important to look for substances that, when included in the daily diet, can improve diabetic parameters. Magnolol, a polyphenolic compound found in magnolia bark, is known for its health-promoting activities and multidirectional beneficial effects on the body. Accordingly, the goal of this review is to systematize the available scientific literature on its beneficial effects on type 2 diabetes and its complications. Taking the above into consideration, the article collects data on the favorable effects of magnolol on parameters related to glycemia, lipid metabolism, or oxidative stress in the course of diabetes. After careful analysis of many scientific articles, it can be concluded that this lignan is a promising agent supporting the conventional therapies with antidiabetic drugs in order to manage diabetes and diabetes-related diseases.


Assuntos
Compostos de Bifenilo/farmacologia , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Lignanas/metabolismo , Animais , Glicemia/análise , Nefropatias Diabéticas/tratamento farmacológico , Oftalmopatias/tratamento farmacológico , Homeostase , Humanos , Hipoglicemiantes/farmacologia , Inflamação , Lignanas/farmacologia , Metabolismo dos Lipídeos , Magnolia , Camundongos , Estresse Oxidativo , Casca de Planta , Polifenóis/química , Resultado do Tratamento
10.
Int J Nanomedicine ; 16: 5693-5712, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34465990

RESUMO

Background: Honokiol (HK) is a natural bioactive compound with proven antineoplastic properties against melanoma. However, it shows very low bioavailability when administered orally. Alternatively, topical administration may offer a promising route. The objective of the current study was to fabricate HK transfersomes (HKTs) for topical treatment of melanoma. As an ultradeformable carrier system, transfersomes can overcome the physiological barriers to topical treatment of melanoma: the stratum corneum and the anomalous tumor microenvironment. Moreover, the immunomodulatory and stemness-regulation roles of HKTs were the main interest of this study. Methods: TFs were prepared using the modified scalable heating method. A three-factor, three-level Box-Behnken design was utilized for the optimization of the process and formulation variables. Intracellular uptake and cytotoxicity of HKTs were evaluated in nonactivated and stromal cell-activated B16F10 melanoma cells to investigate the influence of the complex tumor microenvironment on the efficacy of HK. Finally, ELISA and Western blot were performed to evaluate the expression levels of TGF-ß and clusters of differentiation (CD47 and CD133, respectively). Results: The optimized formula exhibited a mean size of 190 nm, highly negative surface charge, high entrapment efficiency, and sustained release profile. HKTs showed potential to alleviate the immunosuppressive characteristics of B16F10 melanoma in vitro via downregulation of TGF-ß signaling. In addition, HKTs reduced expression of the "do not eat me" signal - CD47. Moreover, HKTs possessed additional interesting potential to reduce the expression of the stem-like cell marker CD133. These outcomes were boosted upon combination with metformin, an antihyperglycemic drug recently reported to possess different functions in cancer, while combination with collagenase, an extracellular matrix-depleting enzyme, produced detrimental effects. Conclusion: HKTs represent a promising scalable formulation for treatment of the aggressive B16F10 melanoma, which is jam-packed with immunosuppressive and stem-like cell markers.


Assuntos
Antineoplásicos , Lignanas , Melanoma , Antineoplásicos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Humanos , Lignanas/farmacologia , Lignanas/uso terapêutico , Melanoma/tratamento farmacológico , Microambiente Tumoral
11.
Poult Sci ; 100(10): 101371, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34481217

RESUMO

This study evaluated the therapeutic efficacy of Schisandrin A on systemic colibacillosis of chickens. One hundred and eighty, 1-day-old Hailan Brown chickens were divided into 6 groups of 30 chickens each and assigned to the following treatments: 1) uninfected/untreated control; 2) infected Escherichia coli; 3) infected-plus low dose of Schisandrin A therapy (50 mg/kg); 4) infected-plus medium dose of Schisandrin A therapy (100 mg/kg); 5) infected-plus high dose of Schisandrin A therapy (200 mg/kg) and 6) infected-plus antimicrobial therapy (florfenicol). Each group of chickens was placed in cages with a photoperiod of 12 h of light and 12 h of dark. Feed and water for all groups were provided ad libitum for the duration of the study. On d 14, all the chickens except the uninfected control group were intraperitoneally inoculated with a fresh culture of E. coli containing 1 × 108 CFU/mL. The parameters measured included: average daily weight gain (ADG), percent survivability, liver index, serum activity of enzymes (ALT and AST), hepatic and intestinal concentrations of TNF-α, IL-1ß, IL-6, IL-8, and LPS, expression of tight junction proteins (occludin, ZO-1, and claudin-1), relative abundance of bacterial species and histopathological changes in hepatic and intestinal tissue. The results showed that the medium and high doses of Schisandrin A ameliorated the detrimental effects of colibacillosis on weight gain. Regarding organ indexes, E. coli infection induced a significant increase in liver index, all the doses of Schisandrin A produced a significant reduction of liver index in comparison to the E. coli infected control. Serum activity of ALT and AST enzymes significantly increased due to E. coli infection, with the exception of the low dose of Schisandrin A for AST enzyme activity, all the Schisandrin A treatments significantly lowered enzyme activity in comparison to the E. coli infected control. Regarding concentrations of inflammatory markers in hepatic and intestinal, E. coli infection caused a significant increase in TNF-α, IL-1ß, IL-6, and IL-8, except the lowest dose of Schisandrin A for IL-1ß, the rest of the doses tested were able to significantly reduced the concentrations of inflammatory markers. Concentrations of LPS in hepatic and intestinal tissues were significantly increased by E. coli infection, all doses of Schisandrin A significantly reduced the concentration of LPS in hepatic and intestinal tissue. E. coli infection significantly reduced the expression of 2 tight junction proteins (ZO-1 and Claudin-1), the higher doses of Schisandrin A were effective in significantly increasing the expression of these tight junction proteins when compared with the E. coli infected control. Taken together, these results show that Schisandrin A has potential as an alternative therapy for the treatment of colibacillosis in chickens.


Assuntos
Galinhas , Infecções por Escherichia coli , Animais , Ciclo-Octanos , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/veterinária , Lignanas , Fígado , Compostos Policíclicos
12.
Nanoscale ; 13(32): 13681-13692, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34477643

RESUMO

A hypoxic environment in tumors hampers the therapeutic efficacy of radiotherapy. Moreover, radiotherapy, a localized treatment technique, can barely control tumor metastases. Herein, poly(lactic-co-glycolic acid) was used to encapsulate perfluorocarbon (PFC) for increasing the oxygen level and a lignan-derived compound (Q1) for enhancing IL-25 secretion from fibroblasts, thereby boosting the radiotherapeutic effect on local and distant tumors. The prepared co-delivery nanoplatform, PFC-Q1@PLGA, has a nano-scale size of around 160 nm and a negative zeta potential (about -13 mV). PFC-Q1@PLGA treatment leads to an arrest of the G2 phase (4n) in the cell cycle and reduces the mitochondria membrane potential. A high expression level of IL-25 in fibroblasts is detected after the cells are treated with PFC-Q1@PLGA, which increases the late apoptosis percentage of 4T1 cells after treatment with IL-25-containing conditional medium from fibroblasts. The oxygen level in tumors is significantly promoted to about 52.3% after injection of oxygen-saturated PFC-Q1@PLGA (O2), which is confirmed from the functional magnetic resonance images of the tumor site in mice. The in vivo study demonstrates that the injection of PFC-Q1@PLGA (O2) into local tumors significantly enhances the radiotherapeutic effect on local tumors and also inhibits the growth of remote tumors by an enhanced abscopal effect. This study presents a novel radiotherapy strategy to enable synergistic whole-body therapeutic responses after localized treatment with PFC-Q1@PLGA (O2).


Assuntos
Fluorcarbonetos , Lignanas , Nanopartículas , Neoplasias , Animais , Camundongos , Oxigênio , Microambiente Tumoral
13.
J Agric Food Chem ; 69(40): 11781-11793, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34582205

RESUMO

Plant pathogenic fungi seriously affect agricultural production and are difficult to control. The discovery of new leads based on natural products is an important way to innovate fungicides. In this study, 30 natural-product-based magnolol derivatives were synthesized and characterized on the basis of NMR and mass spectroscopy. Bioactivity tests on phytopathogenic fungi (Rhizoctonia solani, Fusarium graminearum, Botrytis cinerea, and Sclerotinia sclerotiorum) in vitro of these compounds were performed systematically. The results showed that 11 compounds were active against four kinds of phytopathogenic fungi with EC50 values in the range of 1.40-20.00 µg/mL, especially compound L5 that exhibited excellent antifungal properties against B. cinerea with an EC50 value of 2.86 µg/mL, approximately 2.8-fold more potent than magnolol (EC50 = 8.13 µg/mL). Moreover, compound L6 showed the highest antifungal activity against F. graminearum and Rhophitulus solani with EC50 values of 4.39 and 1.40 µg/mL, respectively, and compound L7 showed good antifungal activity against S. sclerotiorum. Then, an in vivo experiment of compound L5 against B. cinerea was further investigated in vivo using infected tomatoes (curative effect, 50/200 and 36%/100 µg/mL). The physiological and biochemical studies illustrated that the primary action mechanism of compound L5 on B. cinerea might change the mycelium morphology, increase cell membrane permeability, and destroy the function of mitochondria. Furthermore, structure-activity relationship (SAR) studies revealed that hydroxyl groups play a key role in antifungal activity. To sum up, this study provides a reference for understanding the application of magnolol-based antifungal agents in crop protection.


Assuntos
Antifúngicos , Fungicidas Industriais , Animais , Antifúngicos/farmacologia , Ascomicetos , Compostos de Bifenilo , Botrytis , Fungicidas Industriais/farmacologia , Fusarium , Lignanas , Estrutura Molecular , Rhizoctonia , Relação Estrutura-Atividade
14.
J Biomed Nanotechnol ; 17(8): 1564-1573, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544534

RESUMO

Honokiol-loaded nanoparticles (HK-loaded NPs) exhibit potential antitumor activity; however, the factors affecting their antitumor efficacy are still unclear and need to be explored. This research was aimed to systematically estimate the influence of feed weight ratio (FWR) and nanocarrier structure on antitumor activity. Accordingly, three types of ethylene glycol derivatives, including linear poly(ethylene glycol) with molar mass of 2000 (PEG45), first and second generation oligo(ethylene glycol) dendrons (G1 and G2) were used as nanocarriers, and a series of HK-loaded NPs with different FWR were prepared successfully using the evaporation-ultrasonication method. These NPs showed similar stability but demonstrated differences with respect to particle size, morphology, cumulative profile, and antitumor efficacy. The influence of the FWR was studied using G1 dendrons as nanocarriers; the results indicated that the particle size and morphology of G1 NPs were significantly affected, and G1 NPs (8/1), with the FWR of 8/1 for HK versus G1 dendron, exhibited the highest antitumor activity among all G1 NPs. Furthermore, the influence of nanocarrier structure was investigated at the FWR of 4/1; the findings revealed reduction in the particle diameter from 280 nm to 109 nm and change in morphology from sphere to flower-like structure with an increase in the branch degree from linear to dendron. Moreover, G2 NPs (4/1), with the FWR of 4/1 for HK versus G2 dendron, carrying the highest branch degree exhibited the greatest antitumor efficacy among all. These results are suggestive of influence of particle size and morphology on antitumor efficacy of HK-loaded NPs. Conclusively, this study demonstrated nanocarrier structure and the FWR significantly affect the antitumor efficacy of NPs, which should be optimized for designing nanoscale delivery systems.


Assuntos
Portadores de Fármacos , Nanopartículas , Compostos de Bifenilo , Linhagem Celular Tumoral , Etilenoglicóis , Lignanas , Nanomedicina , Tamanho da Partícula , Poliésteres , Polietilenoglicóis
15.
Molecules ; 26(17)2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34500615

RESUMO

Juniper representatives are natural sources of plenty of bioactive metabolites and have been used since ancient times as folk remedies against tapeworms, warts, cancer, etc. The antiproliferative activities of junipers are attributed to podophyllotoxin (PPT), which is a precursor for the synthesis of efficient anticancer drugs. However, the natural sources of PPT, Sinopodophyllum hexandrum (Royle) T. S. Ying and Podophyllum peltatum L., are already endangered species because of their intensive industrial exploitation. Therefore, identification of other sources of PPT is necessary. This study is a broad comparative investigation of junipers, for which original sources have been accessed from different continents of the world. The present research is aimed at the identification of species, producing PPT and other lignans at concentrations that are sufficient for the high antiproliferative activity of the corresponding extracts. Cytotoxic juniper leaf extracts demonstrated a broad spectrum of activity on a panel of cancer cell lines. The antiproliferative properties of junipers were attributed to the combined activity of great diversity of lignans (podophyllotoxin, deoxypodophyllotoxin, ß-peltatin, yatein, matairesinol, anhydropodorhizol, etc.), detected by UHPLC-HRMS and LC-ESI-MS/MS in the corresponding extracts. Several species of the genus Juniperus L. were outlined as perspective sources of drug precursors with potential pharmaceutical applications.


Assuntos
Antineoplásicos/farmacologia , Juniperus/química , Podofilotoxina/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células HT29 , Humanos , Células K562 , Lignanas/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Pró-Fármacos/farmacologia
16.
Molecules ; 26(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34577136

RESUMO

Extensive epigenetic remodeling occurs during the cell fate determination of stem cells. Previously, we discovered that eudesmin regulates lineage commitment of mesenchymal stem cells through the inhibition of signaling molecules. However, the epigenetic modulations upon eudesmin treatment in genomewide level have not been analyzed. Here, we present a transcriptome profiling data showing the enrichment in PRC2 target genes by eudesmin treatment. Furthermore, gene ontology analysis showed that PRC2 target genes downregulated by eudesmin are closely related to Wnt signaling and pluripotency. We selected DKK1 as an eudesmin-dependent potential top hub gene in the Wnt signaling and pluripotency. Through the ChIP-qPCR and RT-qPCR, we found that eudesmin treatment increased the occupancy of PRC2 components, EZH2 and SUZ12, and H3K27me3 level on the promoter region of DKK1, downregulating its transcription level. According to the analysis of GEO profiles, DEGs by depletion of Oct4 showed an opposite pattern to DEGs by eudesmin treatment. Indeed, the expression of pluripotency markers, Oct4, Sox2, and Nanog, was upregulated upon eudesmin treatment. This finding demonstrates that pharmacological modulation of PRC2 dynamics by eudesmin might control Wnt signaling and maintain pluripotency of stem cells.


Assuntos
Furanos , Lignanas , Transcriptoma , Diferenciação Celular , Linhagem Celular , Reposicionamento de Medicamentos , Histonas/metabolismo , Fator 3 de Transcrição de Octâmero , Complexo Repressor Polycomb 2 , Via de Sinalização Wnt
17.
Phytochemistry ; 192: 112958, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34560578

RESUMO

Wild chervil (Anthriscus sylvestris) is a widespread, wild-growing herbaceous plant from Apiaceae family, known for high content of lignans related to podophyllotoxin, and thus representing a promising new source for their industrial isolation. The data on detailed chemical profile of A. sylvestris lignans are still lacking. By combining fractionation with non-targeted LC-DAD-ESI-MS/MS metabolite profiling, we have identified, fully or tentatively, 46 lignans, 12 of which were never reported in A. sylvestris and 19 in any biological source. The dominant lignans were found to be nemerosin, yatein, deoxypodophyllotoxin, podophyllotoxin, podophyllotoxone and guayadequiol. In addition to well-known dibenzylbutyrolactones, aryltetralins and 7-oxygenated aryltetralins, we found several oxygenated lignan classes previously undescribed in A. sylvestris - 7-hydroxy, 7-oxo and 8-hydroxydibenzylbutyrolactones, a 7'-oxotetrahydrofuran and a 7-hydroxyarylnaphthalene. To facilitate future rapid classification and identification of lignans in raw extracts, UV, MS and NMR spectral features of different lignan classes are described.


Assuntos
Apiaceae , Lignanas , Extratos Vegetais , Podofilotoxina , Espectrometria de Massas em Tandem
18.
Front Cell Infect Microbiol ; 11: 730222, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34540720

RESUMO

Toxoplasma gondii (T. gondii) is an important health problem in human and animals, and the highlighting side effects of launched therapeutic chemicals cannot be ignored. Thus, it is urgent to develop new drugs to against the infection. Myrislignan originated from nutmeg exhibited excellent anti-T. gondii activity in vitro and in vivo, and was able to destroy mitochondrial function. However, the exact mechanism of action is still unknown. In this study, combining RNAs deep-sequencing analysis and surface plasmon resonance (SPR) analysis, the differentially expressed genes (DEGs) and high affinity proteins suggested that myrislignan may affect the oxidation-reduction process of T. gondii. Furthermore, the upregulating ROS activity after myrislignan incubation verified that myrislignan destroyed the oxidant-antioxidant homeostasis of tachyzoites. Transmission electron microscopy (TEM) indicated that myrislignan induced the formation of autophagosome-like double-membrane structure. Moreover, monodansyl cadaverine (MDC) staining and western blot further illustrated autophagosome formation. Myrislignan treatment induced a significant reduction in T. gondii by flow cytometry analysis. Together, these findings demonstrated that myrislignan can induce the oxidation-reduction in T. gondii, lead to the autophagy, and cause the death of T. gondii.


Assuntos
Lignanas , Toxoplasma , Animais , Autofagia , Humanos , Oxirredução
19.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3846-3852, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472258

RESUMO

The lignans in Urtica cannabina were isolated by preparative HPLC, silica, and ODS column chromatographies, and identified by NMR and HR-MS. The inhibitory activities on 5α-reductase were evaluated in vitro. As a result, ten secolignans,(2R,4S)-2,4-bis(3-methoxyl-4-hydroxyphenyl)-3-butoxypropanol(1), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone(2), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(3), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl] butyrolactone(trans urticol, 4), 3,4-trans-3-hydroxymethyl-4-[bis(3,4-dimethoxyphenyl)methyl] butyrolactone-3-O-ß-D-glucopyranoside(5), 3,4-trans-3-hydroxymethyl-4-[(3,4-dimethoxyphenyl)(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-ß-D-glucopyranoside(6), 3,4-trans-3-hydroxymethyl-4-[bis(3-methoxyl-4-hydroxyphenyl)methyl]butyrolactone-3-O-ß-D-glucopyranoside(trans-urticol-7-O-ß-D-glucopyranoside, 7), cycloolivil-4-O-ß-D-glucopyranoside(8), isolariciresinol-4'-O-ß-D-glucopyranoside(9), and olivil-4'-O-ß-D-glucopyranoside(10), together with a polyphenol [α-viniferin(11)], were isolated from U. cannabina for the first time. Compound 1 was a new lignan. Compound 7 was potent in inhibiting 5α-reductase.


Assuntos
Colestenona 5 alfa-Redutase/farmacologia , Lignanas , Urticaceae , Inibidores de 5-alfa Redutase , Cromatografia Líquida de Alta Pressão , Lignanas/farmacologia , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Urticaceae/efeitos dos fármacos , Urticaceae/enzimologia
20.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500623

RESUMO

Lignans are the main secondary metabolites synthetized by Linum species as plant defense molecules. They are also valuable for human health, in particular, for their potent antiviral and antineoplastic properties. In this study, the adventitious root cultures of three Linum species (L. flavum, L. mucronatum and L. dolomiticum) were developed to produce aryltetralin lignans. The effect of two elicitors, methyl jasmonate and coronatine, on aryltetralin lignans production was also evaluated. The adventitious root cultures from L. dolomiticum were obtained and analyzed for the first time and resulted as the best producer for all the aryltetralins highlighted in this system: Podophyllotoxin, 6-methoxypodophyllotoxin and 6-methoxypodophyllotoxin-7-O-ß-glucoside, the last showing a productivity of 92.6 mg/g DW. The two elicitors differently affected the production of the 6-methoxypodophyllotoxin and 6-methoxypodophyllotoxin-7-O-ß-glucoside.


Assuntos
Linho/metabolismo , Lignanas/biossíntese , Raízes de Plantas/metabolismo , Acetatos/metabolismo , Aminoácidos/biossíntese , Ciclopentanos/metabolismo , Indenos , Oxilipinas/metabolismo , Podofilotoxina/análogos & derivados , Podofilotoxina/biossíntese
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...