Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
1.
Phytochemistry ; 206: 113520, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36544302

RESUMO

Forest operations and wood industry generate large amounts of residues that are discarded in the field and cause environmental pollution. However, these biomass residues are still raw materials to obtain value-added products, such as essential oils, organic/aqueous extracts and resins that are among the great natural sources of bioactive metabolites. Thus, in recent years, the scientific community is giving special attention to their valorization. To date, different uses of biomass residues have been proposed, such as a source of renewable energy, fertilizers, animal feed and bioactive molecules. In this context, Cryptomeria japonica biomass residues (e.g., bark and its exudate, heartwood, sapwood, leaves, cones and roots) represent a source of diverse specialized metabolites (e.g., sesqui-, di-, tri- and sesquarterpenes, flavonoids, lignans and norlignans) with potential application in different fields, particularly in the agrochemical, food, cosmeceutical, pharmaceutical, phytomedicine and esthetic, due to their valuable multi-bioactivities determined over the last decades. Thus, this review provides an overview of the reported biological activities of organic extracts/fractions and their specialized metabolites obtained from different parts of C. japonica, in order to encourage the alternative uses of C. japonica wastes/byproducts, and implement a sustainable and circular bioeconomy.


Assuntos
Cryptomeria , Cupressaceae , Lignanas , Óleos Voláteis , Animais , Cupressaceae/química , Cryptomeria/química , Cryptomeria/metabolismo , Lignanas/metabolismo , Óleos Voláteis/química , Madeira/metabolismo
2.
Chem Pharm Bull (Tokyo) ; 70(10): 720-725, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36184455

RESUMO

Five podophyllotoxin derivatives (1-5), two diterpenoids (6 and 7), three diterpenoid xylosides (8-10), a flavanonol glycoside (11), flavonol (12), and biflavonoid (13) were isolated from the leaves of Thujopsis dolabrata (Cupressaceae). Compounds 1, 6, and 8 were named (-)-ß-isopeltatin, epi-nootkastatin 2, and acetoxyanticopalol 15-O-ß-D-xylopyranoside, respectively. The structures of the isolated compounds were determined based on a detailed analysis of NMR spectroscopic data and through chromatographic and spectroscopic analyses following specific chemical transformations. The isolated compounds (1-5 and 7-11) were evaluated for their cytotoxicity toward HL-60 human promyelocytic leukemia cells and Caki-1 human kidney carcinoma cells. The podophyllotoxin derivatives (1-5) exhibited cytotoxicity against both HL-60 and Caki-1 cells with IC50 values ranging from 0.00069 to 5.4 µM, and the diterpenoid derivatives (7-10) demonstrated cytotoxicity against HL-60 cells with IC50 values ranging from 4.5 to 11 µM. HL-60 cells treated with 8 exhibited apoptosis characteristics, such as accumulation of sub-G1 cells and nuclear chromatin condensation.


Assuntos
Antineoplásicos Fitogênicos , Biflavonoides , Cupressaceae , Diterpenos , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Cromatina , Cupressaceae/química , Diterpenos/farmacologia , Flavonóis , Glicosídeos/análise , Células HL-60 , Humanos , Folhas de Planta/química , Podofilotoxina/análise
3.
Molecules ; 26(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669825

RESUMO

The aim of the present research was to determine the chemical composition and the cytotoxic effects of Tetraclinis articulata trunk bark essential oil (HEE) obtained by steam distillation and five fractions obtained by normal phase silica chromatographic separation. Chemical analysis allowed the identification of 54 known compounds. Relatively high amounts of oxygenated sesquiterpenes (44.4-70.2%) were detected, mainly consisting of caryophyllene oxide (13.1-26.6%), carotol (9.2-21.2%),14-hydroxy-9-epi-(E)-caryophyllene (3.2-15.5%) and humulene epoxide II (2.6-7.2%). The cytotoxic activity against human mammary carcinoma cell lines (MDA-MB-231) and colorectal carcinoma cell lines (SW620) of the essential oil and its fractions were assessed. All the samples displayed moderate to weak activity compared to 5-fluorouracil. The colorectal carcinoma cell line was relatively more sensitive to the essential oil and its fractions compared to the breast cancer cell line, showing IC50 values from 25.7 to 96.5 µg/mL. In addition, the essential oil and its fraction E.2 revealed a cytotoxic activity against colorectal carcinoma cell line, with IC50 values lower than 30 µg/mL. This is the first report on the chemical composition and cytotoxic activity of the trunk bark essential oil of T. articulata.


Assuntos
Cupressaceae/química , Cupressaceae/crescimento & desenvolvimento , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Casca de Planta/química , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Fracionamento Químico , Humanos , Concentração Inibidora 50 , Tunísia
4.
Molecules ; 25(4)2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32093424

RESUMO

Taiwania flousiana (T. flousiana) Gaussen is a precious wood in the family Taxodiaceae. This study investigated the chemical components of the essential oil from the stem bark of T. flousiana and its algicidal, antifungal, and antioxidant properties. Sixty-nine compounds representing 89.70% of the stem bark essential oil were identified by GC-MS. The essential oil showed strong anti-algae, anti-bacteria, and anti-fungus activities against the tested species, and antioxidant activities. The IC50 values of the essential oil against chlorophyll a, chlorophyll b, and the total chlorophyll of Spirogyra communis (a species of algae), 24-96 h after the treatment, ranged from 31.77 to 84.92 µg/mL, while the IC50 values of butachlor ranged from 40.24 to 58.09 µg/mL. Ultrastructure changes revealed by the transmission electron microscopy indicated that the main algicidal action sites were the chloroplast and cell wall. The essential oil showed antifungal activities on Rhizoctonia solani (EC50 = 287.94 µg/mL) and Colletotrichum gloeosporioiles (EC50 = 378.90 µg/mL). It also showed bactericidal activities on Ralstonia solanacearum and Staphylococcus aureus, with zones of inhibition (ZOIs) being 18.66 and 16.75 mm, respectively at 40 µg/disk. Additionally, the essential oil possessed antioxidant activity estimated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) method (IC50 = 33.51 µg/mL; IC50 value of the positive control ascorbic acid was 7.98 µg/mL). Thus, the essential oil of this plant might be used as a possible source of natural bioactive molecules in agrochemical industry as well as in food and cosmetic industries.


Assuntos
Antioxidantes , Cupressaceae/química , Óleos Voláteis , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Colletotrichum/crescimento & desenvolvimento , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Ralstonia solanacearum/crescimento & desenvolvimento , Rhizoctonia/crescimento & desenvolvimento , Spirogyra/crescimento & desenvolvimento , Staphylococcus aureus/crescimento & desenvolvimento
5.
Nat Prod Res ; 34(12): 1763-1771, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30600693

RESUMO

Investigation of Platycladus orientalis yielded five flavonoids, including aglycone flavone 1 (apigenin), flavone glycoside 2 (apigenin 7-O-ß-D-glucopyranoside), new gernaylated flavone glycoside 3 (apigenin 8-gernayl-4'-O-α-gluco pyranoside) and two new pernylated flavonoid glycosides 4 & 5 (apigenin 8-pernyl-4'-glucopyranosyl-7-O-α-glucopyranoside and apigenin 5-pernyl-7-glucopyranosyl-4'-O-ß-D-glucopyranoside). Their structures were elucidated on the basis of spectroscopic evidence. The cytotoxicity of compounds 1-5 were tested against Lung adenocarcinoma (A549), human hepatocellular liver carcinoma (HepG2), human breast carcinoma (MCF-7) cell lines and mouse fibroblast cell line NIH/3T3 as normal cells. This assay gave spot on structure activity relationship which, showed that cytotoxicity of compounds (1) and (2) against three cell lines was weak as IC50 > 15. Compounds (4) and (5) had moderate cytotoxic and no toxic effect on normal cell. Compound (3) showed high cytotoxic activity against tested three cell lines with no toxic effect of normal cells.[Formula: see text].


Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Cupressaceae/química , Flavonoides/isolamento & purificação , Glicosídeos/isolamento & purificação , Componentes Aéreos da Planta/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular , Linhagem Celular Tumoral , Flavonoides/química , Flavonoides/toxicidade , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Relação Estrutura-Atividade
6.
J Cosmet Dermatol ; 19(5): 1254-1259, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31486569

RESUMO

BACKGROUND: Fitzroya cupressoides, commonly known as alerce, is an endemic conifer unique to southern South America. Alerce wood is renowned for its durability and resistance to biological degradation due to the presence of a particular class of secondary metabolite. Alerce extracts have been used in traditional medicine for different skin lesion treatments. AIMS: To develop a cell culture system to produce alerce extract and evaluate its cytotoxicity and effects on in vitro wound healing. METHODS: Cell cultures and aqueous extracts were prepared from alerce needles. Cytotoxicity was evaluated in keratinocytes (HaCaT line) and melanocites (C32 line) using the XTT assay. Wound healing was assayed with the scratch test in HaCaT cells, using mitomycin C to evaluate the role of cell division in the wound closure. RESULTS: Alerce cell culture extract has a significant effect on wound healing at different concentrations. No positive effects on the viability of normal and cancerous skin cells were observed. These results suggest that alerce extracts stimulate cell division in human skin epidermal cells in the context of wound repair. CONCLUSIONS: Bioactive compounds extracted from alerce cell cultures show promise as ingredients in dermocosmetic formulations, but further clinical studies are required to support these findings at the tissue level.


Assuntos
Extratos Celulares/farmacologia , Cosmecêuticos/farmacologia , Cupressaceae/química , Extratos Vegetais/farmacologia , Cicatrização/efeitos dos fármacos , Técnicas de Cultura de Células , Extratos Celulares/isolamento & purificação , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cosmecêuticos/isolamento & purificação , Cupressaceae/citologia , Humanos , Queratinócitos , Melanocortinas , Extratos Vegetais/isolamento & purificação , Testes de Toxicidade Aguda
7.
J Nat Prod ; 82(8): 2087-2093, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31347365

RESUMO

Two uncommon C37 heterodimeric diterpenoids, taicrypnacids A (1) and B (2), and a known labdane-type diterpenoid (3) were isolated from the leaves of Taiwania cryptomerioides. Several techniques, such as comprehensive spectroscopic analysis, chemical conversion, X-ray crystallography, and ECD data, were employed to define the structures. The two new compounds displayed cytotoxicity against human breast cancer (MCF-7), osteosarcoma (U-2 OS), and human colon carcinoma (HCT-116) cell lines, while the methyl ester 1a showed no activity. Compound 1 induced Ca2+-ROS pathway-mediated endoplasmic reticulum stress, and excessive stress led to cell death by activating apoptosis and autophagy.


Assuntos
Cupressaceae/química , Diterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Dimerização , Diterpenos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Células MCF-7 , Estrutura Molecular , Análise Espectral/métodos , Estereoisomerismo
8.
Carbohydr Polym ; 213: 276-285, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30879670

RESUMO

The structure and bioactivity of a novel polysaccharide from Platycladus orientalis (L.) Franco leaves (POP2) were investigated in the present study. Structure characterization demonstrated that the average molecular weight of POP2 was 9.69 kDa and consisted of arabinose (14.39%), mannose (10.24%), glucose (63.95%) and galactose (11.42%). The main linkage types of POP2 consisted of (1→4)-linked α-d-Glc and (1→6)-linked α-d-Glc based on methylation and NMR analysis. Bioactivity evaluation showed that POP2 could effectively promote the secretion of inflammatory cytokines (IL-6 and TNF-α), as well as the anti-inflammatory cytokines (IL-10) in LPS-induced cells. Besides, the secretion of NO was significantly inhibited by POP2 in M1 model. POP2 could enhance the level of inflammatory cytokines (NO, IL-6 and TNF-α), while the secretion of the anti-inflammatory cytokine TGF-ß was markedly suppressed in IL-4 induced cells. Our work attempted to elucidate the regulation of macrophage polarization and support the potential application of POP2 as bioactive ingredient for functional foods.


Assuntos
Cupressaceae/química , Macrófagos/efeitos dos fármacos , Polissacarídeos/farmacologia , Animais , Polaridade Celular/efeitos dos fármacos , Células Cultivadas , Macrófagos/metabolismo , Camundongos , Folhas de Planta/química , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Células RAW 264.7
9.
Phytochemistry ; 161: 86-96, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822624

RESUMO

A phytochemical study on the stem bark of Metasequoia glyptostroboides led to the isolation of sixty-one diterpenoids and sesquiterpenoids, including seventeen previously undescribed compounds, metaglyptins A-Q. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, and 1H, 13C and 2D NMR). The absolute configurations of metaglyptins I, J, and O were determined by the ECD data and single-crystal X-ray diffraction analysis. The undescribed compounds were evaluated for their cytotoxicity against HeLa, AGS, and MDA-MB-231 cancer cell lines. The results revealed that metaglyptin A exhibited moderate cytotoxicity against MDA-MB-231 cell line with IC50 value of 20.02 µM.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Cupressaceae/química , Diterpenos/farmacologia , Casca de Planta/química , Caules de Planta/química , Sesquiterpenos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Diterpenos/química , Diterpenos/isolamento & purificação , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Modelos Moleculares , Conformação Molecular , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade
10.
J Food Sci ; 84(3): 667-677, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30779137

RESUMO

The polyphenols (PF) from Platycladus Orientalis (L.) Franco leaves were purified by using 10 different macroporous adsorption resins. HPD-722 resin showed the best adsorption and desorption capacities. The static and dynamic adsorption and desorption of PF on HPD-722 resin were studied and the total polyphenols were separated into two fractions, PF-A and PF-B. PF-A and PF-B demonstrated similar scavenging activity of free radical (DPPH, ABTS, hydroxyl radical, superoxide anion). The scavenging activity of PF-A and PF-B on hydroxyl radical and superoxide anion radical reached the equal levels of vitamin C and gallic acid. The IC50 value of PF-A for hydroxyl radical scavenging activity and superoxide anion radical scavenging activity were 0.50 and 0.56 mg/mL, while those of PF-B were 0.61 and 0.64 mg/mL. PF-A and PF-B could reduce the overproduction of inflammatory cytokines (TNF-α, Pro-IL-1ß, and IL-6) induced by lipopolysaccharide and their protein expression in THP-1 cells. PF-B exhibited better anti-inflammatory effect than PF-A in the dosage range of 1.0-4.0 µg/mL. Structural identification of PF-A and PF-B were conducted by HPLC-MS/MS. Ten polyphenol compounds were identified in PF-A and PF-B, respectively, by HPLC-MS/MS, including quercetin, apigenin, myricetin, and so on. Molecular docking studies indicated that apigenin, myricetin, luteolin, kaempferol, and quercetin effectively inhibit xanthine oxidase by forming hydrogen bonds with the amino acid residues and binding to the active site of the enzyme. The results might supply useful information for better understanding the chemical structure, antioxidant, and anti-inflammatory activities of Platycladuso (L.) Franco leaves polyphenols. PRACTICAL APPLICATION: This study demonstrated that polyphenols from P. orientalis (L.) Franco leaves have the potential applications as functional food ingredient for the prevention and treatment of gout and inflammation, hyperuricemia and gout.


Assuntos
Cupressaceae/química , Polifenóis/química , Antioxidantes , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Citocinas/genética , Citocinas/metabolismo , Sequestradores de Radicais Livres , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Simulação de Acoplamento Molecular , Extratos Vegetais , Folhas de Planta/química , Superóxidos , Espectrometria de Massas em Tandem
11.
Phytomedicine ; 56: 57-63, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30668354

RESUMO

BACKGROUND: Tetraclinis articulata is used in traditional medicine and has been reported to possess antibacterial, antifungal, cytotoxic, anti-inflammatory and antioxidant properties. PURPOSE: This study investigated the effects of T. articulata essential oil on memory and brain oxidative stress in amyloid-ß peptide 1-42 (Aß1-42)-induced an Alzheimer's disease amyloidosis model. Moreover, the underlying mechanism for memory enhancement and antioxidant activity was investigated, thus supporting its traditional use with scientific evidence for further studies. METHODS: T. articulata essential oil was administered by inhalation to male Wistar rats once daily for 15 min period at doses of 1% and 3% for 21 days after the intracerebroventricular administration of Aß1-42 right-unilaterally to induce memory deficits. The chemical composition of the essential oil was done by GC-MS and GC-FID. Spatial memory of rats was tested using Y-maze and radial arm maze tests. The possible underlying mechanism for memory improvement exhibited by T. articulata essential oil was investigated by in vivo brain antioxidant effect and acetylcholinesterase (AChE) inhibitory effect. In vitro, experimental evaluations were assessed through DPPH and ABTS tests. RESULTS: The GC-MS and GC-FID data showed that the essential oil has a high percent of monoterpene hydrocarbons. Also, we demonstrated the essential oil reversed the Aß1-42-induced decreasing of the spontaneous alternation in the Y-maze test and the Aß1-42-induced increasing of the working and reference memory errors in the radial arm maze test. Furthermore, the Aß1-42-decreased the acetylcholinesterase activity and the oxidant-antioxidant status in the rat hippocampus was retrieved by the treatment with the essential oil. CONCLUSION: The study demonstrates that the essential oil could be a potent pharmacological agent against dementia by modulating cholinergic activity and promoting antioxidant action in the rat hippocampus.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Transtornos Cognitivos/tratamento farmacológico , Cupressaceae/química , Óleos Voláteis/farmacologia , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/toxicidade , Amiloidose/induzido quimicamente , Animais , Antioxidantes/farmacologia , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Inibidores da Colinesterase/farmacologia , Transtornos Cognitivos/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Masculino , Transtornos da Memória/tratamento farmacológico , Óleos Voláteis/química , Estresse Oxidativo/efeitos dos fármacos , Fragmentos de Peptídeos/toxicidade , Ratos Wistar , Memória Espacial/efeitos dos fármacos
12.
Org Biomol Chem ; 16(46): 9059-9063, 2018 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-30444234

RESUMO

Biogenesis-inspired chemical research of the leaves of Taiwania cryptomerioides afforded four unprecedented dimeric diterpenes, featuring a tetracyclic [7. 75, 9. 4. 05, 10. 08, 9] octodecane core: taiwanoids A-D (1-4). The structures of these compounds were determined on the basis of comprehensive spectral analysis, chemical conversions and X-ray crystallography. A possible biosynthetic pathway for compounds 1-4 was proposed. Compounds 2 and 3 exerted a 5.37 and 6.26-fold potentiation effect on bortezmib (BTZ) susceptibility at a tested concentration of 20 µM, respectively.


Assuntos
Abietanos/química , Cupressaceae/química , Abietanos/farmacologia , Antineoplásicos/farmacologia , Bortezomib/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X , Dimerização , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Modelos Moleculares , Neoplasias/tratamento farmacológico , Extratos Vegetais/química , Extratos Vegetais/farmacologia
13.
Chem Biodivers ; 15(8): e1800148, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29790302

RESUMO

A comprehensive phytochemical study of Juniperus turbinata (Cupressaceae) collected from La Maddalena Archipelago (Sardinia, Italy) is reported. Both the essential oil and the ethanolic extract obtained from the aerial parts were analyzed. The essential oil appears to belong to a new chemotype compared to other Mediterranean juniper accessions, as it was favored by geographic isolation of the isles. It showed a low content of monoterpene hydrocarbons and α-terpineol, ent-manoyl oxide, 1,10-di-epi-cubenol as the major constituents. The ethanolic fraction contained mainly diterpenoids. Among these, 15-formyloxyimbricatolic acid (7) is a new natural product since it has hitherto been obtained only by synthetic route. The phenolic fraction contained biflavonoids: cupressuflavone (9), followed by minor amounts of amentoflavone (10) and hinokiflavone (11). The essential oil and six purified compounds (1 - 4, 8 and 9) were assessed for biological activities, namely antioxidant (assessed by DPPH· , ABTS·+ and FRAP methods) and cytotoxic effects towards selected human tumor cell lines (MDA-MB 231, A375 and HCT116 cells). Compound 3 exhibited higher radical scavenging activity against ABTS·+ radical than the reference Trolox. Noteworthy, compound 8 showed powerful effects towards tumor cell lines, with IC50 values in the range of 0.060 - 0.201 µm, which make it a promising anticancer drug candidate.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Cupressaceae/química , Óleos Voláteis/farmacologia , Compostos Fitoquímicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Radicais Livres/antagonistas & inibidores , Humanos , Itália , Conformação Molecular , Óleos Voláteis/química , Óleos Voláteis/isolamento & purificação , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Relação Estrutura-Atividade
14.
DNA Repair (Amst) ; 60: 89-101, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29112893

RESUMO

Investigation of natural products is an attractive strategy to identify novel compounds for cancer prevention and treatment. Numerous studies have shown the efficacy and safety of natural products, and they have been widely used as alternative treatments for a wide range of illnesses, including cancers. However, it remains unknown whether natural products affect homologous recombination (HR)-mediated DNA repair and whether these compounds can be used as sensitizers with minimal toxicity to improve patients' responses to radiation therapy, a mainstay of treatment for many human cancers. In this study, in order to systematically identify natural products with an inhibitory effect on HR repair, we developed a high-throughput image-based HR repair screening assay and screened a chemical library containing natural products. Among the most interesting of the candidate compounds identified from the screen was ß-thujaplicin, a bioactive compound isolated from the heart wood of plants in the Cupressaceae family, can significantly inhibit HR repair. We further demonstrated that ß-thujaplicin inhibits HR repair by reducing the recruitment of a key HR repair protein, Rad51, to DNA double-strand breaks. More importantly, our results showed that ß-thujaplicin can radiosensitize cancer cells. Additionally, ß-thujaplicin sensitizes cancer cells to PARP inhibitor in different cancer cell lines. Collectively, our findings for the first time identify natural compound ß-thujaplicin, which has a good biosafety profile, as a novel HR repair inhibitor with great potential to be translated into clinical applications as a sensitizer to DNA-damage-inducing treatment such as radiation and PARP inhibitor. In addition, our study provides proof of the principle that our robust high-throughput functional HR repair assay can be used for a large-scale screening system to identify novel natural products that regulate DNA repair and cellular responses to DNA damage-inducing treatments such as radiation therapy.


Assuntos
Monoterpenos/uso terapêutico , Neoplasias/tratamento farmacológico , Rad51 Recombinase/efeitos dos fármacos , Radiossensibilizantes/uso terapêutico , Reparo de DNA por Recombinação/efeitos dos fármacos , Tropolona/análogos & derivados , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Cupressaceae/química , DNA/metabolismo , Quebras de DNA de Cadeia Dupla , Quimioterapia Combinada , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Monoterpenos/farmacologia , Monoterpenos/toxicidade , Neoplasias/enzimologia , Neoplasias/genética , Extratos Vegetais , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Rad51 Recombinase/metabolismo , Radiossensibilizantes/farmacologia , Radiossensibilizantes/toxicidade , Tropolona/farmacologia , Tropolona/uso terapêutico , Tropolona/toxicidade
15.
Anal Bioanal Chem ; 409(15): 3719-3729, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28401286

RESUMO

General emissions of volatile organic compounds from wood are well investigated, but only limited information is available on the odor-active substances contained therein. To close this gap, we aimed at specifically elucidating the odorous constituents of wood from incense cedar [Calocedrus decurrens (Torr.) Florin]; this material is commonly used for the production of a range of products such as pencils and interior accessories. Targeted odorant analysis requires specialized techniques combining modern odorant analytical tools with human-sensory evaluation. Following this concept, the odor profile of the wood sample was first evaluated by human-sensory analyses. Then, the most potent wood odorants were characterized by means of gas chromatography-olfactometry and ranked according to their odor potency via aroma extract dilution analysis. With use of this approach, more than 60 odorous substances were detected, and the 22 most potent odorants were successfully identified by gas chromatography-mass spectrometry/olfactometry and two-dimensional gas chromatography-mass spectrometry/olfactometry. Among the main odorants found were a series of terpenes, several degradation products of fatty acids, and a number of odorants with a phenolic core moiety. Five odorants are reported here for the first time as wood odorants, such as γ-octalactone and 3-phenylpropanoic acid; thymoquinone was demonstrated for the first time to have a pencil-like odor quality.


Assuntos
Cupressaceae/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Odorantes/análise , Olfatometria/métodos , Madeira/química , Adulto , Benzoquinonas/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Orgânicos Voláteis/análise , Adulto Jovem
16.
Food Funct ; 8(1): 86-95, 2017 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-28059416

RESUMO

The flavonoids (POFs) from the leaves of Platycladus orientalis (L.) Franco were purified using six different macroporous adsorption resins including polar resins NKA-9 and ADS-F8, semi-polar resins ADS-17 and AB-8, and non-polar resins D101 and ADS-5. Among semi-polar resins, AB-8 demonstrated the best adsorption and desorption capacities with an adsorption ratio of 86% and a desorption ratio of 52%. According to the Simultaneous Thermogravimetry-Differential Scanning Calorimetry (STA/TG-DSC) analysis, POFs showed three thermally decomposed temperatures (347.6 °C, 437.5 °C and 494.8 °C). The main flavonoids in POFs were identified as esculin, amentoflavone, glabridin, and afromosin. Meanwhile, POFs in the dosage range of 25 to 400 µg mL-1 showed a significant anti-inflammatory effect on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophage cells, which could inhibit the secretion of NO, IL-6, and TNF-α through the inhibition of inflammatory-related gene expressions.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Cupressaceae/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Adsorção , Animais , Anti-Inflamatórios/química , Varredura Diferencial de Calorimetria , Flavonoides/química , Interleucina-6/imunologia , Macrófagos/imunologia , Camundongos , Óxido Nítrico/imunologia , Extratos Vegetais/química , Porosidade , Células RAW 264.7 , Resinas Sintéticas/química
17.
Chem Biodivers ; 14(2)2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27583773

RESUMO

The impact of phenological stages (vegetative, flowering and fruiting stages) on chemical composition, antioxidant, and antimicrobial activities of Tetraclinis articulata (Vahl) Mast. parts essential oils were investigated for the first time. GC and GC/MS analyses pointed to a quantitative variability of components; terpene hydrocarbons derivatives, represented by α-pinene (16.38 ± 0.19 - 31.78 ± 0.35%) and limonene (3.41 ± 0.07 - 9.49 ± 0.14%) as major components, predominate at the vegetative stage, whereas oxygenated derivatives, represented by camphor (16.11 ± 0.23 - 26.17 ± 0.29%) and bornyl acetate (15.21 ± 0.21 - 27.33 ± 0.33%) as major components, predominate at the fruiting stage. Furthermore, our findings showed that the plant parts collected at the fruiting stage possess the highest antioxidant activity and the best antimicrobial activity against the tested microorganisms, than plant parts collected at the vegetative and flowering stages. This highlighted variability reflects the high impact of phenological cycle on chemical composition and biological activities, which led to conclude that we should select essential oils to be investigated carefully depending on phenological stage, in order to have the highest effectiveness of essential oil in terms of biological activities for human health purposes.


Assuntos
Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Cupressaceae/química , Óleos Voláteis/farmacologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Anti-Infecciosos/química , Antioxidantes/química , Bactérias/efeitos dos fármacos , Compostos de Bifenilo/química , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Óleos Voláteis/química , Picratos/química
18.
Planta Med ; 83(6): 574-581, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27776375

RESUMO

Podophyllotoxin, a lignan still extracted from the rhizomes of Podophyllum hexandrum (Berberidaceae), is the starting molecule for the semisynthesis of widely used anticancer drugs such as etoposide. However, this source is threatened by the over-collection of P. hexandrum. Plants belonging to the Linaceae and Cupressaceae families could be attractive alternative sources with species that contain the lignan podophyllotoxin or its precursors and derivatives. Wild flax species, such as Linum flavum, as well as some Juniperus and Callitris species were investigated for their lignan content, and the in vitro antiproliferative capacity of their extracts was assayed on four tumor cell lines. Some of the lignans were detected by LC-HRMS for the first time in these extracts.In addition, lignans purified from these plants and compounds semisynthesized from commercially available podophyllotoxin were tested in terms of their in vitro antiproliferative activity. The genus Juniperus was the most promising given its in vitro antiproliferative effects, which were also observed with extracts from L. flavum and Callitris species.The in vitro antiproliferative effect of the plant extracts studied here appears to correlate well with the contents of the aryltetralin lignan podophyllotoxin and its glycoside as well as with deoxypodophyllotoxin and 6-methoxypodophyllotoxin. The strongest correlation between the lignan content of the extracts and the antiproliferative activity was observed for 6-methoxypodophyllotoxin. Regarding the possibility of producing large renewable amounts of 6-methoxypodophyllotoxin, this molecule could be of interest to produce new anticancer drugs and to bypass the resistance mechanisms against podophyllotoxin-derived drugs.


Assuntos
Antineoplásicos/farmacologia , Cupressaceae/química , Linho/química , Juniperus/química , Lignanas/farmacologia , Extratos Vegetais/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Vias Biossintéticas , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas , Humanos , Lignanas/química , Lignanas/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Podofilotoxina/análogos & derivados , Podofilotoxina/química , Podofilotoxina/isolamento & purificação , Podofilotoxina/farmacologia
19.
Environ Toxicol Pharmacol ; 46: 270-276, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27522546

RESUMO

Although numerous hypotheses have been proposed to prevent chemotherapy-induced alopecia (CIA), effective pharmaceuticals have yet to be developed. In our study, the back hairs of C57BL/6 mice were factitiously removed. These mice were then treated with cedrol or minoxidil daily. Mice with early-stage anagen VI hair follicles were treated with cyclophosphamide (CYP, 125mg/kg) to induce alopecia. The CYP-damaged hair follicles were observed and quantified by using a digital photomicrograph. The results demonstrated that the minoxidil-treated mice suffered from complete alopecia similar to the model 6days after CYP administration. Simultaneously, the cedrol-treated (200mg/kg) mice manifested mild alopecia with 40% suppression. Histological observation revealed that anagen hair follicles of the cedrol-pretreated mice (82.5%) likely provided from damage compared with the sparse and dystrophic hair follicles of the model mice (37.0%). Therefore, the use of topical cedrol can prevent hair follicle dystrophy and provide local protection against CIA.


Assuntos
Alopecia/prevenção & controle , Antineoplásicos Alquilantes/toxicidade , Ciclofosfamida/toxicidade , Terpenos/uso terapêutico , Alopecia/induzido quimicamente , Animais , Cupressaceae/química , Dermatite de Contato/etiologia , Dermatite de Contato/imunologia , Modelos Animais de Doenças , Feminino , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/crescimento & desenvolvimento , Folículo Piloso/patologia , Camundongos Endogâmicos C57BL , Folhas de Planta/química , Sesquiterpenos Policíclicos , Pele/efeitos dos fármacos , Pele/imunologia , Terpenos/administração & dosagem , Terpenos/isolamento & purificação , Terpenos/toxicidade , Testes de Toxicidade Aguda
20.
Chem Biodivers ; 13(12): 1691-1706, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27566837

RESUMO

In the present work, the hydrodistillation (HD) and microwave-assisted hydrodistillation (MAHD) kinetics of essential oil (EO) extracted from Tetraclinis articulata (Vahl) Mast. wood was conducted, in order to assess the impact of extraction time and technique on chemical composition and biological activities. Gas chromatography (GC) and GC/mass spectrometry analyses showed significant differences between the extracted EOs, where each family class or component presents a specific kinetic according to extraction time, technique and especially for the major components: camphene, linalool, cedrol, carvacrol and α-acorenol. Furthermore, our findings showed a high variability for both antioxidant and anti-inflammatory activities, where each activity has a specific effect according to extraction time and technique. The highlighted variability reflects the high impact of extraction time and technique on chemical composition and biological activities, which led to conclude that we should select EOs to be investigated carefully depending on extraction time and technique, in order to isolate the bioactive components or to have the best quality of EO in terms of biological activities and preventive effects in food.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cupressaceae/química , Inibidores Enzimáticos/farmacologia , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/química , Antioxidantes/isolamento & purificação , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Lipoxigenases/metabolismo , Óleos Voláteis/química , Relação Estrutura-Atividade , Fatores de Tempo , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA