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1.
Int J Mol Sci ; 25(9)2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38732184

RESUMO

Today, allergies have become a serious problem. PR-10 proteins are clinically relevant allergens that have the ability to bind hydrophobic ligands, which can significantly increase their allergenicity potential. It has been recently shown that not only the birch pollen allergen Bet v 1 but also the alder pollen allergen Aln g 1, might act as a true sensitizer of the immune system. The current investigation is aimed at the further study of the allergenic and structural features of Aln g 1. By using qPCR, we showed that Aln g 1 was able to upregulate alarmins in epithelial cells, playing an important role in sensitization. With the use of CD-spectroscopy and ELISA assays with the sera of allergic patients, we demonstrated that Aln g 1 did not completely restore its structure after thermal denaturation, which led to a decrease in its IgE-binding capacity. Using site-directed mutagenesis, we revealed that the replacement of two residues (Asp27 and Leu30) in the structure of Aln g 1 led to a decrease in its ability to bind to both IgE from sera of allergic patients and lipid ligands. The obtained data open a prospect for the development of hypoallergenic variants of the major alder allergen Aln g 1 for allergen-specific immunotherapy.


Assuntos
Alérgenos , Antígenos de Plantas , Imunoglobulina E , Proteínas de Plantas , Pólen , Humanos , Pólen/imunologia , Pólen/química , Alérgenos/imunologia , Alérgenos/química , Antígenos de Plantas/imunologia , Antígenos de Plantas/química , Imunoglobulina E/imunologia , Proteínas de Plantas/imunologia , Proteínas de Plantas/química , Alnus/imunologia , Alnus/química
2.
Molecules ; 27(14)2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35889458

RESUMO

In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds' complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70−80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40−60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography−mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.


Assuntos
Alnus , Alnus/química , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Carragenina/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Cromatografia Gasosa-Espectrometria de Massas , Dor/induzido quimicamente , Dor/tratamento farmacológico , Extratos Vegetais/química , Ratos , Ratos Sprague-Dawley
3.
Molecules ; 27(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35566154

RESUMO

The aim of this study was to identify polyphenolic compounds contained in ethanol and water extracts of black alder (Alnus glutinosa L.) acorns and evaluate their anti-cancer and antimicrobial effects. The significant anti-cancer potential on the human skin epidermoid carcinoma cell line A431 and the human epithelial cell line A549 derived from lung carcinoma tissue was observed. Aqueous and ethanolic extracts of alder acorns inhibited the growth of mainly Gram-positive microorganisms (Staphylococcus aureus, Bacillus subtilis, Streptococcus mutans) and yeast-like fungi (Candida albicans, Candida glabrata), as well as Gram-negative (Escherichia coli, Citrobacter freundii, Proteus mirabilis, Pseudomonas aeruginosa) strains. The identification of polyphenols was carried out using an ACQUITY UPLC-PDA-MS system. The extracts were composed of 29 compounds belonging to phenolic acids, flavonols, ellagitannins and ellagic acid derivatives. Ellagitannins were identified as the predominant phenolics in ethanol and aqueous extract (2171.90 and 1593.13 mg/100 g DM, respectively) The results may explain the use of A. glutinosa extracts in folk medicine.


Assuntos
Alnus , Ilex , Alnus/química , Antibacterianos/química , Antibacterianos/farmacologia , Escherichia coli , Etanol/farmacologia , Humanos , Taninos Hidrolisáveis/farmacologia , Testes de Sensibilidade Microbiana , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Água/farmacologia
4.
J Chem Ecol ; 47(7): 680-688, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34101117

RESUMO

Past work shows a significant negative correlation between foliar oregonin concentration and western tent caterpillar (Malacosoma californicum Packard) feeding on red alder (Alnus rubra Bong.). Above an oregonin threshold of 20% leaf dry weight, little feeding by caterpillars is observed. Concentrations of defensive chemicals are influenced by plant genotype, environmental conditions, insect feeding, and the interactions of these factors. Our objective was to measure the effects of nitrogen (N) availability and wounding on foliar oregonin and condensed tannin concentrations in red alder genotypes. One-year-old seedlings from 100 half-sib red alder families were treated with two levels of ammonium nitrate (NH4NO3) for two growing seasons in a common garden. In the second year, leaves from 50 families from the fertilization experiment were used in a bioassay feeding experiment to determine the effects of N fertilization and genotype on WTC damage, and to identify a subset of 20 families with a range of damage to analyze for phytochemical composition. In separate experiments, wound-induction treatments were conducted outdoors and, in a greenhouse using the N treated trees in their third and fourth year, respectively. Foliar condensed tannin, oregonin and N concentrations were measured and ranked among the plant genotypes, and between the two N treatments and two wounding treatments. Results showed that oregonin and condensed tannin concentrations varied among the alder genotypes. Leaf N concentration was negatively correlated with concentration of oregonin. Neither of the measured phenolic compounds responded to wounding. The results suggest that red alder foliar oregonin and condensed tannin are likely constitutive defenses that are largely determined by genotype, and that the negative correlation of defense compounds with plant internal N status holds in this N-fixing tree.


Assuntos
Alnus/química , Diarileptanoides/química , Mariposas/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Taninos/análise , Alnus/genética , Alnus/crescimento & desenvolvimento , Animais , Cromatografia Líquida de Alta Pressão , Diarileptanoides/farmacologia , Fertilizantes/análise , Genótipo , Herbivoria/efeitos dos fármacos , Larva/efeitos dos fármacos , Larva/fisiologia , Mariposas/crescimento & desenvolvimento , Mariposas/fisiologia , Nitrogênio/química , Nitrogênio/metabolismo , Compostos Fitoquímicos/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Plântula , Espectrofotometria Ultravioleta , Taninos/farmacologia
5.
Molecules ; 26(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201712

RESUMO

Alnus sibirica (AS) is distributed in Korea, Japan, China, and Russia and has reported anti-oxidant, anti-inflammatory, and reducing activities on atopic dermatitis-like skin lesions, along with other beneficial health properties. In the present study, we tried to prove the cancer-preventive activity against prostate cancer. The extracted and isolated compounds, oregonin (1), hirsutenone (2), and hirsutanonol (3), which were isolated from AS, were tested for anti-proliferative activity. To do this, we used the MTT assay; NF-κB inhibitory activity, using Western blotting; apoptosis-inducing activity using flow cytometry; DNA methylation activity, using methylation-specific polymerase chain reaction in androgen-dependent (LNCaP) and androgen-independent (PC-3) prostate cancer cell lines. The compounds (1-3) showed potent anti-proliferative activity against both prostate cancer cell lines. Hirsutenone (2) exhibited the strongest NF-κB inhibitory and apoptosis-inducing activities compared with oregonin (1) and hirsutanonol (3). DNA methylation activity, which was assessed for hirsutenone (2), revealed a concentration-dependent enhancement of the unmethylated DNA content and a reduction in the methylated DNA content in both PC-3 and LNCaP cells. Overall, these findings suggest that hirsutenone (2), when isolated from AS, may be a potential agent for preventing the development or progression of prostate cancer.


Assuntos
Alnus/química , Apoptose/efeitos dos fármacos , Catecóis/farmacologia , Proliferação de Células/efeitos dos fármacos , Desmetilação do DNA/efeitos dos fármacos , Diarileptanoides/farmacologia , Glutationa S-Transferase pi/metabolismo , Neoplasias da Próstata/prevenção & controle , Androgênios/farmacologia , Catecóis/química , Catecóis/isolamento & purificação , Linhagem Celular Tumoral , Diarileptanoides/química , Diarileptanoides/isolamento & purificação , Citometria de Fluxo , Humanos , Masculino , NF-kappa B/metabolismo , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/metabolismo
6.
Biochem Biophys Res Commun ; 526(2): 300-305, 2020 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-32209256

RESUMO

Relationship between autophagy and endoplasmic reticulum (ER) stress and their application to treat cancer have been actively studied these days. Recently, a lignan [(-)-(2R, 3R)-1,4-O-diferuloylsecoisolariciresinol, DFS] from Alnus japonica has been found to reduce the viability of colon cancer cells. In this study, we have observed DFS-induced autophagy in a variety of cancer cell lines. In addition, DFS led to ER stress, based on the activation of unfolded protein response (UPR) transducers and an elevated expression of UPR target genes in prostate and colon cancer cells. Further investigation has shown that DFS triggered the activation of AMP-activated protein kinase (AMPK) signaling and nuclear translocation of transcription factor EB (TFEB). Furthermore, the cytotoxicity of DFS was potentiated by the co-treatment of autophagy inhibitor in these cancer cells. This study has provided a noble implication that the combination of DFS and autophagy inhibition exerts a synergistic effect in cancer treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Autofagia/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Lignanas/farmacologia , Neoplasias/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/metabolismo , Alnus/química , Linhagem Celular Tumoral , Humanos , Neoplasias/metabolismo , Resposta a Proteínas não Dobradas/efeitos dos fármacos
7.
Molecules ; 25(6)2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32244969

RESUMO

Alnus sibirica extracts (ASex) have long been used in Oriental medicine to treat various conditions. To provide a scientific basis for this application and the underlying mechanism, we investigated the anti-inflammatory effects of ASex in vitro and in vivo. The in vitro model was established using human dermal fibroblasts (HDFs) treated with inflammatory stimulants (lipopolysaccharide, tumor necrosis factor-alpha, interferon-gamma). Lactate dehydrogenase and reverse transcription-polymerase chain reaction showed that ASex inhibited the increased expression of acute-phase inflammatory cytokines. The in vivo model was established by inducing skin inflammation in NC/Nga mice via the repeated application of house dust mite (HDM) ointment to the ears and back of the mice for eight weeks. HDM application increased the severity of skin lesions, eosinophil/mast cell infiltration, and serum immunoglobulin E levels, which were all significantly decreased by ASex treatment, demonstrating the same degree of protection as hydrocortisone. Overall, ASex showed excellent anti-inflammatory effects both in vitro and in vivo, suggesting its potential as an excellent candidate drug to reduce skin inflammation.


Assuntos
Alnus/química , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Animais , Biópsia , Cromatografia Líquida de Alta Pressão , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Derme/citologia , Derme/efeitos dos fármacos , Derme/metabolismo , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Imunoglobulina E/sangue , Mediadores da Inflamação/metabolismo , Camundongos
8.
Molecules ; 25(5)2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32121012

RESUMO

JNK and p38 are important mitogen-activated protein kinases (MAPKs) that respond to stress stimuli. The stress-activated MAPKs associated with apoptotic cell death play vital roles in mammalian cells. Alnus hirsuta, which contains abundant diarylheptanoids derivatives, is a valuable medicinal plant. The CHCl3 extract (AHC) containing platyphyllenone (1) and platyphyllone (3) as main compounds showed in vitro anticancer effects. We report the biological activities of A. hirsuta extract associated with the regulation of apoptosis and JNK and p38 in MCF-7 breast cancer cells. Levels of phospho-JNK and phospho-p38 by AHC treatment were evaluated by enzyme-linked immunosorbent assay (ELISA). ROS production, apoptotic effect, and DNA contents of the cells were measured by flow cytometry. The two diarylheptanoids 1 and 3 and the AHC extract exhibited cytotoxic effects on MCF-7 cells in MTT assay, with IC50 values of 18.1, 46.9, 260.0 µg/mL, respectively. AHC induced ROS generation and elevated the endogenous levels of phospho-JNK and phospho-p38. AHC resulted in apoptosis and cell cycle arrest. We suggest that the antitumor effect of A. hirsuta extract is achieved by apoptosis promotion and cell cycle arrest mediated by the activation of JNK and p38 signaling pathway via ROS generation.


Assuntos
Alnus/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Diarileptanoides/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Extratos Vegetais/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos
9.
Molecules ; 25(15)2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32717959

RESUMO

In the present study, we isolated a lignan ((-)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS) from Alnus japonica and evaluated its antiobesity potential in vitro. We also determined its mechanism of action in a mouse pre-adipocyte 3T3-L1 cell line. DFS dose- and day-dependently inhibited adipogenesis by downregulation of adipogenic factors and lipid metabolism-regulating factors during adipocyte differentiation. In particular, DFS suppressed cell cycle-regulating factors and induced G0/G1 cell cycle arrest, implying that it had an inhibitory effect on mitotic clonal expansion which occurred at an early stage of adipogenesis. DFS also suppressed adipogenesis through decreasing Akt phosphorylation and increasing the level of Forkhead box protein-O1 (FOXO1). These results suggest that DFS may be a pharmacological candidate for the development of antiobesity, therapeutic, and nutraceutical products.


Assuntos
Adipogenia/efeitos dos fármacos , Alnus/química , Proteína Forkhead Box O1/metabolismo , Lignanas/farmacologia , Regulação para Cima , Células 3T3-L1 , Animais , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo
10.
Anal Bioanal Chem ; 411(28): 7573-7583, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31642944

RESUMO

Desorption atmospheric pressure photoionization (DAPPI) is an ambient mass spectrometry (MS) technique that allows the analysis of both polar and nonpolar compounds directly from the surfaces of various sample types. Here, DAPPI was used to study the chemical profiles in different parts of birch and alder tree barks. Four distinct fractions of Betula pendula (silver birch) bark were collected from three different developmental stages of the stem, after which the chemical profiles of the different tissue types were measured. Of special interest were triterpenoids, a class of important defensive substances, which are found in the bark of the silver birch. Additionally, the chemical profiles of lenticels and the surrounding surfaces in the phellem of B. pendula (silver birch), Alnus glutinosa (black alder), and Alnus incana (gray alder) were screened with DAPPI. Another ambient MS technique, laser ablation atmospheric pressure photoionization (LAAPPI), was further used for the mass spectrometry imaging of lenticels on the B. pendula phellem. All the studied birch bark fractions showed individual chemical profiles in DAPPI. The mass spectra from the young apical stem and the transition zone resembled each other more than the mature stem. Instead, the phellem was found to contain a high amount of triterpenoids in all the developmental stages of the stem. The most intense peaks in the DAPPI mass spectra of the birch bark fractions were those of betulin and lupeol. Betulinic and betulonic acid peaks were intense as well, and these compounds were detected especially in the lenticels of the tree samples. Graphical abstract.


Assuntos
Alnus/química , Betula/química , Espectrometria de Massas/métodos , Casca de Planta/química
11.
Chem Biodivers ; 16(9): e1900314, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31397975

RESUMO

In this study, we investigated the phenolic composition of the crude extract (MeOH 80 %) of Alnus cordata (Loisel.) Duby stem bark (ACE) and its antioxidant and skin whitening properties. RP-LC-DAD analysis showed a high content of hydroxycinnamic acids (47.64 %), flavanones (26.74 %) and diarylheptanoids (17.69 %). Furthermore, ACE exhibited a dose-dependent antioxidant and free-radical scavenging activity, expressed as half-maximal inhibitory concentration (IC50 ): Oxygen radical absorbance capacity (ORAC, IC50 1.78 µg mL-1 )>Trolox equivalent antioxidant capacity (TEAC, IC50 3.47 µg mL-1 )>2,2-Diphenyl-1-picrylhydrazyl (DPPH, IC50 5.83 µg mL-1 )>ß-carotene bleaching (IC50 11.58 µg mL-1 )>Ferric reducing antioxidant power (FRAP, IC50 17.28 µg mL-1 ). Moreover, ACE was able to inhibit in vitro tyrosinase activity (IC50 77.44 µg mL-1 ), l-DOPA auto-oxidation (IC50 39.58 µg mL-1 ) and in an in vivo model it exhibited bleaching effects on the pigmentation of zebrafish embryos (72 h post fertilization) without affecting their development and survival. In conclusion, results show that A. cordata stem bark may be considered a potential source of agents for the treatment of skin disorders due to its bleaching properties and favorable safety profiles, associated to a good antioxidant power.


Assuntos
Alnus/química , Antioxidantes/farmacologia , Inibidores Enzimáticos/farmacologia , Polifenóis/farmacologia , Pele/efeitos dos fármacos , Animais , Antioxidantes/química , Antioxidantes/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Picratos/antagonistas & inibidores , Casca de Planta/química , Extratos Vegetais/química , Polifenóis/química , Polifenóis/isolamento & purificação , Peixe-Zebra
12.
Molecules ; 24(10)2019 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-31137531

RESUMO

Alnus sibirica (AS) is geographically distributed in Korea, Japan, Northeast China, and Russia. Various anti-oxidant, anti-inflammation, anti-atopic dermatitis and anti-cancer biological effects of AS have been reported. Enzymatic hydrolysis decomposes the sugar bond attached to glycoside into aglycone which, generally, has a superior biological activity, compared to glycoside. Enzymatic hydrolysis of the extract (EAS) from AS was processed and the isolated compounds were investigated-hirsutanonol (1), hirsutenone (2), rubranol (3), and muricarpon B (4). The structures of these compounds were elucidated, and the biological activities were assessed. The ability of EAS and the compounds (1-4) to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals and Nitroblue tetrazolium (NBT) superoxide, and to inhibit NO production was evaluated in vitro. EAS showed more potent antioxidant and anti-inflammatory activity than AS. All investigated compounds showed excellent antioxidant and anti-inflammatory activities.


Assuntos
Alnus/química , Compostos de Bifenilo/metabolismo , Diarileptanoides/isolamento & purificação , Etanol/química , Óxido Nítrico/biossíntese , Nitroazul de Tetrazólio/metabolismo , Picratos/metabolismo , Extratos Vegetais/química , Superóxidos/metabolismo , Animais , Hidrólise , Concentração Inibidora 50 , Camundongos , Células RAW 264.7
13.
Molecules ; 24(16)2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31398908

RESUMO

The effects of Alnus sibirica (AS) extracts on cytokine expression induced by inflammatory stimulants were examined in human dermal fibroblasts (HDFs) and RAW264.7 cells. The anti-oxidative effect and effect on cell viability of AS extracts were evaluated, and four extracts with the highest anti-oxidative effects were selected. HDFs and RAW264.7 cells were treated with inflammatory stimulants, and the expression of cytokines involved in acute (IL-6 and IL-10) and chronic (IL-18) inflammation, the initiation of the immune response (IL-33), and non-specific immune responses (IL-1ß, IL-8, and TNF-α) were determined using a reverse-transcription polymerase chain reaction. LPS increased the expression of all the cytokines, except for IL-18; however, AS extracts, particularly AS2 and AS4, reduced this increase, and TNF-α treatment markedly increased the expression of cytokines related to non-specific immune responses. IFN-γ treatment induced no significant changes, except for increased IL-33 expression in HDFs. AS extracts inhibited the increase in the expression of IL-33 and other cytokines in HDFs. Thus, the exposure of HDFs and RAW264.7 cells to inflammatory stimulants increased the expression of cytokines related to all the inflammatory processes. HDFs are involved not only in simple tissue regeneration but also in inflammatory reactions in the skin. AS2 and AS4 may offer effective therapy for related conditions.


Assuntos
Alnus/química , Citocinas/genética , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Extratos Vegetais/farmacologia , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Interferon gama/metabolismo , Interferon gama/farmacologia , Lipopolissacarídeos , Camundongos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/química , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia
14.
J Enzyme Inhib Med Chem ; 33(1): 1055-1063, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29877148

RESUMO

Oregonin is an open-chain diarylheptanoid isolated from Alnus incana bark that possesses remarkable antioxidant and anti-inflammatory properties, inhibits adipogenesis, and can be used in the prevention of obesity and related metabolic disorders. Here, we aimed to investigate the effects of oregonin on the epigenetic regulation in cells as well as its ability to modulate DNA methylating enzymes expression and mitochondrial DNA (mtDNA) copies. Our results show that oregonin altered the expression of DNA methyltransferases and mtDNA copy numbers in dependency on concentration and specificity of cells genotype. A close correlation between mtDNA copy numbers and mRNA expression of the mtDnmt1 and Dnmt3b was established. Moreover, molecular modeling suggested that oregonin fits the catalytic site of DNMT1 and partially overlaps with binding of the cofactor. These findings further extend the knowledge on oregonin, and elucidate for the first time its potential to affect the key players of the DNA methylation process, namely DNMTs transcripts and mtDNA.


Assuntos
Alnus/química , DNA (Citosina-5-)-Metiltransferase 1/biossíntese , DNA (Citosina-5-)-Metiltransferases/biossíntese , DNA Mitocondrial/metabolismo , Diarileptanoides/farmacologia , Fibroblastos/efeitos dos fármacos , Casca de Planta/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA/efeitos dos fármacos , Diarileptanoides/química , Diarileptanoides/isolamento & purificação , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Relação Estrutura-Atividade , DNA Metiltransferase 3B
15.
Molecules ; 23(2)2018 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-29463011

RESUMO

Phytochemical isolation of fermented Alnus sibirica (FAS) which was produced by using Lactobacillus plantarum subsp. argentoratensis, exhibited multiple and different composition compared with the original plant. Anti-allergic contact dermatitis (anti-ACD)/anti-atopic dermatitis (anti-AD) activities (visual observation and regulation of Th1/Th2 cytokines and IgE in blood) of FAS and the barks of Alnus sibirica extract (AS) and the two diarylheptanoids, hirsutenone (1) and muricarpon B (2), which are major components of FAS, were measured in vitro and in vivo. FAS, AS and the two compounds showed potent anti-oxidative, anti-inflammatory, anti-ACD and anti-AD activity. In particular, FAS showed more potent biological activity than AS. Thus, fermentation might be a prominent way to enhance the biological activity compared with the original plant. In addition, compounds (1) and (2) might be developed as functional materials or herbal medicines for ACD and AD.


Assuntos
Alnus/química , Dermatite Alérgica de Contato/tratamento farmacológico , Dermatite Atópica/tratamento farmacológico , Extratos Vegetais/farmacologia , Administração Oral , Animais , Catecóis/química , Catecóis/isolamento & purificação , Diarileptanoides/química , Diarileptanoides/isolamento & purificação , Fermentação , Humanos , Inflamação/tratamento farmacológico , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Casca de Planta/química , Extratos Vegetais/química
16.
Cutan Ocul Toxicol ; 37(3): 210-217, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29216751

RESUMO

CONTEXT: Contact with pollen is the major reason for the development of allergic symptoms on the ocular surface leading to a significant increase of allergic diseases worldwide. Environmental changes such as increased ultraviolet (UV) radiation and air pollution are discussed as contributory causes for this increase. OBJECTIVE: We investigated the effect of UV light on the histamine content of pollen and examined if an irradiation of pollen affects the viability and proliferation of conjunctival cells. MATERIALS AND METHODS: Alder (Alnus glutinosa) and hazel (Corylus avellana) pollen were irradiated for different time periods with sunlight, UV-A or UV-B light and the histamine content was analysed and compared with non-irradiated pollen. Conjunctival epithelial cells (CHANG cells) were exposed to irradiated and non-irradiated pollen followed by an assessment of cell viability with the colorimetric MTS test and the impedance-based measurement of cell proliferation using the xCELLigence real-time analysis system. RESULTS: UV light irradiation increased the histamine level of alder and hazel pollen in a dose-dependent manner. CHANG cells treated with irradiated pollen induced a statistically significant higher decrease of cell viability than treatment with non-irradiated pollen. DISCUSSION AND CONCLUSIONS: Our results indicate that UV light is able to alter pollen thus making them more harmful for conjunctival cells.


Assuntos
Alérgenos/imunologia , Conjuntivite Alérgica/imunologia , Histamina/imunologia , Pólen/imunologia , Raios Ultravioleta/efeitos adversos , Alérgenos/efeitos da radiação , Alnus/química , Alnus/imunologia , Alnus/efeitos da radiação , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/imunologia , Túnica Conjuntiva/citologia , Túnica Conjuntiva/imunologia , Corylus/química , Corylus/imunologia , Corylus/efeitos da radiação , Relação Dose-Resposta à Radiação , Células Epiteliais/imunologia , Histamina/efeitos da radiação , Humanos , Pólen/química , Pólen/efeitos da radiação
17.
J Nat Prod ; 80(5): 1255-1263, 2017 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-28368586

RESUMO

Seven derivatives of pentacyclic triterpene acids (1-7) were isolated from the bark of Alnus viridis ssp. viridis using a combination of column chromatography and semipreparative HPLC. Compounds 1-3, 6, and 7 were determined to be new after spectroscopic data interpretation and were assigned as 27-hydroxyalphitolic acid derivatives (1-3), a 27-hydroxybetulinic acid derivative (6), and a 3-epi-maslinic acid derivative (7), respectively. Pentacyclic triterpenoids with a C-27 hydroxymethyl group have been found in species of the genus Alnus for the first time. These compounds were subjected to cytotoxicity testing against a number of cancer cell lines. Also, selected pentacyclic triterpenoids were selected as potential inhibitors of topoisomerases I and IIα for an in silico investigation.


Assuntos
Linhagem Celular/efeitos dos fármacos , Triterpenos Pentacíclicos/isolamento & purificação , Triterpenos Pentacíclicos/farmacologia , Casca de Planta/química , Inibidores da Topoisomerase/isolamento & purificação , Inibidores da Topoisomerase/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Alnus/química , Linhagem Celular/química , Humanos , Estrutura Molecular , Triterpenos Pentacíclicos/química , Inibidores da Topoisomerase/química , Triterpenos/química
18.
Biol Pharm Bull ; 40(9): 1544-1550, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28867736

RESUMO

Alnus japonica (Betulaceae) is a broad-leaved tree easily found in damp regions within the mountains of Korea and Japan. Four triterpenoids (1-4) from the fruits of A. japonica, including the newly isolated 3ß-hydroxy-lanost-9(11),23(24)-dien-25,26-diol (3), inhibited the lipopolysaccharide (LPS)-induced expression of the chemotactic cytokine interleukin (IL)-8 and nitric oxide (NO) production in HT-29 colon epithelial cells and RAW264.7 macrophages, respectively. Among these triterpenoids, compound 4, which showed the most potent inhibitory activity, effectively down-regulated LPS-induced protein expression of inducible nitric oxide synthase (iNOS) in RAW264.7 cells and in HT-29 cells. Also, compound 4 concentration-dependently inhibited the levels of LPS-induced pro-inflammatory cytokines, IL-1ß and IL-6 in macrophage cells. These triterpenoids isolated from A. japonica fruits are thought to contribute to the anti-inflammatory activities of macrophage and colon epithelial cells, which are important for regulating the colon immune system. They are expected to be potential candidates for therapeutic agents against inflammatory bowel disease.


Assuntos
Alnus/química , Anti-Inflamatórios não Esteroides/farmacologia , Lipopolissacarídeos/antagonistas & inibidores , Triterpenos/farmacologia , Animais , Citocinas/biossíntese , Frutas/química , Células HT29 , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Interleucina-6/biossíntese , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Células RAW 264.7 , Relação Estrutura-Atividade , Triterpenos/isolamento & purificação
19.
Biol Pharm Bull ; 40(5): 630-637, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28458348

RESUMO

The aim of the present study was to examine the inhibitory roles and mechanisms of hirsutenone (HTN) in the regulation of osteoclastogenesis. Gene levels were compared to assure the effects of HTN on osteoclastogenesis in mouse splenocytes/CD4+ T cells, mouse macrophage-like cell line RAW264.7 (preosteoclast), MG63 (osteoblast), and RPMI1788 (B cell) cells. The mechanism by which HTN regulates the degradation of tumor necrosis factor receptor-associated factor 6 (TRAF6) and inhibits inhibitor of kappaB (IκB) and nuclear factor-kappaB (NF-κB) signaling was examined by Western blotting and luciferase reporter assays. Our results demonstrated that HTN effectively downregulated the expression of interferon γ (IFNγ), interleukin-22 (IL-22), IL-1ß, and tartrate-resistant acid phosphatase (TRAP) in splenocyte-/CD4+-RAW264.7 co-culture system. Moreover, receptor activator of nuclear factor-κB ligand (RANKL) and CD25 expression were also significantly inhibited in MG63 and CD4+ single culture system, suggesting an additional independent effect of HTN on osteoclastogenesis. Notably, TRAF6 was markedly degraded along with a decrease in nuclear factor of activated T-cells (NFATc) and NF-κB activities in RAW264.7 cells. Finally, we concluded that HTN directly or indirectly inhibits osteoclastogenesis via the inhibition of NF-κB signaling by promoting TRAF6 degradation, and plays a crucial role in suppressing the expression of RANKL and cytokines expressed in IFNγ-producing T-helper 1 (Th1) cells. These findings suggest that HTN may be a promising therapeutic candidate for diseases resulting from bone loss.


Assuntos
Catecóis/farmacologia , Diarileptanoides/farmacologia , Interferon gama/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Osteoclastos/efeitos dos fármacos , Células Th1/efeitos dos fármacos , Alnus/química , Animais , Linfócitos T CD4-Positivos/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/antagonistas & inibidores , Citocinas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Osteogênese/efeitos dos fármacos , Casca de Planta/química , Ligante RANK/genética , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos , Baço/química , Baço/citologia , Células-Tronco/efeitos dos fármacos , Fosfatase Ácida Resistente a Tartarato/biossíntese , Fosfatase Ácida Resistente a Tartarato/genética
20.
Planta Med ; 83(1-02): 117-125, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27220074

RESUMO

Diarylheptanoids from the barks of Alnus viridis ssp. viridis (green alder) and Alnus glutinosa (black alder) were explored for anti-quorum sensing activity. Chemicals with anti-quorum sensing activity have recently been examined for antimicrobial applications. The anti-quorum sensing activity of the selected diarylheptanoids was determined using two biosensors, namely Pseudomonas aeruginosa PAO1 and Chromobacterium violaceum CV026. Although all of the investigated compounds negatively influenced the motility of P. aeruginosa PAO1, four were able to inhibit biofilm formation of this human opportunistic pathogen for 40-70 %. Three of the diarylheptanoids (3, 4, and 5) negatively influenced the biosynthesis of pyocyanin, which is under the control of quorum sensing. Platyphyllenone (7) and hirsutenone (5) were able to inhibit the biosynthesis of violacein in C. violaceum CV026, with 5 being able to inhibit the synthesis of both biopigments. Only one of the tested diarylheptanoids (1) was shown to significantly decrease the production of acyl homoserine lactones (AHL) in P. aeruginosa PAO1, more specifically, production of the long chain N-(3-oxododecanoyl)-l-HSL. On the other side, four diarylheptanoids (2-5) significantly reduced the synthesis of 2-alkyl-4-quinolones, part of the P. aeruginosa quinolone-mediated signaling system. To properly assess therapeutic potential of these compounds, their in vitro antiproliferative effect on normal human lung fibroblasts was determined, with doses affecting cell proliferation between 10 and 100 µg/mL. This study confirms that the barks of green and black alders are rich source of phytochemicals with a wide range of biological activities that could further be exploited as natural agents against bacterial contaminations and infections.


Assuntos
Alnus/química , Chromobacterium/efeitos dos fármacos , Diarileptanoides/farmacologia , Extratos Vegetais/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Acil-Butirolactonas/metabolismo , Antibacterianos/farmacologia , Catecóis/metabolismo , Chromobacterium/metabolismo , Diarileptanoides/química , Diarileptanoides/isolamento & purificação , Diarileptanoides/metabolismo , Humanos , Indóis/metabolismo , Casca de Planta/química , Pseudomonas aeruginosa/metabolismo , Piocianina/metabolismo
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