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1.
Appl Microbiol Biotechnol ; 103(20): 8351-8361, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31392378

RESUMO

This study describes the application of in situ extractive fermentation (ISEF) to increase the yields of antroquinonol (AQ) and antrodin C (AC) from Antrodia camphorata S-29. In initial screening experiments, nine solvents were tested to identify the most suitable extractant for the in situ extraction of AQ and AC. These solvents included n-tetradecane, n-dodecane, n-decane, heavy paraffin, light paraffin, oleyl alcohol, oleic acid, butyl oleate, and isopropyl myristate. Of these, oleic acid was the most suitable solvent for the in situ extraction of AQ and AC. The use of oleic acid as an in situ extractant significantly improved AQ and AC productions, which were approximately 5-fold and 8-fold that of the control, respectively. The recovered oleic acid was treated with a silica gel solid-phase extraction column, which was able to rapidly adsorb the bioactive metabolites. The separated solvent hardly contained fermentation products and could be directly reused in ISEF. AQ and AC were obtained with purities of over 75% by silica gel column chromatography. The recoveries of AQ and AC reached 70.7 ± 0.8% and 81.5 ± 1.2%, respectively.


Assuntos
Antrodia/metabolismo , Maleimidas/isolamento & purificação , Maleimidas/metabolismo , Ubiquinona/análogos & derivados , Biotecnologia/métodos , Fermentação , Solventes/metabolismo , Ubiquinona/isolamento & purificação , Ubiquinona/metabolismo
2.
Appl Microbiol Biotechnol ; 103(19): 7843-7867, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31407039

RESUMO

Antrodia camphorata, also known as A. cinnamomea, is a precious medicinal basidiomycete fungus endemic to Taiwan. This article summarizes the recent advances in research on the multifarious pharmacological effects of A. camphorata. The mushroom exhibits anticancer activity toward a large variety of cancers including breast, cervical, ovarian, prostate, bladder, colorectal, pancreatic, liver, and lung cancers; melanoma; leukemia; lymphoma; neuroblastoma; and glioblastoma. Other activities encompass antiinflammatory, antiatopic dermatitis, anticachexia, immunoregulatory, antiobesity, antidiabetic, antihyperlipidemic, antiatherosclerotic, antihypertensive, antiplatelet, antioxidative, antiphotodamaging, hepatoprotective, renoprotective, neuroprotective, testis protecting, antiasthmatic, osteogenic, osteoprotective, antiviral, antibacterial, and wound healing activities. This review aims to provide a reference for further development and utilization of this highly prized mushroom.


Assuntos
Antrodia/classificação , Antrodia/metabolismo , Produtos Biológicos/metabolismo , Variação Genética , Tecnologia Farmacêutica/métodos , Antrodia/genética , Taiwan
3.
Phytother Res ; 33(9): 2288-2297, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31359520

RESUMO

Parkinson's disease (PD) is a neurodegenerative disease, and the role of neuroinflammation in the pathogenesis and progression of PD has been confirmed. The polysaccharides and triterpenoids of antrodia camphorata (a polyporous fungus) harbor diverse and powerful pharmacological effects. In this study, 6-hydroxydopamine was used to construct a PD mouse model. After antrodia camphorata polysaccharide (ACP) intervention, neurobehavioral changes were detected, neurotransmitter changes in striatum were determined by high-performance liquid chromatography, the alterations of striatal NOD-like receptor pyrin domain containing three (NLRP3) were examined by immunohistochemistry, and the expression of NLRP3, IL-1ß, Caspase-1, and proCaspase-1 were detected by western blot. To be specific, the items of neurobehavioral test included open field activity, rotary test, pole test, gait analysis, and swimming test. As a result, 6-hydroxydopamine could lead to PD-like lesions, including tremor, stiffness, attenuated spontaneous activity, and bradykinesia in mice, and the expression of tyrosine hydroxylase in the striatum was decreased. After ACP intervention, the neuroethology of mice was significantly improved, as demonstrated by the elevated levels of dopamine in the striatum and the decreased expression of dopamine in the striatum in NLRP3 inflammasome. NLRP3 inflammasome played an important role in neuroinflammation in PD mice. ACP could reduce the activation of NLRP3 and expression of related inflammatory factors.


Assuntos
Antrodia/metabolismo , Inflamassomos/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doença de Parkinson/tratamento farmacológico , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos NOD , Doenças Neurodegenerativas/patologia , Doença de Parkinson/patologia , Polissacarídeos
4.
Carbohydr Polym ; 216: 204-212, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31047058

RESUMO

Sulfated polysaccharides (SPSs) are polysaccharides (PSs) with high sulfate functionalization and possess bioactivities. This study aimed to increase the sulfate content of SPSs in Antrodia cinnamomea through sulfate feeding. Feeding A. cinnamomea with sodium thiosulfate was found to increase yields of PSs and SPSs in A. cinnamomea. The SPSs thus obtained (ST-SPS) were further isolated, showing enhanced sulfate content of 2.5 mmol/g. Sodium thiosulfate induced changes in molecular weight from 320 kDa to 1342 kDa, and area percentage of low-molecular-weight ST-SPS (< 20 kDa) was decreased. Functional studies revealed that sodium thiosulfate increased the ST-SPS anticancer efficacy in cancer cells via inhibition of EGFR/AKT signaling. Moreover, the ST-SPS enhanced synergistically cisplatin-, gefitinib- and 5 FU-induced cytotoxic effects in lung cancer H1975 cells and colon cancer CT26 cells. This study is the first to demonstrate that sodium thiosulfate induced changes in properties of A. cinnamomea with the anticancer mechanisms of ST-SPS.


Assuntos
Antineoplásicos/farmacologia , Antrodia/química , Antrodia/metabolismo , Polissacarídeos/farmacologia , Ésteres do Ácido Sulfúrico/farmacologia , Tiossulfatos/metabolismo , Animais , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Cisplatino/farmacologia , Sinergismo Farmacológico , Receptores ErbB/metabolismo , Fluoruracila/farmacologia , Gefitinibe/farmacologia , Humanos , Concentração Inibidora 50 , Camundongos , Peso Molecular , Fosforilação/efeitos dos fármacos , Polissacarídeos/biossíntese , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Ésteres do Ácido Sulfúrico/química , Ésteres do Ácido Sulfúrico/isolamento & purificação , Ésteres do Ácido Sulfúrico/metabolismo
5.
Phytochemistry ; 161: 97-106, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30822625

RESUMO

Antrodia cinnamomea, an endemic fungus species of Taiwan, has long been used as a luxurious dietary supplement to enhance liver functions and as a remedy for various cancers. Antroquinonol (AQ), identified from the mycelium of A. cinnamomea, is currently in phase II clinical trials in the USA and Taiwan for the treatment of non-small-cell lung cancer. In the previous studies, we have demonstrated that AQ and 4-acetylantroquinonol B (4-AAQB) utilize orsellinic acid, via polyketide pathway, as the ring precursor, and their biosynthetic sequences are similar to those of coenzyme Q. In order to test 4-hydroxybenzoic acid (4-HBA), synthesized via shikimate pathway, is the ring precursor of AQ analogs, the strategy of metabolic labeling with stable isotopes was applied in this study. Here we have confirmed that 4-HBA serves as the ring precursor for AQ but not a precursor of 4-AAQB. Experimental results indicated that A. cinnamomea preferentially utilizes endogenous 4-HBA via shikimate pathway for AQ biosynthesis. Exogenous tyrosine and phenylalanine can be utilized for AQ biosynthesis when shikimate pathway is blocked by glyphosate. The benzoquinone ring of 4-AAQB is synthesized only via polyketide pathway, but that of AQ is synthesized via both polyketide pathway and shikimate pathway. The precursor-products relationships diagram of AQ and 4-AAQB in A. cinnamomea are proposed based on the experimental findings.


Assuntos
Antrodia/química , Parabenos/metabolismo , Ubiquinona/análogos & derivados , Antrodia/metabolismo , Estrutura Molecular , Parabenos/química , Ubiquinona/biossíntese , Ubiquinona/química
6.
Carbohydr Polym ; 205: 271-278, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30446105

RESUMO

Carbon and nitrogen sources in culture medium of Antrodia cinnamomea were optimized to eliminate the interference of exterior macromolecules on exopolysaccharide (EPS) yield by submerged fermentation. The results suggested that culture medium containing 50 g/L of glucose and 20 g/L of yeast extract as the optimal carbon and nitrogen sources could produce 1.03 g/L of exopolysaccharides. After purification, two heteropolysaccharides (AC-EPS1 and AC-EPS2) were obtained and characterized to provide the basic structure information. As the main component of the produced EPS, AC-EPS2 (accounting for 89.63%) was mainly composed of galactose (87.42%) with Mw (molecular weight) and R.M.S. (root-mean-square) radius of 1.18 × 105 g/mol and 25.3 nm, respectively. Furthermore, the spherical and flexible chain morphologies of EPS were observed in different solvents by TEM. The structural and morphological information of purified EPS were significant for further study on their structure-activity relationship and related applications.


Assuntos
Antrodia/metabolismo , Fermentação , Polissacarídeos/química , Antrodia/química , Meios de Cultura/química , Polissacarídeos/biossíntese , Polissacarídeos/isolamento & purificação , Açúcares/química , Açúcares/metabolismo
7.
J Sci Food Agric ; 99(1): 449-456, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29900550

RESUMO

BACKGROUND: Antroquinonol, a ubiquinone derivative that shows anticancer and anti-inflammatory activities, is produced during solid-state fermentation of Antrodia camphorata; however, it cannot be biosynthesized via conventional submerged fermentation. RESULTS: A method for enhancing the biosynthesis of antroquinonol by controlling pH and adding an oxygen vector in a 7 L bioreactor was studied. In shake-flask experiments, a maximum antroquinonol production of 31.39 ± 0.78 mg L-1 was obtained by fermentation with adding 0.2 g L-1 coenzyme Q0 (CoQ0 ), at the 96th hour. Following kinetic analysis of the fermentation process, pH control strategies were investigated. A maximum antroquinonol production of 86.47 ± 3.65 mg L-1 was achieved when the pH was maintained at 5.0, which exhibited an increase of 348.03% higher than the batch without pH regulation (19.30 ± 0.88 mg L-1 ). The conversion rate of CoQ0 improved from 1.51% to 20.20%. Further research revealed that the addition of n-tetradecane could increase the production of antroquinonol to 115.62 ± 4.87 mg L-1 by increasing the dissolved oxygen in the fermentation broth. CONCLUSION: The results demonstrated that pH played an important role in antroquinonol synthesis in the presence of the effective precursor CoQ0 . It was a very effective strategy to increase the yield of antroquinonol by controlling pH and adding oxygen vector. © 2018 Society of Chemical Industry.


Assuntos
Antrodia/metabolismo , Técnicas de Cultura Celular por Lotes/métodos , Meios de Cultura/química , Oxigênio/metabolismo , Ubiquinona/análogos & derivados , Técnicas de Cultura Celular por Lotes/instrumentação , Reatores Biológicos/microbiologia , Meios de Cultura/metabolismo , Fermentação , Concentração de Íons de Hidrogênio , Oxigênio/análise , Ubiquinona/biossíntese , Ubiquinona/metabolismo
8.
Food Funct ; 9(12): 6517-6525, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30474680

RESUMO

To enhance production of Antrodia cinnamomea triterpenoids (ACTs) from mycelia in solid-state culture, α-terpineol was added to the medium as an elicitor at an optimal concentration of 0.05 mL L-1. Multi-stage solvent extraction and HPLC analysis were performed, and the compositions of ACTs-E (from culture with elicitor) and ACTs-NE (from culture without elicitor) were found to be quite different. In assays of in vitro antitumor activity, ACTs-E, in comparison with ACTs-NE, produced stronger viability reduction in several tumor cell lines and stronger apoptosis induction in HeLa in a dose-dependent manner. Several related proteins involved in the mitochondrial pathway of apoptosis (p53, Bax, caspase-3) did not show expression upregulation by ACTs-E, suggesting that apoptosis induction occurred through a p53-independent process. Further analysis revealed that ACTs-E strongly inhibited synthesis of topoisomerase I (TOP1) and tyrosyl-DNA phosphodiesterase I (TDP1), which are involved in DNA repair, at both transcriptional and protein levels. Our findings suggest that ACTs-E have potential for applications in the pharmaceutical, clinical, and functional food industries, as a novel antitumor agent and a dual TOP1/TDP1 inhibitor.


Assuntos
Antineoplásicos Fitogênicos/biossíntese , Antrodia/metabolismo , Cicloexenos/metabolismo , Monoterpenos/metabolismo , Extratos Vegetais/antagonistas & inibidores , Triterpenos/metabolismo , Antineoplásicos Fitogênicos/análise , Antineoplásicos Fitogênicos/farmacologia , Antrodia/química , Antrodia/crescimento & desenvolvimento , Apoptose/efeitos dos fármacos , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular Tumoral , Meios de Cultura/metabolismo , DNA Topoisomerases Tipo I/genética , DNA Topoisomerases Tipo I/metabolismo , Humanos , Micélio/química , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Triterpenos/análise , Triterpenos/farmacologia
9.
Int J Nanomedicine ; 13: 5059-5073, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30233173

RESUMO

Purpose: Nanoencapsulated triterpenoids from petri dish-cultured Antrodia cinnamomea (PAC) and its amelioration effects on reproductive function in diabetic rats were investigated. Materials and methods: PAC encapsulated in silica-chitosan nanoparticles (Nano-PAC) was prepared by the biosilicification method. The diabetic condition in male Sprague Dawley rats was induced by high-fat diet and streptozotocin (STZ). Three different doses of Nano-PAC (4, 8, and 20 mg/kg) were administered for 6 weeks. Metformin and control of nanoparticles (Nano-con) were taken as positive and negative controls, respectively. Results: The average particle size was ~79.46±1.63 nm, and encapsulation efficiency was ~73.35%±0.09%. Nano-PAC administration improved hyperglycemia and insulin resistance. In addition, Nano-PAC ameliorated the morphology of testicular seminiferous tubules, sperm morphology, motility, ROS production, and mitochondrial membrane potential. Superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) antioxidant, as well as testosterone, luteinizing hormone (LH), and follicle stimulating hormone (FSH) were increased, whereas proinflammatory cytokines TNF-α, IL-6, and IFN-γ were decreased. Conclusion: In the present study, we successfully nanoencapsulated PAC and found that a very low dosage of Nano-PAC exhibited amelioration effects on the reproductive function of diabetic rats.


Assuntos
Antrodia/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Genitália Masculina/efeitos dos fármacos , Hiperglicemia/prevenção & controle , Nanopartículas/administração & dosagem , Triterpenos/isolamento & purificação , Triterpenos/farmacologia , Animais , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Nanopartículas/química , Ratos , Ratos Sprague-Dawley , Triterpenos/química
10.
Food Chem Toxicol ; 119: 380-386, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29475041

RESUMO

Esophageal cancer is associated with a high mortality rate and easy metastasis. The aim of this study is to investigate the effect of the bio-product Antrodia cinnamomea mycelial fermentation broth (AC-MFB) on the epithelial mesenchymal transition (EMT) of human esophageal cancer cells and the molecular mechanisms underlying these effects. Transforming growth factor ß (TGF-ß) was used to induce EMT in human esophageal BE3 cancer cells. Changes in cell morphology and migration potential were examined. The expression of E-cadherin, N-cadherin, vimentin, and other transcriptional factors was studied by western blot assay. The results showed that AC-MFB was not only able to upregulate the expression of Ecadherin and attenuate the TGF-ß-induced overexpression of vimentin and N-cadherin, but it also reversed the TGF-ß-induced changes in cell morphology from polygonal to spindle-shaped and delayed the migration potential of BE3 cells. Furthermore, AC-MFB treatment was able to inhibit the expression levels of both Twist and Twist1. Overall, AC-MFB was able to inhibit the EMT of esophageal cancer BE3 cells, which was accompanied by Twist and Twist1 downregulation.


Assuntos
Adenocarcinoma/patologia , Antrodia/metabolismo , Produtos Biológicos/farmacologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Neoplasias Esofágicas/patologia , Fermentação , Micélio/metabolismo , Adenocarcinoma/metabolismo , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Meios de Cultura , Regulação para Baixo , Neoplasias Esofágicas/metabolismo , Humanos , Proteínas Nucleares/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/fisiologia , Proteína 1 Relacionada a Twist/metabolismo , Vimentina/metabolismo
11.
J Agric Food Chem ; 65(48): 10395-10405, 2017 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-29125753

RESUMO

In recent years, Antrodia cinnamomea has attracted great attention around the world as an extremely precious edible and medicinal mushroom. Ubiquinone derivatives, which are characteristic metabolites of A. cinnamomea, have shown great bioactivities. Some of them have been regarded as promising therapeutic agents and approved into clinical trial by the U.S. Food and Drug Administration. Although some excellent reviews have been published covering different aspects of A. cinnamomea, this review brings, for the first time, complete information about the structure, bioactivity, chemical synthesis, biosynthesis, and metabolic regulation of ubiquinone derivatives in A. cinnamomea. It not only advances our knowledge on the bioactive metabolites, especially the ubiquinone derivatives, in A. cinnamomea but also provides valuable information for the investigation on other edible and medicinal mushrooms.


Assuntos
Antrodia/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ubiquinona/química , Ubiquinona/farmacologia , Verduras/química , Animais , Antrodia/metabolismo , Humanos , Extratos Vegetais/metabolismo , Ubiquinona/metabolismo , Verduras/metabolismo
12.
Proteomics ; 17(17-18)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28792668

RESUMO

Medicinal mushroom Antrodia camphorata sporulate large numbers of arthroconidia in submerged fermentation, which is rarely reported in basidiomycetous fungi. Nevertheless, the molecular mechanisms underlying this asexual sporulation (conidiation) remain unclear. Here, we used comparative transcriptomic and proteomic approaches to elucidate possible signaling pathway relating to the asexual sporulation of A. camphorata. First, 104 differentially expressed proteins and 2586 differential cDNA sequences during the culture process of A. camphorata were identified by 2DE and RNA-seq, respectively. By applying bioinformatics analysis, a total of 67 genes which might play roles in the sporulation were obtained, and 18 of these genes, including fluG, sfgA, SfaD, flbA, flbB, flbC, flbD, nsdD, brlA, abaA, wetA, ganB, fadA, PkaA, veA, velB, vosA, and stuA might be involved in a potential FluG-mediated signaling pathway. Furthermore, the mRNA expression levels of the 18 genes in the proposed FluG-mediated signaling pathway were analyzed by quantitative real-time PCR. In summary, our study helps elucidate the molecular mechanisms underlying the asexual sporulation of A. camphorata, and provides also useful transcripts and proteome for further bioinformatics study of this valuable medicinal mushroom.


Assuntos
Antrodia/crescimento & desenvolvimento , Antrodia/metabolismo , Proteínas Fúngicas/metabolismo , Proteoma/metabolismo , Transdução de Sinais , Esporos Fúngicos/metabolismo , Antrodia/genética , Regulação Fúngica da Expressão Gênica , Proteômica/métodos , Reprodução Assexuada , Transcriptoma
13.
Appl Microbiol Biotechnol ; 101(11): 4701-4711, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28255687

RESUMO

Antrodia cinnamomea, an endemic basidiomycete used as a health food in Taiwan, is known to synthesize antroquinonols, which were reported to have notable medicinal potential in oncology and immunology. However, the biosynthetic pathway of these compounds is currently unclear. Our previous study showed that a pks63787 knockout mutant of A. cinnamomea (∆pks63787) is deficient in the biosynthesis of several aromatic metabolites. In this study, we pointed by phylogenetic analysis that pks63787 likely encodes an orsellinic acid synthase. Moreover, amendment of the cultural medium with orsellinic acid not only restores the ability of ∆pks63787 to produce its major pigment and other deficient metabolites, e.g., antroquinonols, but also enhances the productivity of several antroquinonols, including two new compounds 2 and 3. These results provide direct evidence that the PKS63787 is involved in the biosynthesis of antroquinonols and confirmed our hypothesis that the 6-methylcyclohexenone moiety was synthesized via the PKS63787-mediated polyketide pathway. In conclusion, PKS63787 might function as orsellinic acid synthase and orsellinic acid is an important precursor indispensable for the biosynthesis of the major pigment and antroquinonols in A. cinnamomea. To facilitate further basic or applied study, a putative biosynthesis pathway map of antroquinonols is proposed.


Assuntos
Antrodia/enzimologia , Vias Biossintéticas/genética , Policetídeo Sintases/metabolismo , Resorcinóis/metabolismo , Ubiquinona/análogos & derivados , Antrodia/genética , Antrodia/metabolismo , Produtos Biológicos/metabolismo , Carpóforos , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Técnicas de Inativação de Genes , Estrutura Molecular , Mutação , Filogenia , Policetídeo Sintases/genética , Taiwan , Ubiquinona/biossíntese , Ubiquinona/química
14.
Oxid Med Cell Longev ; 2017: 7841823, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28337253

RESUMO

In the present study, the components of A. cinnamomea (AC) mycelia were systematically analyzed. Subsequently, its hepatoprotective effects and the underlying mechanisms were explored using a mouse model of acute alcohol-induced liver injury. AC contained 25 types of fatty acid, 16 types of amino acid, 3 types of nucleotide, and 8 types of mineral. The hepatoprotective effects were observed after 2 weeks of AC treatment at doses of 75 mg/kg, 225 mg/kg, and 675 mg/kg in the mouse model. These effects were indicated by the changes in the levels of aspartate aminotransferase, alanine aminotransferase, several oxidation-related factors, and inflammatory cytokines in serum and/or liver samples. AC reduced the incidence rate of necrosis, inflammatory infiltration, fatty droplets formation, and cell apoptosis in liver detecting via histological and TUNEL assay. In addition, AC reduced the expression of cleaved caspase-3, -8, and -9 and the levels of phosphor-protein kinase B (Akt) and phosphor-nuclear factor-κB (NF-κB) in the liver samples. Collectively, AC-mediated hepatoprotective effects in a mouse model of acute alcohol-induced liver injury are the result of reduction in oxidative stress. This may be associated with Akt/NF-κB signaling. These results provide valuable evidence to support the use of A. cinnamomea as a functional food and/or medicine.


Assuntos
Antrodia/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Alanina Transaminase/sangue , Álcoois/toxicidade , Animais , Antioxidantes/metabolismo , Antrodia/metabolismo , Aspartato Aminotransferases/sangue , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Fígado/metabolismo , Fígado/patologia , Camundongos , NF-kappa B/metabolismo , Extratos Vegetais/química , Substâncias Protetoras/química , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo
15.
J Agric Food Chem ; 65(9): 1874-1886, 2017 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-28234464

RESUMO

Antodia cinnamomea, a precious brown-rot fungus endemic to Taiwan, has pharmaceutical applications due to its diverse array of metabolites. The terpenoids found in A. cinnamomea contribute to its most important bioactivities. We identified several terpenoid compounds in A. cinnamomea and revealed that their content in mycelium and fruiting body were significantly different. Using next-generation sequencing and an in-house transcriptome database, we identified several terpene synthase (TPS) candidates. After sequence analysis and functional characterization, 10 out of 12 candidates were found to have single or multiple terpene synthesis functions. Most of the terpenoid compounds were found to confer important bioactivities. RT-PCR results showed a positive correlation between terpene synthase expression pattern and terpenoid content. In addition, we identified several modification enzyme candidates that may be involved in the postmodification of terpenoid compounds with a genomic DNA scaffold, and a putative genetic network.


Assuntos
Antrodia/metabolismo , Carpóforos/metabolismo , Redes Reguladoras de Genes , Micélio/genética , Terpenos/metabolismo , Antrodia/genética , Antrodia/crescimento & desenvolvimento , Carpóforos/genética , Carpóforos/crescimento & desenvolvimento , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Transcriptoma
16.
J Sci Food Agric ; 97(2): 595-599, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27098319

RESUMO

BACKGROUND: Antroquinonol have significantly anti-tumour effects on various cancer cells. There is still lack of reports on regulation of environmental factors on antroquinonol production by Antrodia camphorata. RESULTS: An effective submerged fermentation method was employed to induce antroquinonol with adding H2 O2 . The production of antroquinonol was 57.81 mg L-1 after fermentation for 10 days when adding 25 mmol L-1 H2 O2 at day 4 of the fermentation process. Then, antroquinonol was further increased to 80.10 mg L-1 with cell productivity of 14.94 mg g-1 dry mycelium when the feeding rate of H2 O2 was adjusted to 0.2 mmol L-1 h-1 in the 7 L fermentation bioreactor. After inhibiting the generation of reactive oxygen species with the inhibitor diphenyleneiodoium, the synthesis of antroquinonol from A. camphorata was significantly reduced, and the yield was only 3.3 mg L-1 . CONCLUSION: The results demonstrated that addition of H2 O2 was a very effective strategy to induce and regulate the synthesis of antroquinonol in submerged fermentation. Reactive oxygen species generated by H2 O2 during fermentation caused oxidative stress, which induced the synthesis of antroquinonol and other chemical compounds. Moreover, it is very beneficial process to improve production and diversity of the active compounds during liquid fermentation of A. camphorata mycelium. © 2016 Society of Chemical Industry.


Assuntos
Antineoplásicos/metabolismo , Antrodia/efeitos dos fármacos , Peróxido de Hidrogênio/farmacologia , Oxidantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Ubiquinona/análogos & derivados , Antineoplásicos/análise , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Antrodia/química , Antrodia/crescimento & desenvolvimento , Antrodia/metabolismo , Reatores Biológicos , China , Inibidores Enzimáticos/farmacologia , Fermentação/efeitos dos fármacos , Estrutura Molecular , Micélio/química , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Micologia/métodos , Oniocompostos/farmacologia , Concentração Osmolar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Estereoisomerismo , Fatores de Tempo , Ubiquinona/análise , Ubiquinona/biossíntese , Ubiquinona/química , Ubiquinona/isolamento & purificação
17.
J Agric Food Chem ; 65(1): 74-86, 2017 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-28001060

RESUMO

Antroquinonol (AQ) and 4-acetylantroquinonol B (4-AAQB), isolated from the mycelium of Antrodia cinnamomea, have a similar chemical backbone to coenzyme Q (CoQ). Based on the postulation that biosynthesis of both AQ and 4-AAQB in A. cinnamomea starts from the polyketide pathway, we cultivated this fungus in a culture medium containing [U-13C]oleic acid, and then we analyzed the crude extracts of the mycelium using UHPLC-MS. We found that AQ and 4-AAQB follow similar biosynthetic sequences as CoQ. Obvious [13C2] fragments on the ring backbone were detected in the mass spectrum for [13C2]AQ, [13C2]4-AAQB, and their [13C2] intermediates found in this study. The orsellinic acid, formed from acetyl-CoA and malonyl-CoA via the polyketide pathway, was found to be a novel benzoquinone ring precursor for AQ and 4-AAQB. The identification of endogenously synthesized farnesylated intermediates allows us to postulate the routes of AQ and 4-AAQB biosynthesis in A. cinnamomea.


Assuntos
4-Butirolactona/análogos & derivados , Antrodia/metabolismo , Policetídeos/metabolismo , Resorcinóis/metabolismo , Ubiquinona/análogos & derivados , 4-Butirolactona/biossíntese , 4-Butirolactona/química , Antrodia/química , Vias Biossintéticas , Cicloexanonas/química , Proteínas Fúngicas/metabolismo , Estrutura Molecular , Micélio/química , Micélio/metabolismo , Ubiquinona/biossíntese , Ubiquinona/química
18.
Oncotarget ; 7(39): 62836-62861, 2016 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-27542238

RESUMO

The present study revealed the anti-aging properties of antcin M (ANM) and elucidated the molecular mechanism underlying the effects. We found that exposure of human normal dermal fibroblasts (HNDFs) to high-glucose (HG, 30 mM) for 3 days, accelerated G0/G1 phase arrest and senescence. Indeed, co-treatment with ANM (10 µM) significantly attenuated HG-induced growth arrest and promoted cell proliferation. Further molecular analysis revealed that ANM blocked the HG-induced reduction in G1-S transition regulatory proteins such as cyclin D, cyclin E, CDK4, CDK6, CDK2 and protein retinoblastoma (pRb). In addition, treatment with ANM eliminated HG-induced reactive oxygen species (ROS) through the induction of anti-oxidant genes, HO-1 and NQO-1 via transcriptional activation of Nrf2. Moreover, treatment with ANM abolished HG-induced SIPS as evidenced by reduced senescence-associated ß-galactosidase (SA-ß-gal) activity. This effect was further confirmed by reduction in senescence-associated marker proteins including, p21CIP1, p16INK4A, and p53/FoxO1 acetylation. Also, the HG-induced decline in aging-related marker protein SMP30 was rescued by ANM. Furthermore, treatment with ANM increased SIRT-1 expression, and prevented SIRT-1 depletion. This protection was consistent with inhibition of SIRT-1 phosphorylation at Ser47 followed by blocking its upstream kinases, p38 MAPK and JNK/SAPK. Further analysis revealed that ANM partially protected HG-induced senescence in SIRT-1 silenced cells. A similar effect was also observed in Nrf2 silenced cells. However, a complete loss of protection was observed in both Nrf2 and SIRT-1 knockdown cells suggesting that both induction of Nrf2-mediated anti-oxidant defense and SIRT-1-mediated deacetylation activity contribute to the anti-aging properties of ANM in vitro. Result of in vivo studies shows that ANM-treated C. elegens exhibits an increased survival rate during HG-induced oxidative stress insult. Furthermore, ANM significantly extended the life span of C. elegans. Taken together, our results suggest the potential application of ANM in age-related diseases or as a preventive reagent against aging process.


Assuntos
Senescência Celular , Fibroblastos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Compostos Fitoquímicos/farmacologia , Sirtuína 1/metabolismo , Pele/citologia , Triterpenos/farmacologia , Acetilcisteína/farmacologia , Antioxidantes/metabolismo , Antrodia/metabolismo , Apoptose , Ciclo Celular , Proliferação de Células , Sobrevivência Celular , Colestenonas/farmacologia , Células Endoteliais/metabolismo , Inativação Gênica , Glucose/química , Humanos , Hiperglicemia/metabolismo , Medicina Tradicional Chinesa , Estresse Oxidativo , Fosforilação , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Proteína do Retinoblastoma/metabolismo , Estilbenos/farmacologia
19.
PLoS One ; 11(4): e0153087, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27046059

RESUMO

Antrodia cinnamomea (A. cinnamomea) is an indigenous medical fungus in Taiwan and has multiple biological functions, including hepatoprotective and immune-modulatory effects. Currently, the commercially available A. cinnamomea are mainly liquid- and solid-state fermented A. cinnamomea. However, the hepatoprotective effect of solid-state fermented A. cinnamomea has never been reported. Here we evaluate the ability of air-dried, ground and non-extracted wheat-based solid-state fermented A. cinnamomea (WFAC) to protect against carbon tetrachloride (CCl4)-induced hepatic injury in vivo. The results showed that oral administration of WFAC dose dependently (180, 540 and 1080 mg/kg) ameliorated the increase in plasma aspartate aminotransferase and alanine aminotransferase levels caused by chronic repeated CCl4 intoxication in rats. WFAC significantly reduced the CCl4-induced increase in hepatic lipid peroxidation levels and hydroxyproline contents, as well as reducing the spleen weight and water content of the liver. WFAC also restored the hepatic soluble protein synthesis and plasma albumin concentration in CCl4-intoxicated rats, but it did not affect the activities of superoxide dismutase, catalase, or glutathione peroxidase. In addition, a hepatic morphological analysis showed that the hepatic fibrosis and necrosis induced by CCl4 were significantly ameliorated by WFAC. Furthermore, the body weights of control rats and WFAC-administered rats were not significantly different, and no adverse effects were observed in WFAC-administered rats. These results indicate that WFAC is a nontoxic hepatoprotective agent against chronic CCl4-induced hepatic injury.


Assuntos
Antrodia/metabolismo , Intoxicação por Tetracloreto de Carbono/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fermentação , Triticum , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Masculino , Ratos , Ratos Wistar
20.
J Sci Food Agric ; 96(14): 4690-4701, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26919329

RESUMO

BACKGROUND: Antrodia camphorata is proven to probably inhibit the neurotoxicity of amyloid ß-peptide (Aß), known as a risk factor toward the development of Alzheimer's disease. Deep ocean water (DOW), drawn from an ocean depth of more than 200 m, has proven to stimulate the growth and metabolite biosynthesis of fungi owing to its rich minerals and trace elements. Based on these advantages of DOW, this study used statistical response surface methodology (RSM) to investigate the effects of DOW on the growth and anti-Aß-induced neurocytotoxicity ability of A. camphorata. RESULTS: The results showed that DOW was useful for increasing the biomass of A. camphorata and enhancing its neuroprotective capability. The anti-Aß40-induced neurocytotoxicity ability of filtrate was increased via raising the mycelium-secreted components. Furthermore, the anti-Aß40-induced neurocytotoxicity ability of mycelium was also increased by the DOW-stimulated intracellular antioxidants. Using 80% DOW concentration, initial pH 3.3 and 20% inoculum size as the optimal culture conditions of A. camphorata significantly stimulated the biomass and mycelium-mediated Aß40-induced cell viability from 302 ± 14 mg per 100 mL and 49.2 ± 2.2% to 452 ± 33 mg per 100 mL and 65.0 ± 7.4% respectively. CONCLUSION: This study indicated that DOW could be used as a promising supplementary for the production of A. camphorata secondary metabolites with strong antioxidant activity to protect neuron cells from damage based on Aß stimulation cytotoxicity. © 2016 Society of Chemical Industry.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Antrodia/metabolismo , Meios de Cultura , Neurônios/efeitos dos fármacos , Água do Mar , Animais , Biomassa , Fermentação , Oceanos e Mares , Células PC12 , Ratos
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