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1.
Cancer Immunol Immunother ; 73(1): 18, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38240856

RESUMO

Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor worldwide. Within HCC's tumor microenvironment, focal adhesion kinase (FAK) plays a critical role. Regulatory T cells (Treg) modulate the polarization of tumor-associated macrophages , but the relationship between FAK, Treg cells, and macrophages remains underexplored. Phellinus linteus (PL) shows promise as a treatment for HCC due to its pharmacological effects. This study aimed to explore the relationship between FAK and Treg-macrophages and to assess whether PL could exert a protective effect through the FAK process in HCC. Initially, C57BL/6-FAK-/- tumor-bearing mice were utilized to demonstrate that FAK stimulates HCC tumor development. High dosages (200 µM) of FAK and the FAK activator ZINC40099027 led to an increase in Treg (CD4+CD25+) cells, a decrease in M1 macrophages (F4/80+CD16/32+, IL-12, IL-2, iNOS), and an increase in M2 macrophages (F4/80+CD206+, IL-4, IL-10, Arg1, TGF-ß1). Additionally, FAK was found to encourage cell proliferation, migration, invasion, and epithelial-mesenchymal transition while inhibiting apoptosis in HepG2 and SMMC7721 cells. These effects were mediated by the PI3K/AKT1/Janus Kinase (JAK)/ signal transducer and activator of transcription 3 (STAT3), and mitogen-activated protein kinase (p38 MAPK)/Jun N-terminal Kinase (JNK) signaling pathways. Furthermore, PL exhibited a potent antitumor effect in vivo in a dose-dependent manner, reducing FAK, Treg cells, and M2 macrophages, while increasing M1 macrophages. This effect was achieved through the inhibition of the PI3K/AKT/JAK/STAT3, and p38/JNK pathways. Overall, our findings suggest that FAK promotes HCC via Treg cells that polarize macrophages toward the M2 type through specific signaling pathways. PL, acting through FAK, could be a protective therapy against HCC.


Assuntos
Basidiomycota , Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Linfócitos T Reguladores/metabolismo , Neoplasias Hepáticas/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Linhagem Celular Tumoral , Microambiente Tumoral
2.
Int J Mol Sci ; 24(4)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36835095

RESUMO

The prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated to be approximately about 25.24% of the population worldwide. NAFLD is a complex syndrome and is characterized by a simple benign hepatocyte steatosis to more severe steatohepatitis in the liver pathology. Phellinus linteus (PL) is traditionally used as a hepatoprotective supplement. Styrylpyrone-enriched extract (SPEE) obtained from the PL mycelia has been shown to have potential inhibition effects on high-fat- and high-fructose-diet-induced NAFLD. In the continuous study, we aimed to explore the inhibitory effects of SPEE on free fatty acid mixture O/P [oleic acid (OA): palmitic acid (PA); 2:1, molar ratio]-induced lipid accumulation in HepG2 cells. Results showed that SPEE presented the highest free radical scavenging ability on DPPH and ABTS, and reducing power on ferric ions, better than that of partitions obtained from n-hexane, n-butanol and distilled water. In free-fatty-acid-induced lipid accumulation in HepG2 cells, SPEE showed an inhibition effect on O/P-induced lipid accumulation of 27% at a dosage of 500 µg/mL. As compared to the O/P induction group, the antioxidant activities of superoxide dismutase, glutathione peroxidase and catalase were enhanced by 73%, 67% and 35%, respectively, in the SPEE group. In addition, the inflammatory factors (TNF-α, IL-6 and IL-1ß) were significantly down-regulated by the SPEE treatment. The expressions of anti-adipogenic genes involved in hepatic lipid metabolism of 5' adenosine monophosphate (AMP)-activated protein kinase (AMPK), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) were enhanced in the SPEE supplemented HepG2 cells. In the protein expression study, p-AMPK, SIRT1 and PGC1-α were significantly increased to 121, 72 and 62%, respectively, after the treatment of SPEE. Conclusively, the styrylpyrone-enriched extract SPEE can ameliorate lipid accumulation and decrease inflammation and oxidative stress through the activation of SIRT1/AMPK/PGC1-α pathways.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Phellinus , Humanos , Proteínas Quinases Ativadas por AMP/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Células Hep G2/efeitos dos fármacos , Células Hep G2/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Sirtuína 1/metabolismo , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Pironas/química , Pironas/farmacologia , Phellinus/química
3.
Molecules ; 28(13)2023 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-37446762

RESUMO

We optimized an ultrasound-assisted extraction process of Phellinus linteus mycelium polysaccharides (PLPs) and studied their monosaccharide composition and bacteriostatic properties. Based on a single-factor experiment, a three-factor, three-level Box-Behnken design was used to optimize the ultrasound-assisted extraction process of PLP, using the yield of PLP as the index. The chemical composition and monosaccharide composition of PLP were determined by chemical analysis and HPLC analysis, respectively. Microscopic morphological analysis of the surface of PLP was performed via swept-surface electron microscopy. The bacteriostatic properties of PLP were determined using the spectrophotometric turbidimetric method. The results showed that the best extraction process of PLP with ultrasonic assistance achieved a result of 1:42 g/mL. In this method, the ultrasonic temperature was 60 °C, ultrasonic extraction was performed for 20 min, and the yield of PLP was 12.98%. The monosaccharide composition of PLP mainly contains glucose (Glc), mannose (Man), galactose (Gal), and glucuronic acid (GlcA). The intracellular polysaccharide of Phellinus igniarius Mycelia (PIP) is an irregular spherical accumulation, the surface is rough and not smooth, and the extracellular polysaccharide (PEP) is a crumbly accumulation. PIP has a stronger inhibitory ability for S. aureus and E. coli and a slightly weaker inhibitory effect for B. subtilis; the inhibitory effect of PEP on S. aureus, E. coli, and B. subtilis is slightly inferior to that of PIP.


Assuntos
Escherichia coli , Staphylococcus aureus , Humanos , Polissacarídeos/farmacologia , Polissacarídeos/química , Monossacarídeos
4.
Mol Biol Rep ; 49(4): 2785-2793, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35079934

RESUMO

BACKGROUND: Thyroid carcinoma (TC) is the most common malignant tumor of the endocrine system. Phellinus linteus polysaccharide (PLP) physiologically acts as a suitable anti-tumor molecule. In this study, for the first time, we systematically investigated the anti-tumor activity of PLP in TC, aiming to promote the application of PLP in TC treatment. METHODS AND RESULTS: TPC-1 and SW579 cells were treated with or without PLP. After treatment, MTT and EdU proliferation assays were performed to detect cell growth. Cell cycle was analyzed using flow cytometry. JC-1 staining was used to track change of mitochondrial membrane potential (MMP). Apoptotic cells were stained with annexin V-fluorescein isothiocyanate/propidium iodide and subsequently analyzed using flow cytometry. mCherry-GFP-LC3 was overexpressed in TC cells by lentiviral technology and the autophagosome was observed using confocal laser scanning microscope. Transwell migration and Matrigel invasion assays were performed to elucidate cell metastasis. Finally, underlying molecular mechanisms were investigated using RT-qPCR and western blotting. PLP inhibited cell growth in TC cells, which was attributable to the PLP-induced arrest at G0/G1 phase of cell cycle. PLP decreased the MMP, induced cell apoptosis, and promoted mitochondrial autophagy and endoplasmic reticulum autophagy. Furthermore, PLP may promote cell apoptosis via nuclear factor kappa-B pathway. In addition, PLP also inhibited cell migration and invasion through modulating the expression of epithelial-mesenchymal transition molecules such as E-cadherin, N-cadherin, and Vimentin CONCLUSIONS: PLP exhibits notable anti-tumor activity in TC cells and may be used in TC treatment.


Assuntos
Basidiomycota , Neoplasias da Glândula Tireoide , Apoptose , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Polissacarídeos/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/metabolismo
5.
Prep Biochem Biotechnol ; 52(1): 89-98, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33939578

RESUMO

In this study, Phellinus linteus polysaccharides (PLPS) and proteins were simultaneously separated from P. linteus mycelia by using an aqueous two-phase system (ATPS) based on choline chloride ([Chol]Cl)/K2HPO4, and the physicochemical and antioxidant properties of PLPS after ATPS extraction were evaluated. Results demonstrated that the maximal extraction efficiencies of 68.53% ± 0.29% PLPS and 82.37% ± 0.41% proteins were obtained when the cholinium-based ATPS contained 68.9% K2HPO4, 20% [Chol]Cl, 10.0 mg mL-1 crude water extract (1.0 mL), and distilled water (4.0 mL) at shaking time and temperature of 30 min and 21.2 °C, respectively. Compared with C-PLPS obtained using traditional ethanol precipitation and isolation protocols, PLPS had higher carbohydrate content (63.58% ± 1.12%), lower molecular weight (15.2 kDa, 80%), different monosaccharide compositions, and showed similar preliminary structural characterizations. Moreover, PLPS exhibited more evident scavenging effects on free radicals and in vitro antioxidant activities than C-PLPS. Therefore, the method of [Chol]Cl/K2HPO4 ATPS can be developed as an effective strategy for the separation/purification of highly bioactive polysaccharides.


Assuntos
Antioxidantes/isolamento & purificação , Basidiomycota/química , Polissacarídeos/isolamento & purificação , Antioxidantes/farmacologia , Transição de Fase , Polissacarídeos/farmacologia , Água/química
6.
Curr Issues Mol Biol ; 43(1): 365-383, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34203617

RESUMO

Although the individual consumption of medicinal mushrooms, including Phellinus linteus (PL), Ganoderma lucidum (GL), and Inonotus obliquus (IO), is known to be neuroprotective, the associated mechanisms underlying their therapeutic synergism on focal cerebral ischemia (fCI) have yet to be elucidated. This study aimed to demonstrate the neuroprotective effects of mixed mushroom mycelia (MMM) against experimental fCI. The water-fractions, ethanolic-fractions, and ethyl acetate-fractions of the MMM (PL, GL, and IO) grown in a barley medium using solid-state fermentation techniques were prepared and their protective effects against glutamate-induced excitotoxicity were compared in PC-12 cells. After the identification of the water extracts of MMM (wMMM) as the most suitable form, which possessed the lowest toxicity and highest efficacy, further analyses for evaluating the anti-apoptotic effects of wMMM, including Hoechst 33258-based nuclear staining, fluorescence-activated cell sorting, and reactive oxygen species (ROS) detection assays, were performed. Rats were subjected to a 90 min middle cerebral artery occlusion and reperfusion, after which a wMMM treatment resulted in significant dose-dependent improvements across a number of parameters. Furthermore, measurements of intracellular ROS and levels of antioxidant enzymes revealed a wMMM-mediated ROS attenuation and antioxidant enzyme upregulation. We suggest that wMMM is neuroprotective against fCI through its anti-apoptotic and anti-oxidative effects.


Assuntos
Agaricales/química , Isquemia Encefálica/prevenção & controle , Hordeum/química , Micélio/química , Fármacos Neuroprotetores/farmacologia , Água/química , Agaricales/crescimento & desenvolvimento , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Meios de Cultura/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Micélio/efeitos dos fármacos , Micélio/crescimento & desenvolvimento , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
7.
FASEB J ; 34(1): 1065-1078, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31914668

RESUMO

The hypoglycemic effect of Phellinus linteus polysaccharide extract (PLPE) has been documented in several previous studies, but the functional interactions among PLPE, gut microbiota, and the hypoglycemic effect remain unclear. We examined the regulatory effect of PLPE on gut microbiota, and the molecular mechanism underlying improvement of insulin resistance, using a type 2 diabetic rat model. Here, 24 male Sprague-Dawley rats were randomly divided into four groups that were subjected to intervention of saline (normal and model control group), metformin (120 mg/kg.bw), and PLPE (600 mg/kg.bw) by oral administration. After 8 weeks of treatment, PLPE increased levels of short-chain fatty acids (SCFAs) by enhancing abundance of SCFA-producing bacteria. SCFAs maintained intestinal barrier function and reduced lipopolysaccharides content in blood, thereby helping to reduce systemic inflammation and reverse insulin resistance. Our findings suggest that PLPE (in which polysaccharides are the major component) has potential application as a prebiotic for regulating gut microbiota composition in diabetic patients.


Assuntos
Regulação da Expressão Gênica , Resistência à Insulina , Extratos Vegetais/farmacologia , Polissacarídeos/farmacologia , Animais , Proteínas de Transporte/metabolismo , Ácidos Graxos Voláteis/sangue , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Hipoglicemiantes/farmacologia , Insulina/metabolismo , Interleucina-6/metabolismo , Lipopolissacarídeos/sangue , Masculino , Phellinus , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
8.
Molecules ; 26(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34361649

RESUMO

Hispolon, a polyphenol compound isolated from Phellinus linteus, has been reported to exhibit antioxidant, antiproliferative, and antitumor activities. This study aimed to explore the antitumor effects of hispolon on glioblastoma multiforme (GBM) cells in vitro and in vivo. The results revealed that hispolon significantly inhibited GBM cell proliferation and induced apoptosis through caspase-9 and caspase-3 activation and PARP cleavage. Hispolon also induced cell cycle G2/M phase arrest in GBM cells, as supported by flow cytometry analysis and confirmed by a decrease in cyclin B1, cdc2, and cdc25c protein expressions in a dose- and time-dependent manner. Furthermore, hispolon suppressed the migration and invasion of GBM cells by modulating epithelial-mesenchymal transition (EMT) markers via wound healing, transwell assays, and real-time PCR. Moreover, hispolon significantly reduced tumor growth in DBTRG xenograft mice and activated caspase-3 in hispolon-treated tumors. Thus, our findings revealed that hispolon is a potential candidate for the treatment of GBM.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Catecóis/farmacologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Glioblastoma/tratamento farmacológico , Animais , Basidiomycota/metabolismo , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Ratos
9.
Environ Res ; 190: 110017, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32768475

RESUMO

Nature as an infinite treasure of chemotypes and pharmacophores will continue to play an imperative role in the drug discovery. Natural products (NPs) such as plant and fungal metabolites have emerged as leads in drug discovery during recent years due to their efficacy, safety and selectivity. The current review summarizes natural sources as well as pharmacological potential of hispolon which is a major constituent of traditional medicinal mushroom Phellinus linteus. The study aims to update the scientific community about recent developments of hispolon in the arena of natural drugs by providing insights into its present status in therapeutic pursuits. Hispolon, a polyphenol has been reported to possess anticancer, antidiabetic, antioxidant, antiviral and anti-inflammatory activities. It fights against cancer via induction of apoptosis, halting cell cycle and inhibition of metastasis by targeting various cellular signaling pathways including PI3K/Akt, MAPK and NF-κB. The current review proposes that hispolon provides a novel opportunity for pharmacological applications and its styrylpyrone carbon skeleton might serve as an attractive scaffold for drug development. However, future researches are recommended to assess bioavailability, toxicological limits, pharmacokinetic and pharmacodynamic profiles of hispolon, in order to establish its potential as a potent multi-targeted drug in the near future.


Assuntos
Neoplasias , Polifenóis , Catecóis , Humanos , Fosfatidilinositol 3-Quinases , Polifenóis/farmacologia
10.
Int J Mol Sci ; 21(22)2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33266494

RESUMO

Colorectal cancer (CRC) is the fourth leading cause of cancer mortality worldwide. Aberrant activation of WNT/ß-catenin signaling present in the vast majority of CRC cases is indispensable for CRC initiation and progression, and thus is a promising target for CRC therapeutics. Hispolon is a fungal-derived polyphenol with a pronounced anticancer effect. Several hispolon derivatives, including dehydroxyhispolon methyl ether (DHME), have been chemically synthesized for developing lead molecules with stronger anticancer activity. Herein, a DHME-elicited anti-CRC effect with the underlying mechanism is reported for the first time. Specifically, DHME was found to be more cytotoxic than hispolon against a panel of human CRC cell lines, while exerting limited toxicity to normal human colon cell line CCD 841 CoN. Additionally, the cytotoxic effect of DHME appeared to rely on inducing apoptosis. This notion was evidenced by DHME-elicited upregulation of poly (ADP-ribose) polymerase (PARP) cleavage and a cell population positively stained by annexin V, alongside the downregulation of antiapoptotic B-cell lymphoma 2 (BCL-2), whereas the blockade of apoptosis by the pan-caspase inhibitor z-VAD-fmk attenuated DHME-induced cytotoxicity. Further mechanistic inquiry revealed the inhibitory action of DHME on ß-catenin-mediated, T-cell factor (TCF)-dependent transcription activity, suggesting that DHME thwarted the aberrantly active WNT/ß-catenin signaling in CRC cells. Notably, ectopic expression of a dominant-active ß-catenin mutant (∆N90-ß-catenin) abolished DHME-induced apoptosis while also restoring BCL-2 expression. Collectively, we identified DHME as a selective proapoptotic agent against CRC cells, exerting more potent cytotoxicity than hispolon, and provoking CRC cell apoptosis via suppression of the WNT/ß-catenin signaling axis.


Assuntos
Apoptose , Neoplasias Colorretais/tratamento farmacológico , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/farmacologia , Basidiomycota/química , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/fisiopatologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Humanos , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/genética
11.
Molecules ; 25(14)2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664327

RESUMO

Phellinus linteus is a well-known medicinal mushroom that is widely used in Asian countries. In several experimental models, Phellinus linteus extracts were reported to have various biological effects, including anti-inflammatory, anti-cancer, hepatoprotective, anti-diabetic, neuroprotective, and anti-angiogenic activity. In the present study, several bioactive compounds, including palmitic acid ethyl ester and linoleic acid, were identified in Phellinus linteus. The intermediate-conductance calcium-activated potassium channel (IKCa) plays an important role in the regulation of the vascular smooth muscle cells' (VSMCs) contraction and relaxation. The activation of the IKCa channel causes the hyperpolarization and relaxation of VSMCs. To examine whether Phellinus linteus extract causes vasodilation in the mesenteric arteries of rats, we measured the isometric tension using a wire myograph. After the arteries were pre-contracted with U46619 (a thromboxane analogue, 1 µM), Phellinus linteus extract was administered. The Phellinus linteus extract induced vasodilation in a dose-dependent manner, which was independent of the endothelium. To further investigate the mechanism, we used the non-selective K+ channel blocker tetraethylammonium (TEA). TEA significantly abolished Phellinus linteus extract-induced vasodilation. Thus, we tested three different types of K+ channel blockers: iberiotoxin (BKca channel blocker), apamin (SKca channel blocker), and charybdotoxin (IKca channel blocker). Charybdotoxin significantly inhibited Phellinus linteus extract-induced relaxation, while there was no effect from apamin and iberiotoxin. Membrane potential was measured using the voltage-sensitive dye bis-(1,3-dibutylbarbituric acid)-trimethine oxonol (DiBAC4(3)) in the primary isolated vascular smooth muscle cells (VSMCs). We found that the Phellinus linteus extract induced hyperpolarization of VSMCs, which is associated with a reduced phosphorylation level of 20 KDa myosin light chain (MLC20).


Assuntos
Basidiomycota/química , Artérias Mesentéricas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Vasodilatação/efeitos dos fármacos , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Apamina/farmacologia , Charibdotoxina/farmacologia , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Masculino , Potenciais da Membrana/efeitos dos fármacos , Artérias Mesentéricas/metabolismo , Contração Muscular/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Cadeias Leves de Miosina/metabolismo , Peptídeos/farmacologia , Phellinus , Fosforilação/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Sprague-Dawley , Tetraetilamônio/farmacologia , Vasoconstrição/efeitos dos fármacos
12.
BMC Complement Altern Med ; 19(1): 272, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31638956

RESUMO

BACKGROUND: This study aimed to investigate the effect of the Phellinus linteus (Mesima) decoction on podocyte injury in a rat model of focal and segmental glomerulosclerosis (FSGS) and evaluate the potential mechanisms. METHODS: FSGS resembling primary FSGS in humans was established in rats by uninephrectomy and the repeated injection of doxorubicin. The FSGS rats were randomly divided into the model group, low-dose group of P. linteus decoction (PLD-LD), medium-dose group of P. linteus decoction (PLD-MD), and high-dose group of P. linteus decoction (PLD-HD). Blood and urine analysis were performed after 12 weeks and the molecular indicators of renal function and the renal pathological changes were examined. RESULTS: FSGS developed within 12 weeks in the test group and showed progressive proteinuria and segmental glomerular scarring. Urinary protein, serum creatinine, urea nitrogen, triglycerides and cholesterol were significantly reduced following the 12-week intervention with P.linteus decoction, especially in the PLD-LD group. Renal nephrin and podocin were markedly increased. Moreover, the pathological damage in the renal tissue was alleviated by the PLD-LD intervention. CONCLUSION: The P. linteus decoction alleviated the podocyte injury in the FSGS rat model, thus minimizing the progression of glomerular sclerosis and improving renal function.


Assuntos
Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Podócitos/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Glomerulosclerose Segmentar e Focal/metabolismo , Glomerulosclerose Segmentar e Focal/fisiopatologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Masculino , Proteínas de Membrana/metabolismo , Phellinus , Podócitos/metabolismo , Ratos , Ratos Sprague-Dawley
13.
Molecules ; 24(10)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100959

RESUMO

Phellinus linteus is a popular medicinal mushroom that is widely used in China, Korea, Japan, and other Asian countries. P. linteus comprises various bioactive components, such as polysaccharides, triterpenoids, phenylpropanoids, and furans, and has proven to be an effective therapeutic agent in traditional Chinese medicine for the treatment and the prevention of various diseases. A number of studies have reported that P. linteus possesses many biological activities useful for pharmacological applications, including anticancer, anti-inflammatory, immunomodulatory, antioxidative, and antifungal activities, as well as antidiabetic, hepatoprotective, and neuroprotective effects. This review article briefly presents the recent progress made in understanding the bioactive components, biological activities, pharmacological applications, safety, and prospects of P. linteus, and provides helpful references and promising directions for further studies of P. linteus.


Assuntos
Agaricales/química , Basidiomycota/química , Produtos Biológicos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Produtos Biológicos/química , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Estrutura Molecular , Propanóis/química , Propanóis/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Terpenos/química , Terpenos/farmacologia
14.
Molecules ; 23(7)2018 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-30002357

RESUMO

In the dimethylnitrosamine (DMN)-induced hepatic fibrosis Wistar rat model, the mycelium extract of Phellinus linteus (PLE) (20 mg/Kg) displayed significant protection against hepatic fibrosis. The present investigation characterized eleven new ionone derivatives, phellinulins D⁻N (4⁻14), from the P. linteus mycelium extract and the relative stereochemical structures were constructed according to the spectroscopic and spectrometric analytical results. Some purified compounds were examined for their inhibitory effects on activated rat hepatic stellate cells (HSCs) and several isolates did exhibit significant protection. The results indicated that the mycelium of P. linteus could be explored as a hepatoprotective drug or healthy food candidate in the near future.


Assuntos
Basidiomycota/química , Misturas Complexas/farmacologia , Cirrose Hepática/prevenção & controle , Micélio/química , Animais , Misturas Complexas/química , Dimetilnitrosamina/toxicidade , Células Estreladas do Fígado/metabolismo , Células Estreladas do Fígado/patologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Wistar
15.
Environ Toxicol ; 32(9): 2113-2123, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28618133

RESUMO

Hispolon is a polyphenolic compound isolated from Phellinus linteus which exhibits antitumor activity. Here, we explored the effects of hispolon on human glioblastoma cells U87MG. Cell viability was examined by MTT assay. Growth was investigated by incubating cells with various concentrations of hispolon (25 and 50 µM) for 24, 48 or 72 h and daily cell count. Cell cycle and apoptosis assay were assessed by flow cytometry. Hispolon decreased cell viability in a dose- and time-dependent manner. The cell cycle distribution showed that hispolon enhanced the accumulation of the cells in G2/M phase. Hispolon decreased the expression of G1-S transition-related protein cyclin D4 but increased the expression of CDK inhibitor p21. Additionally, hispolon enhanced the expression of p53. Moreover, hispolon treatment was effective on U87MG cells in inhibiting cell viability and inducing cell apoptosis. Our results indicate that hispolon inhibits the cell viability, induces G2/M cell cycle arrest and apoptosis in glioblastoma U87MG cells, and p53 should play a role in hispolon-mediated antitumor activity.


Assuntos
Antineoplásicos/farmacologia , Catecóis/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Glioblastoma , Humanos , Proteína Supressora de Tumor p53/metabolismo
16.
Molecules ; 22(4)2017 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-28350337

RESUMO

3,4-Dihydroxybenzalactone (DBL) was isolated from Phellinus linteus (PL), which is a folk medicine possessing various physiological effects. In this study, we used highly metastatic A549 cells to investigate efficacy of DBL inhibition of cancer metastasis and possible mechanisms. The results revealed DBL inhibited migratory and invasive abilities of cancer cells at noncytotoxic concentrations. We found DBL suppressed enzymatic activities, protein expression, and RNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. Western blot results showed DBL decreased phosphoinositide 3-kinase (PI3K)/AKT, phosphorylation status of mitogen-activated protein kinases (MAPKs), and focal adhesion kinase (FAK)/paxillin, which correlated with cell migratory ability. DBL also affected epithelial to mesenchymal transition (EMT)-related biomarkers. In addition, DBL enhanced cytoprotective effects through elevated antioxidant enzymes including heme oxygenase 1 (HO-1), catalase, glutathione peroxidase (GPx), and superoxide dismutase (SOD). Moreover, DBL influenced the nuclear translocation of nuclear factor κB (NFκB), nuclear factor erythroid 2-related factor 2 (Nrf2), Snail, and Slug in A549 cells. Taken together, these results suggested that treatment with DBL may act as a potential candidate to inhibit lung cancer metastasis by inhibiting MMP-2 and -9 via affecting PI3K/AKT, MAPKs, FAK/paxillin, EMT/Snail and Slug, Nrf2/antioxidant enzymes, and NFκB signaling pathways.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Lactonas/química , Neoplasias Pulmonares/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , NF-kappa B/metabolismo , Extratos Vegetais/química , Células A549 , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Adesão Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Lactonas/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Metástase Neoplásica , Phellinus , Extratos Vegetais/farmacologia , Espécies Reativas de Oxigênio/metabolismo
17.
Int J Mol Sci ; 17(5)2016 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-27164091

RESUMO

Three new γ-ionylideneacetic acid derivatives, phellinulins A-C (1-3), were characterized from the mycelium extract of Phellinus linteus. The chemical structures were established based on the spectroscopic analysis. In addition, phellinulin A (1) was subjected to the examination of effects on activated rat hepatic stellate cells and exhibited significant inhibition of hepatic fibrosis.


Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Extratos Vegetais/química , Ácido Abscísico/análogos & derivados , Ácido Abscísico/química , Animais , Basidiomycota/química , Células Hep G2 , Humanos , Norisoprenoides/química , Norisoprenoides/farmacologia , Phellinus , Extratos Vegetais/farmacologia , Ratos
18.
J Dairy Sci ; 98(10): 6739-48, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26233453

RESUMO

The growth characteristics of Phellinus linteus mycelium were assessed and compared under solid-state fermentation (SSF) and submerged liquid fermentation (SLF) systems on whey permeate medium. Response surface methodology was used to investigate the growth rates of mycelia under various conditions of operating temperature (TO), initial pH, and substrate concentration ([S]). The optimal growth conditions of P. linteus mycelium were determined to be 26.1°C, pH 4.6, and 60.3g of lactose/L in the SSF system, and 29.0°C, pH 5.0, and 65.3g of lactose/L in the SLF system. The maximum growth rates were predicted to be 1.92 ± 0.01 mm/d in SSF and 192.1 ± 0.0mg/L per day in SLF. Random trials were conducted to experimentally validate the evaluated optimal conditions. The differences between the modeled and observed values were only 5.3% in the SSF system and 6.1% in the SLF system. Significant engineering factors differed between the fermentation techniques; TO was significant in both cultivation systems, whereas initial pH was significant in SSF but [S] was significant in SLF. Our findings can be used to guide the operation of the bioconversion process for cultivating P. linteus mycelium using whey permeate wastewater.


Assuntos
Basidiomycota/crescimento & desenvolvimento , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/análise , Basidiomycota/metabolismo , Fermentação , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Soro do Leite/química
19.
Biotechnol Biotechnol Equip ; 29(2): 395-403, 2015 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-26019658

RESUMO

The aim of this study was to facilitate gene discovery for functional genome studies and to identify simple sequence repeat (SSR) markers for molecular-assisted selection in Phellinus linteus. The transcriptome of Phellinus linteus was sequenced using а high-throughput RNA sequencing system - the Illumina Hiseq 2000. A total of 16,383,818 clean sequencing reads, 35,532 contigs and 25,811 unigenes were postulated. Based on similarity searches with known proteins, 19,350 genes (74.97% of the unigenes) were annotated. In the present research, 19,266, 10,978 and 7831 unigenes were mapped in Nr, Swiss-Prot and clusters of orthologous groups (COG) classifications, respectively. Of all unigenes, 6845 were categorized into three functional groups, namely biological process, cellular components and molecular function and 11,088 were annotated to 108 pathways by searching the Kyoto Encyclopedia of Genes and Genomes pathway database. A total of 1129 SSRs were identified in these unigenes. In addition, 23 candidate genes, potentially involved in sterol biosynthesis, were identified and were worthy of further investigation.

20.
Int J Biol Macromol ; 258(Pt 1): 128702, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072341

RESUMO

Phellinus linteus polysaccharides exhibit antitumor, immunomodulatory, anti-inflammatory, and antioxidant properties, mitigate insulin resistance, and enhance the diversity and abundance of gut microbiota. However, the bioactivities of P. linteus polysaccharides vary owing to the complex structure, thereby, limiting their application. Various processing strategies have been employed to modify them for improving the functional properties and yield. Herein, we compare the primary modes of extraction and purification employed to improve the yield and purity, review the structure-activity relationships, and discuss the application of P. linteus polysaccharides using nano-carriers for the encapsulation and delivery of various drugs to improve bioactivity. The limitations and future perspectives are also discussed. Exploring the bioactivity, structure-activity relationship, processing methods, and delivery routes of P. linteus polysaccharides will facilitate the development of functional foods and dietary supplements rich in P. linteus polysaccharides.


Assuntos
Basidiomycota , Basidiomycota/química , Polissacarídeos/química , Relação Estrutura-Atividade , Sistemas de Liberação de Medicamentos
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