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1.
G3 (Bethesda) ; 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34586388

RESUMO

Ganoderma leucocontextum, a newly discovered species of Ganodermataceae in China, has diverse pharmacological activities. G. leucocontextum was widely cultivated in southwest China, but the systematic genetic study has been impeded by the lack of a reference genome. Herein, we present the first whole-genome assembly of G. leucocontextum based on the Illumina and Nanopore platform from high-quality DNA extracted from a monokaryon strain (DH-8). The generated genome was 50.05 Mb in size with a N50 scaffold size of 3.06 Mb, 78,206 coding sequences and 13,390 putative genes. Genome completeness was assessed using the Benchmarking Universal Single-Copy Orthologs (BUSCO) tool, which identified 96.55% of the 280 Fungi BUSCO genes. Furthermore, differences in functional genes of secondary metabolites (terpenoids) were analyzed between G. leucocontextum and G. lucidum. G. leucocontextum has more genes related to terpenoids synthesis compared to G. lucidum, which may be one of the reasons why they exhibit different biological activities. This is the first genome assembly and annotation for G. leucocontextum, which would enrich the toolbox for biological and genetic studies in G. leucocontextum.

2.
Antioxidants (Basel) ; 10(7)2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34356378

RESUMO

Two low-molecular-weight polysaccharides (GLP-1 and GLP-2) were purified from Ganoderma leucocontextum fruiting bodies, and their physicochemical properties and antioxidant activities were investigated and compared in this study. The results showed that GLP-1 and GLP-2 were mainly composed of mannose, glucose, galactose, xylose, and arabinose, with weight-average molecular weights of 6.31 and 14.07 kDa, respectively. Additionally, GLP-1 and GLP-2 had a similar chain conformation, crystal structure, and molecular surface morphology. Moreover, GLP-1 exhibited stronger antioxidant activities than GLP-2 in five different assays: 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), hydroxyl radical, superoxide anion radical, ferric reducing antioxidant power (FRAP), and oxygen radical antioxidant capacity (ORAC). The main linkage types of GLP-1 were found to be →4)-α-D-Glcp-(1→, →4)-ß-D-Glcp-(1→, →3)-ß-D-Glcp-(1→, →6)-ß-D-Galp-(1→, →6)-α-D-Glcp-(1→, →4,6)-α-D-Glcp-(1→, and Glcp-(1→ by methylation analysis and nuclear magnetic resonance (NMR) spectroscopy. In addition, GLP-1 could protect NIH3T3 cells against tert-butyl hydroperoxide (tBHP)-induced oxidative damage by increasing catalase (CAT) and glutathione peroxidase (GSH-Px) activities, elevating the glutathione/oxidized glutathione (GSH/GSSG) ratio, and decreasing the malondialdehyde (MDA) level. These findings indicated that GLP-1 could be explored as a potential antioxidant agent for application in functional foods.

3.
Bioorg Chem ; 115: 105276, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426146

RESUMO

Bioassay-guided fractionation led to the isolation of a series of triterpenoids (1-46) including 12 new ones (1-12) from the mushroom Inonotus obliquus. The structures of all the compounds were elucidated by spectroscopic analysis as well as by comparison with literature data. Triterpenoids 1-3, 6, 7, 16, 24, 25, 27, 38, 43, 44 and 46 showed strong α-glucosidase inhibition, with IC50 values from 11.5 to 81.8 µM. Their structure-activity relationships were discussed. Inonotusol F (24) showed the strongest inhibitory activity and it presented noncompetitive inhibition against α-glucosidase. Molecular docking and molecular dynamics stimulation further demonstrated that GLU302 and PHE298 were key amino acids for the inhibition of inonotusol F (24) towards α-glucosidase. This study indicates the vital role of triterpenoids in explaining hypoglycemic effect of Inonotus obliquus and provides important evidence for further development and utilization of this mushroom.

4.
Genes (Basel) ; 12(4)2021 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-33805512

RESUMO

Ganoderma lucidum spores (GLS), the mature germ cells ejected from the abaxial side of the pileus, have diverse pharmacological effects. However, the genetic regulation of sporulation in this fungus remains unknown. Here, samples corresponding to the abaxial side of the pileus were collected from strain YW-1 at three sequential developmental stages and were then subjected to a transcriptome assay. We identified 1598 differentially expressed genes (DEGs) and found that the genes related to carbohydrate metabolism were strongly expressed during spore morphogenesis. In particular, genes involved in trehalose and malate synthesis were upregulated, implying the accumulation of specific carbohydrates in mature G. lucidum spores. Furthermore, the expression of genes involved in triterpenoid and ergosterol biosynthesis was high in the young fruiting body but gradually decreased with sporulation. Finally, spore development-related regulatory pathways were explored by analyzing the DNA binding motifs of 24 transcription factors that are considered to participate in the control of sporulation. Our results provide a dataset of dynamic gene expression during sporulation in G. lucidum. They also shed light on genes potentially involved in transcriptional regulation of the meiotic process, metabolism pathways in energy provision, and ganoderic acids and ergosterol biosynthesis.


Assuntos
Carboidratos/fisiologia , Proteínas Fúngicas/metabolismo , Meiose , Reishi/fisiologia , Metabolismo Secundário , Esporos Fúngicos/fisiologia , Transcriptoma , Proteínas Fúngicas/genética , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica
5.
Int J Med Mushrooms ; 23(4): 71-80, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822509

RESUMO

A mycochemical investigation on the medicinal mushroom Amauroderma rugosum led to the isolation of 30 compounds, including 14 sterols, 6 phenolic constituents, 5 unsaturated fatty acids, and 5 other compounds. The structures of these compounds were elucidated by comparison of their nuclear magnetic resonance spectroscopic and mass spectrometry data with literature data. Among them, compound 27 was obtained as a new natural compound, and compounds 2-4, 7-13, and 15-30 were isolated from the genus Amauroderma for the first time. Sterols and unsaturated fatty acids showed anti-inflammatory and antiproliferative activities in vitro. Compounds 5 and 6 showed the highest inhibitory effect on nitric oxide production in lipopolysaccharide-induced murine macrophage RAW264.7 cells, with half maximal inhibitory concentration (IC50) values of 27.6 ± 2.1 µM and 15.3 ± 2.0 µM respectively. Compound 17 exhibited the strongest inhibition against HepG2 and MDA-MB-231 cell lines, with IC50 values < 25 µM. This study not only enriches the understanding of the diversity of chemical constituents in A. rugosum, but it also provides a basis for further development and utilization of A. rugosum as a source of new potential antitumor or anti-inflammatory chemotherapy agents.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Lipídeos/isolamento & purificação , Polyporaceae/química , Animais , Anti-Inflamatórios/isolamento & purificação , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Células Hep G2 , Humanos , Concentração Inibidora 50 , Lipídeos/farmacologia , Camundongos , Células RAW 264.7
6.
Artigo em Inglês | MEDLINE | ID: mdl-33859713

RESUMO

Ganoderma lucidum (Leyss.Fr.) Karst is one of the well-known medicinal macrofungi all over the world, and mounting researches have focused on the polysaccharides derived from the spores of G. lucidum. In the present study, BALB/c mice (n = 8-10) were administered with crude polysaccharides of G. lucidum spores (CPGS) and the refined polysaccharides of G. lucidum spores (RPGS) for 30 days to investigate their effect on the adaptive immune system. Results showed that CPGS and RPGS displayed diverse effects on the lymphocyte activity in the spleen. The splenocyte proliferation activity upon mitogen was suppressed by CPGS and RPGS, while the NK cell's tumor-killing ability was promoted by CPGS. Both CPGS and RPGS could increase the proportion of naïve T cells in thymus, but only RPGS significantly uplifted the percentage of T cells, as well as the T cell subsets, in peripheral blood, and promoted the activation by upregulating the expression of costimulatory factor CD28. Moreover, 16S sequencing results showed that the effects of CPGS and RPGS were closely related to the regulation of gut microbiota. ß-diversity of the microbiome was evidently changed by CPGS and RPGS. The phytoestrogen/polysaccharide-metabolizing bacteria (Adlercreutzia, Parabacteroides, and Prevotella), and an unclassified Desulfovibrionaceae, were remarkably enriched by CPGS or RPGS, and functions involving carbohydrate metabolism, membrane transport, and lipid metabolism were regulated. Moreover, the enrichments of Adlercreutzia, Prevotella, and Desulfovibrionaceae were positively related to the immune regulation by CPGS and RPGS, while that of Parabacteroides displayed a negative correlation. These findings suggested a promising effect of the polysaccharide from sporoderm-broken spore of G. lucidum in immune regulation to promote health control.

7.
Pharm Biol ; 59(1): 275-286, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33651969

RESUMO

CONTEXT: Poria coco F.A.Wolf (Polyporaceae) dispels dampness and promotes diuresis implying hypouricaemic action. OBJECTIVE: To examine hypouricaemic action of Poria coco. MATERIALS AND METHODS: Ethanol extract (PCE) was prepared by extracting the sclerotium of P. cocos with ethanol, and the water extract (PCW) was produced by bathing the remains with water. PCE and PCW (50, 100 and 200 mg/kg, respectively) were orally administered to hyperuricemic Kunming mice (n = 8) to examine its hypouricaemic effect. Also, molecular docking was performed. RESULTS: P. cocos showed excellent hypouricaemic action, decreasing the serum uric acid of hyperuricaemia (HUA) control (526 ± 112 µmol/L) to 178 ± 53, 153 ± 57 and 151 ± 62 µmol/L (p < 0.01) by PCE and 69 ± 23, 63 ± 15 and 62 ± 20 µmol/L (p < 0.01) by PCW, respectively. According to SCrs, BUNs and H&E staining, PCE and PCW partially attenuated renal dysfunction caused by HUA. They presented no negative effects on ALT, AST and ALP activities. They elevated ABCG2 (ATP-binding cassette super-family G member 2) mRNA and protein expression in comparison to HUA control. In molecular docking, compound 267, 277, 13824, 15730 and 5759 were predicted as the top bioactives of P. cocos against HUA, which even presented better scores than the positive compound, oestrone 3-sulfate. DISCUSSION AND CONCLUSIONS: This paper demonstrated the hypouricaemic and nephroprotective effects of P. cocos in hyperuricemic mice by up-regulating ABCG2. These results may be useful for the development of a hypouricaemic agent.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Hiperuricemia/tratamento farmacológico , Extratos Vegetais/farmacologia , Wolfiporia/química , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/química , Hiperuricemia/complicações , Nefropatias/etiologia , Nefropatias/prevenção & controle , Masculino , Camundongos , Simulação de Acoplamento Molecular , Extratos Vegetais/administração & dosagem , Regulação para Cima/efeitos dos fármacos , Ácido Úrico/sangue , Água/química
8.
Biomed Pharmacother ; 130: 110539, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768880

RESUMO

Side effects of chemotherapy are burning questions for physicians and patients involved in cancers. Ganoderma lucidum is a widely consumed traditional Chinese medicine and edible mushroom with multiple functional properties. The present study aims to investigate the potential of polysaccharides from spore of G. lucidum (SGP) on small intestinal barrier function recovery against paclitaxel (PTX) challenge in a breast cancer mice model and IEC-6 cell line. The 4T1 tumor-bearing mice were treated with PTX together with four-week daily oral administration of SGP. Results indicated that combination of PTX and SGP reversed body weight lost and remolded the histology of small intestine, accompanied with promoted proliferation but suppressed apoptosis in intestinal cells. Intestinal barrier function was enhanced by the combination as indicated by reduced endotoxemia and the up-regulation of tight junction proteins, including Zonula occludens-1 (ZO-1), E-cadherin, ß-catenin and Occludin. The protection of SGP was further confirmed in IEC-6 cells affected by PTX in vitro. The combination treatment prevented PTX-induced apoptosis in IEC-6 by inhibiting microtubule polymerization, and the aforementioned tight junction proteins were also upregulated. These findings suggest a promising protective effect of SGP against small intestinal barrier injury caused by PTX, highlighting its clinical implication against the chemotherapy side effects.


Assuntos
Antineoplásicos Fitogênicos/toxicidade , Apoptose/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos , Paclitaxel/toxicidade , Polissacarídeos/farmacologia , Reishi/química , Esporos Fúngicos/química , Animais , Antineoplásicos Fitogênicos/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Feminino , Humanos , Mucosa Intestinal/citologia , Camundongos , Camundongos Endogâmicos BALB C , Paclitaxel/antagonistas & inibidores , Polissacarídeos/química , Proteínas de Junções Íntimas/biossíntese , Perda de Peso/efeitos dos fármacos
9.
Front Pharmacol ; 11: 606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411003

RESUMO

Triple-negative breast cancer (TNBC) is an aggressive disease with worst prognosis than other subtypes of breast cancer. Owing to the lack of hormone receptors and HER2 expression on TNBC cells, patients do not have targeted therapy options available with other breast cancer subtypes. Extensive efforts have been made to identify novel therapeutics against TNBC. Interestingly, recent studies had shown that plant-derived natural products could modulate the autophagy and induce the breast cancer cells death. Seed of Brucea javanica has been used as an important traditional Chinese medicine against cancers. In the present study, the anti-breast cancer potential of ethanol crude extracts from B. javanica seed (BJE) was explored. Data demonstrated that BJE could inhibit the TNBC cell line MDA-MB-231 proliferation and induced apoptosis. In the cells exposed to BJE, protein expressions of UNC-51-like kinase-1 (ULK1) and Beclin-1 and the ratio of light chain 3 II/I (LC3 II/I) were reduced, while the expression of p62 was increased, indicating an inhibition on autophagy. Moreover, BJE promoted the phosphorylation of mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase (PI3K), and Akt in MDA-MB-231. BJE also suppressed the MDA-MB-231 tumor growth in vivo. Coincide with the results in vitro, autophagy in the tumor tissue was weakened as indicated by decreased ratio of LC 3 II/I and Beclin-1 accompanied by enhanced phosphorylation of mTOR, which confirmed that autophagy restraint via the PI3K/Akt/mTOR signaling pathway contributes to the suppression by BJE. Notably, no noticeable toxicity in non-targeted organs was found, including small intestine, liver, and kidney. Taken together, this study revealed anti-breast cancer activity of BJE based on autophagy restraint, highlighting its clinical importance as a novel natural agent against TNBC.

10.
Biomed Pharmacother ; 127: 110212, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32422567

RESUMO

Inflammatory bowel disease (IBD) is a chronic relapsing inflammation involving the gut system, and disequilibrium of T helper (Th) cell paradigm has been recognized as critical pathogenesis. Pycnoporus sanguineus (L.) Murrill is a species of the white-rot basidiomycetes listed as food- and cosmetic-grade microorganisms. In this study, anti-inflammatory activity of the ethanol extract from P. sanguineus (PSE) was investigated in dextran sulfate sodium (DSS)-induced experimental colitis model. PSE recovered the DSS-caused weight loss, reversed the colon shortening, and ameliorated the histopathological lesion in colon, resulting in lower disease activity index (DAI). Levels of serumal lipopolysaccharide (LPS), colonic myeloperoxidase (MPO) in the colitis-suffering mice were declined by PSE treatment. PSE also improved the mucosal integrity by enhancing the expression of tight junction and adherens junction proteins in the colon, including ZO-1, occludin, claudin-1, and E-cadherin. Besides, PSE reduced helper T cells (Th) in the colon, together with an evident decrease of several Th cell-related cytokines. Moreover, it was found that in vitro, PSE suppressed T cells and the Th subset upon Concanavalin A (ConA)-stimulation by inducing apoptosis. In summary, PSE displayed a remission on the colitis-related inflammation, which would possibly rely on the epithelial barrier restoration by suppressing Th cells via apoptosis induction, highlighting a promising potential in the treatment for IBD.


Assuntos
Colite/tratamento farmacológico , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Polyporaceae/química , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Apoptose/efeitos dos fármacos , Colite/patologia , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Etanol/química , Inflamação/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Linfócitos T Auxiliares-Indutores/imunologia
11.
Int J Med Mushrooms ; 21(7): 703-711, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679304

RESUMO

Ganoderma mushrooms are widely used in clinical therapies and functional foods. The antidiabetic effect of Ganoderma has become a research hot spot in recent decades. To search for a superior antidiabetic Ganoderma extract, five common Ganoderma species (G. lucidum, G. sinense, G. tsugae, G. applanatum, and G. leucocontextum) were investigated. A total of 10 fractions, including a total triterpenes fraction and a crude polysaccharides fraction for each, were prepared for further assays. Activities of α-glucosidase and α-amylase are inhibited dominantly by triterpenes from all five Ganoderma species rather than the polysaccharides. G. lucidum triterpenes inhibits α-glucosidase and α-amylase most significantly with IC50 values of 10.02 ± 0.95 µg/mL and 31.82 ± 4.30 µg/mL. Even more, triterpenes content was positively correlated with anti-α-glucosidase and anti-α-amylase activities. Therefore, triterpenes were considered to be the active compounds in inhibiting α-glucosidase and α-amylase activity. It is hoped that the results will provide more systematic information for the application of Ganoderma in the functional food and traditional medicine industries in the future.


Assuntos
Diabetes Mellitus Tipo 2/enzimologia , Ganoderma/química , Inibidores de Glicosídeo Hidrolases/farmacologia , alfa-Amilases/antagonistas & inibidores , Misturas Complexas/farmacologia , Polissacarídeos Fúngicos/farmacologia , Ganoderma/classificação , Fármacos Gastrointestinais , Humanos , Hipoglicemiantes/farmacologia , Concentração Inibidora 50 , Triterpenos/farmacologia , alfa-Glucosidases
12.
Molecules ; 23(10)2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30336599

RESUMO

Conventionally, benzophenone-type molecules are beneficial for alleviating the UV exposure of humans. More importantly, various compounds with this skeleton have demonstrated various biological activities. In this paper, we report the anti-hyperuricemic effect of the benzophenone compound 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (HMS). Preliminarily, its molecular docking score and xanthine oxidase (XOD) inhibition suggested a good anti-hyperuricemic effect. Then, its anti-hyperuricemic effect, primary mechanisms and general toxicity were examined on a hyperuricemic mouse model which was established using potassium oxonate and hypoxanthine together. HMS demonstrated a remarkable anti- hyperuricemic effect which was near to that of the control drugs, showing promising perspective. General toxicity was assessed and it showed no negative effects on body weight growth and kidney function. Moreover, anti-inflammatory action was observed for HMS via spleen and thymus changes. Its anti-hyperuricemic mechanisms may be ascribed to its inhibition of XOD and its up-regulation of organic anion transporter 1 (OAT1) and down-regulation of glucose transporter 9 (GLUT9).


Assuntos
Benzofenonas/administração & dosagem , Proteínas Facilitadoras de Transporte de Glucose/genética , Hiperuricemia/tratamento farmacológico , Proteína 1 Transportadora de Ânions Orgânicos/genética , Xantina Oxidase/genética , Animais , Benzofenonas/química , Peso Corporal/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hiperuricemia/patologia , Hipoxantina/administração & dosagem , Rim/efeitos dos fármacos , Camundongos , Simulação de Acoplamento Molecular , Ácido Oxônico/administração & dosagem , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Xantina Oxidase/antagonistas & inibidores
13.
Int J Mol Sci ; 19(10)2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30340390

RESUMO

Inonotus obliquus is an edible mushroom and also a remedy against various diseases, especially metabolic syndrome. In this paper we report the actions of an ethanol extract of I. obliquus (IOE) against hyperuricemia in hyperuricemic mice, and the screen of bioactives. The extract (IOE) was prepared by extracting I. obliquus at 65 °C with ethanol, and characterized by HPLC. IOE at low, middle, and high doses reduced serum uric acid (SUA) of hyperuricemic mice (353 µmol/L) to 215, 174, and 152 µmol/L (p < 0.01), respectively, showing similar hypouricemic effectiveness to the positive controls. IOE showed a non-toxic impact on kidney and liver functions. Of note, IOE suppressed xanthine oxidase (XOD) activity in serum and liver, and also down-regulated renal uric acid transporter 1 (URAT1). Four compounds hit highly against XOD in molecular docking. Overall, the four compounds all occupied the active tunnel, which may inhibit the substrate from entering. The IC50 of betulin was assayed at 121.10 ± 4.57 µM, which was near to that of allopurinol (148.10 ± 5.27 µM). Betulin may be one of the anti-hyperuricemia bioactives in I. obliquus.


Assuntos
Basidiomycota/química , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Hiperuricemia/enzimologia , Modelos Moleculares , Xantina Oxidase/química , Animais , Descoberta de Drogas , Hiperuricemia/sangue , Hiperuricemia/tratamento farmacológico , Camundongos , Relação Quantitativa Estrutura-Atividade , Xantina Oxidase/antagonistas & inibidores
14.
Front Pharmacol ; 9: 498, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867500

RESUMO

Agrocybe aegerita has long been utilized for promoting diuresis in traditional Chinese medicine (TCM) with a close correlation to hypouricemia. Ethanol (AAE) and water (AAW) extracts of the compound led to a remarkable decrease in serum uric acid levels (SUA) in hyperuricemia mice, approaching that of the normal control. Both AAE and AAW exhibited suppression effects on hepatic xanthine oxidase (XOD) activities and elevation effects on renal OAT1 (organic anion transporter 1). However, only little negative impact was observed on the inner organ functions. The molecular docking was used to screen our in-home compound database for A. aegerita, and four compounds including 2-formyl-3,5-dihydroxybenzyl acetate, 2,4-dihydroxy-6-methylbenzaldehyde, 2-(6-hydroxy-1H-indol-3-yl)acetamide, and 6-hydroxy-1H-indole-3-carbaldehyde (HHC) were identified as potential active compounds. Their inhibitory mechanism on XOD might be attributed to their localization in the tunnel for the entrance of substrates to XOD active site, preventing the entrance of the substrates. To confirm the activity of the screened compounds experimentally, HHC was selected due to its high ranking and availability. The assaying result suggested the significant inhibitory activity of HHC on XOD. Also, these compounds were predicted to carry good ADME (absorption, distribution, metabolism, and excretion) properties, thereby necessitating further investigation. The current results provided an insight into the hypouricemic effects of macrofungi and their bioactives, which might provide the significant theoretical foundation for identifying and designing novel hypouricemia compounds.

15.
Int J Mol Sci ; 19(5)2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735945

RESUMO

Searching novel hypouricemic agents of high efficacy and safety has attracted a great attention. Previously, we reported the hypouricemic effect of Ganoderma applanatum, but its bioactives, was not referred. Herein, we report the hypouricemic effect of 2,5-dihydroxyacetophenone (DHAP), a compound screened from Ganoderma applanatum computationally. Serum parameters, such as uric acid (SUA), xanthine oxidase (XOD) activity, blood urea nitrogen (BUN), and creatinine were recorded. Real-time reverse transcription PCR (RT-PCR) and Western blot were exploited to assay RNA and protein expressions of organic anion transporter 1 (OAT1), glucose transporter 9 (GLUT9), uric acid transporter 1 (URAT1), and gastrointestinal concentrative nucleoside transporter 2 (CNT2). DHAP at 20, 40, and 80 mg/kg exerted excellent hypouricemic action on hyperuricemic mice, reducing SUA from hyperuricemic control (407 ± 31 μmol/L, p < 0.01) to 180 ± 29, 144 ± 13, and 139 ± 31 μmol/L, respectively. In contrast to the renal toxic allopurinol, DHAP showed some kidney-protective effects. Moreover, its suppression on XOD activity, in vivo and in vitro, suggested that XOD inhibition may be a mechanism for its hypouricemic effect. Given this, its binding mode to XOD was explored by molecular docking and revealed that three hydrogen bonds may play key roles in its binding and orientation. It upregulated OAT1 and downregulated GLUT9, URAT1, and CNT2 too. In summary, its hypouricemic effect may be mediated by regulation of XOD, OAT1, GLUT9, URAT1, and CNT2.


Assuntos
Acetofenonas/química , Acetofenonas/uso terapêutico , Ganoderma/química , Supressores da Gota/química , Supressores da Gota/uso terapêutico , Hiperuricemia/tratamento farmacológico , Animais , Nitrogênio da Ureia Sanguínea , Hiperuricemia/sangue , Masculino , Camundongos , Simulação de Acoplamento Molecular , Ácido Úrico/sangue , Xantina Oxidase/sangue
16.
Am J Chin Med ; 46(3): 585-599, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29595077

RESUMO

Ethanol and water extracts of Armillaria mellea were prepared by directly soaking A. mellea in ethanol (AME) at 65[Formula: see text]C, followed by decocting the remains in water (AMW) at 85[Formula: see text]C. Significantly, AME and AMW at 30, 60 and 120[Formula: see text]mg/kg exhibited excellent hypouricemic actions, causing remarkable declines from hyperuricemic control (351[Formula: see text][Formula: see text]mol/L, [Formula: see text]) to 136, 130 and 115[Formula: see text][Formula: see text]mol/L and 250, 188 and 152[Formula: see text][Formula: see text]mol/L in serum uric acid, correspondingly. In contrast to the evident renal toxicity of allopurinol, these preparations showed little impacts. Moreover, they showed some inhibitory effect on XOD (xanthine oxidase) activity. Compared with hyperuricemic control, protein expressions of OAT1 (organic anion transporter 1) were significantly elevated in AME- and AMW-treated mice. The levels of GLUT9 (glucose transporter 9) expression were significantly decreased by AMW. CNT2 (concentrative nucleoside transporter 2), a key target for purine absorption in gastrointestinal tract was involved in this study, and was verified for its innovative role. Both AME and AMW down-regulated CNT2 proteins in the gastrointestinal tract in hyperuricemic mice. As they exhibited considerable inhibitory effects on XOD, we selected XOD as the target for virtual screening by using molecular docking, and four compounds were hit with high ranks. From the analysis, we concluded that hydrogen bond, Pi-Pi and Pi-sigma interactions might play important roles for their orientations and locations in XOD inhibition.


Assuntos
Armillaria/química , Regulação para Baixo/efeitos dos fármacos , Hiperuricemia/tratamento farmacológico , Hiperuricemia/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/genética , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Fitoterapia , Extratos Vegetais/uso terapêutico , Animais , Etanol , Trato Gastrointestinal/metabolismo , Expressão Gênica/efeitos dos fármacos , Proteínas Facilitadoras de Transporte de Glucose/genética , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Ligação de Hidrogênio , Hiperuricemia/metabolismo , Masculino , Camundongos , Extratos Vegetais/farmacologia , Ácido Úrico/sangue , Água , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
17.
Front Microbiol ; 9: 58, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29422889

RESUMO

Recently, we've reported the anti-hyperuricemic effects of Cordyceps militaris. As a characteristic compound of C. militaris, we hypothesized that cordycepin may play a role in preventing hyperurecimia. Remarkably, cordycepin produced important anti-hyperuricemic actions, decreasing SUA (serum uric acid) to 216, 210, and 203 µmol/L (P < 0.01) at 15, 30, and 60 mg/kg in comparison of hyperuricemic control (337 µmol/L), closing to normal control (202 µmol/L). Elisa, RT-PCR and western blot analysis demonstrated that the actions may be attributed to its downregulation of uric acid transporter 1 (URAT1) in kidney. Serum creatinine levels and blood urine nitrogen and liver, kidney, and spleen coefficients demonstrated that cordycepin may not impact liver, renal, and spleen functions. In addition, we used computational molecular simulation to investigate the binding mechanism of cordycepin. Of which, van der Waals interaction dominated the binding. Residues TRP290, ARG17, ALA408, GLY411, and MET147 contributed mainly on nonpolar energy. This provided the theoretical guidance to rationally design and synthesis novel URAT1 inhibitors.

18.
Front Chem ; 5: 85, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29164102

RESUMO

This study was carried out to isolate chemical constituents from the lipid enriched fraction of Ganoderma lucidum extract and to evaluate their anti-proliferative effect on tumor cells and human umbilical vein endothelial cells (HUVECs). Ergosterol derivatives (1-14) were isolated and purified from the lipid enriched fraction of G. lucidum. Their chemical structures were established by spectroscopic analyses or by comparison of mass and NMR spectral data with those reported previously. Amongst, compound 1 was purified and identified as a new one. All the compounds were evaluated for their anti-proliferative effect on human tumor cells and HUVECs in vitro. Compounds 9-13 displayed inhibitory activity against two types of human tumor cells and HUVECs, which indicated that these four compounds had both anti-tumor and anti-angiogenesis activities. Compound 2 had significant selective inhibition against two tumor cell lines, while 3 exhibited selective inhibition against HUVECs. The structure-activity relationships for inhibiting human HepG2 cells were revealed by 3D-QASR. Ergosterol content in different parts of the raw material and products of G. lucidum was quantified. This study provides a basis for further development and utilization of ergosterol derivatives as natural nutraceuticals and functional food ingredients, or as source of new potential antitumor or anti-angiogenesis chemotherapy agent.

19.
Antiviral Res ; 144: 273-280, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28629987

RESUMO

Early events in herpes simplex virus type 1 (HSV-1) infection reactivate latent human immunodeficiency virus, Epstein-Barr virus, and human papillomavirus in the presence of acyclovir (ACV). The common use of nucleoside analog medications, such as ACV and pencyclovir, has resulted in the emergence of drug-resistant HSV-1 strains in clinical therapy. Therefore, new antiherpetics that can inhibit early events in HSV-1 infection should be developed. An example of this treatment is Houttuynia cordata Thunb. water extract, which can inhibit HSV-1 infection through multiple mechanisms. In this study, the anti-HSV-1 activity of Houttuynoid A, a new type of flavonoid isolated from H. cordata, was investigated. Three different assays confirmed that this compound could exhibit strong in vitro anti-HSV-1 activity. One assay verified that this compound could inhibit HSV-1 multiplication and prevent lesion formation in a HSV-1 infection mouse model. Mechanism analysis revealed that this compound could inactivate HSV-1 infectivity by blocking viral membrane fusion. Moreover, Houttuynoid A exhibited antiviral activities against other alpha herpes viruses, such as HSV-2 and varicella zoster virus (VZV). In conclusion, Houttuynoid A may be a useful antiviral agent for HSV-1.


Assuntos
Antivirais/administração & dosagem , Flavonoides/administração & dosagem , Herpes Simples/prevenção & controle , Herpesvirus Humano 1/efeitos dos fármacos , Houttuynia/química , Animais , Antivirais/isolamento & purificação , Antivirais/farmacologia , Modelos Animais de Doenças , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 3/efeitos dos fármacos , Camundongos
20.
Oncotarget ; 8(6): 10071-10084, 2017 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-28052025

RESUMO

We conducted a study of Ganoderma lucidum metabolites and isolated 35 lanostane-type triterpenoids, including 5 new ganoderols (1-5). By spectroscopy, we compared the structures of these compounds with known related compounds in this group. All of the isolated compounds were assayed for their effect against the human breast carcinoma cell line MDA-MB-231 and hepatocellular carcinoma cell line HepG2. Corresponding three-dimensional quantitative structure-activity relationship (3D-QSAR) models were built and analyzed using Discovery Studio. These results provide further evidence for anti-cancer constituents within Ganoderma lucidum, and may provide a theoretical foundation for designing novel therapeutic compounds.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Carpóforos/química , Neoplasias Hepáticas/tratamento farmacológico , Reishi/química , Triterpenos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/patologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Células Hep G2 , Humanos , Concentração Inibidora 50 , Neoplasias Hepáticas/patologia , Conformação Molecular , Simulação de Acoplamento Molecular , Relação Quantitativa Estrutura-Atividade , Triterpenos/química , Triterpenos/isolamento & purificação
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