基于广泛靶向代谢组学的竹黄活性成分分析
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摘要
竹黄是我国一种重要的药用真菌,在医学、农业、食品等方面应用广泛且前景可观。为深入挖掘竹黄中有药理活性的有效化学成分,了解其在生长发育过程中不同时期代谢物的变化规律,利用广泛靶向代谢组学技术检测了竹黄子座不同发育时期的代谢物,找出差异代谢物并进行代谢通路分析。从竹黄子座中共检测出612种代谢物,前期和中期特有27种代谢物。黄酮类、奎宁酸、香豆素等具有良好生物活性的化合物首次在竹黄中被检测到。筛选出的差异代谢物主要是脂质、氨基酸、核苷酸、黄酮类、萜类、有机酸等物质,其中黄酮和氨基酸类化合物占主要地位。通过对代谢通路富集分析,获得6条具有显著意义的代谢途径。黄酮类化合物被认为是除竹红菌素外与竹黄药效有重要联系的化合物。本研究为竹黄药用机理及有效成分深入研究提供了一定的理论基础,为竹黄有效成分的代谢途径解析提供参考。
Shiraia bambusicola is an important medicinal fungus in China, which has a wide applications in medicine, agriculture, food and other fields. The technique of widely-targeted metabolomics was used to detect metabolites produced by Shiraia bambusicola at various developmental stages for identifying differential metabolites and performing metabolic pathway analysis. A total of 612 metabolites were identified from Shiraia bambusicola, of which 27 unique metabolites were found in the early and medium developmental stages. Flavonoids, quinic acid, coumarin and other compounds with notable biological activity were detected for the first time. The differential metabolites selected mainly include lipid, amino acids, nucleotide, flavonoids,terpenoids, organic acids, etc. Among them, flavonoids and amino acids were prior to the others. Six significant metabolic pathways were obtained through enrichment analysis. Flavonoids are considered to be important compounds that are related to the medicinal value of Shiraia bambusicola in addition to hypocrellin.This result provides a basis for further study of the medicinal mechanism and active ingredients of Shiraia bambusicola.
Shiraia bambusicola is an important medicinal fungus in China, which has a wide applications in medicine, agriculture, food and other fields. The technique of widely-targeted metabolomics was used to detect metabolites produced by Shiraia bambusicola at various developmental stages for identifying differential metabolites and performing metabolic pathway analysis. A total of 612 metabolites were identified from Shiraia bambusicola, of which 27 unique metabolites were found in the early and medium developmental stages. Flavonoids, quinic acid, coumarin and other compounds with notable biological activity were detected for the first time. The differential metabolites selected mainly include lipid, amino acids, nucleotide, flavonoids,terpenoids, organic acids, etc. Among them, flavonoids and amino acids were prior to the others. Six significant metabolic pathways were obtained through enrichment analysis. Flavonoids are considered to be important compounds that are related to the medicinal value of Shiraia bambusicola in addition to hypocrellin.This result provides a basis for further study of the medicinal mechanism and active ingredients of Shiraia bambusicola.
引文
Chang JE,Cho HJ,Yi E,Kim DD,Jheon S,2016.Hypocrellin b and paclitaxel-encapsulated hyaluronic acid-ceramide nanoparticles for targeted photodynamic therapy in lung cancer.Journal of Photochemistry&Photobiology B:Biology,158(2):113-121
Chen W,Gong L,Guo ZL,Wang WS,Zhang HY,Liu XQ,Yu SB,Xiong LZ,Lou J,2013.A novel integrated method for large-scale detection,identification,and quantification of widely targeted metabolites:application in the study of rice metabolomics.Molecular Plant,6(6):1769-1780
Chen ZL,Yin ZQ,Zhang J,Ye WC,Zhao SX,2011.Research progress on the medicinal fungus Shiraia bambusicola.Asia-Pacific Traditional Medicine,7(7):160-163(in Chinese)
Cheng JC,Dai F,Zhou B,Yang L,Liu ZL,2007.Antioxidant activity of hydroxycinnamic acid derivatives in human low density lipoprotein:mechanism and structure-activity relationship.Food Chemistry,104(1):132-139
Chirumbolo S,2010.The role of quercetin,flavonols and flavones in modulating inflammatory cell function.Inflammation&Allergy Drug Targets,9(4):263-285
Clercq ED,2004.Antiviral drugs in current clinical use.Journal of Clinical Virology,30(2):115-133
Deschner EE,Ruperto J,Wong G,Newmark HL,1991.Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia.Carcinogenesis,12(7):1193-1196
Fang JN,Ye CQ,Liu YR,1982.Chemical investigation of new polysaccharides from Shiraia bambusicola.Acta Chimica Sinica,40(4):39-43(in Chinese)
Gauthier L,Atanasova-Penichon V,Chereau S,Richard-Forget F,2015.Metabolomics to decipher the chemical defense of cereals against Fusarium graminearum and deoxynivalenol accumulation.International Journal of Molecular Sciences,16(10):24839-24872
Haidari F,Keshavarz SA,Shahi MM,Mahboob SA,Rashidi MR,2011.Effects of parsley(Petroselinum crispum)and its flavonol constituents,kaempferol and quercetin,on serum uric acid levels,biomarkers of oxidative stress and liver xanthine oxidoreductase activity in oxonate-induced hyperuricemic rats.Iranian Journal of Pharmaceutical Research,10(4):811-819
Haidari F,Rashidi MR,Shahi MM,2012.Effects of orange juice and hesperetin on serum paraoxonase activity and lipid profile in hyperuricemic rats.Bioimpacts,2(1):39-45
Hu X,Shen LD,1992.The isolation and structure identification of chemical constituents of Shiraia bambusicola.West China Journal of Pharmaceutical Sciences,7(1):1-4(in Chinese)
Hudson JB,Zhou J,Chen J,Harris L,Yip L,Towers GHN,2010.Hypocrellin,from Hypocrella bambusae,is phototoxic to human immunodeficiency virus.Photochemistry&Photobiology,60(3):253-255
Jia XM,Xu XH,Zhuang BC,Lin HP,2006.The progress of biological research of medicinal fungus Shiraia bambusicola.Microbiology China,33(3):147-150(in Chinese)
Kontogiorgis CA,Savvoglou K,Hadjipavlou-Litina DJ,2006.Antiinflammatory and antioxidant evaluation of novel coumarin derivatives.Journal of Enzyme Inhibition and Medicinal Chemistry,21(1):21-29
Liang XH,Cai YJ,Liao XR,Wei ZY,2008.The progress of research on medicinal fungus Shiraia bambusicola.Journal of Food Science and Biotechnology,27(5):21-26(in Chinese)
Lin N,Sato T,Takayama Y,Mimaki Y,Sashida Y,Yano M,Ito A,2003.Novel anti-inflammatory actions of nobiletin,a citrus polymethoxy flavonoid,on human synovial fibroblasts and mouse macrophages.Biochemical Pharmacology,65(12):2065-2071
Lindon JC,Holmes E,Nicholson JK,2006.Metabonomics techniques and applications to pharmaceutical research and development.Pharmaceutical Research(Dordrecht),23(6):1075-1088
Ma C,Wang H,Xin L,Li H,Liu B,Xu G,2007.Analysis of Artemisia annua l.Volatile oil by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry.Journal of Chromatography A,1150(1):50-53
Manojkumar P,Ravi TK,Subbuchettiar G,2009.Synthesis of coumarin heterocyclic derivatives with antioxidant activity and in vitro cytotoxic activity against tumour cells.Acta Pharmaceutica,59(2):159-170
Murakami A,Nakamura Y,Torikai K,Tanaka T,Koshiba T,Koshimizu K,Kuwahara S,Takahashi Y,Ogawa K,Yano M,Tokuda H,Nishino H,Mimaki Y,Sashida Y,Kitanaka S,Ohigashi H,2000.Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation,oxidative stress,and tumor promotion in mice.Cancer Research,60(18):5059-5066
Newman DJ,Cragg GM,Snader KM.2003.Natural products as sources of new drugs over the period 1981-2002.Journal of Natural Products,66(7):1002-1037
Ouyang GC,Xue YL,1988.Physiological role and regulation of phenylpropanoid metabolism in plant.Plant Physiology Communications,1988(3):9-16(in Chinese)
Peluso MR,2006.Flavonoids attenuate cardiovascular disease,inhibit phosphodiesterase,and modulate lipid homeostasis in adipose tissue and liver.Experimental Biology&Medicine,231(8):1287-1299
Roohbakhsh A,Parhiz H,Soltani F,Rezaee R,Iranshahi M,2015.Molecular mechanisms behind the biological effects of hesperidin and hesperetin for the prevention of cancer and cardiovascular diseases.Life Sciences,124:64-74
Sawada Y,Akiyama K,Sakata A,Kuwahara A,Otsuki H,Sakurai T,Saito K,Hirai MY,2009.Widely targeted metabolomics based on large-scale ms/ms data for elucidating metabolite accumulation patterns in plants.Plant and Cell Physiology,50(1):37-47
Shen YX,Cai XG,Gao ZH,2002.Studies on the chemical constituents of Shiraia bambusicola.China Journal of Chinese Materia Medica,27(9):674-677(in Chinese)
Srinivasan M,Sudheer AR,Menon VP,2007.Recent advances in Indian herbal drug research Guest Editor:Thomas Paul Asir Devasagayam ferulic acid:therapeutic potential through its antioxidant property.Journal of Clinical Biochemistry&Nutrition,40(2):92-100
Steinmeyer S,Lee K,Jayaraman A,Alaniz RC,2015.Microbiota metabolite regulation of host immune homeostasis:a mechanistic missing link.Current Allergy and Asthma Reports,15(5):524
Su MY,Niu JL,Li L,Yuan CG,Lu YH,2011.In vitro anti-tumor activity of nobiletin against five human cancer cell lines and its mechanism.Chinese Traditional Patent Medicine,2011(9):1479-1483(in Chinese)
Wang DD,Zhang LX,Huang XR,Wang X,Yang RN,Mao J,Wang XF,Wang XP,Zhang Q,Li P,2018.Identification of nutritional components in black sesame determined by widely targeted metabolomics and traditional Chinese medicines.Molecules,23:1180-1192
Wang X,Leung AW,Jiang Y,Yu H,Li X,Xu C,2012.Hypocrellin b-mediated sonodynamic action induces apoptosis of hepatocellular carcinoma cells.Ultrasonics,52(4):543-546
Xu GW,Lu X,Yang SL,2007.Recent advances in metabonomics.Acta Academiae Medicinae Sinicae,21(4):316-320(in Chinese)
Zhang Q,Zhao XH,Wang ZJ,2009.Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line(kyse-510)by induction of G2/Marrest and apoptosis.Toxicology in vitro,23(5):797-807
Zhao CG,Zhang LW,Wang H,Huang DY,2005.Study on anti-oxidation effects of cinnamic acid and its derivants.Food Science,26(1):218-222(in Chinese)
Zhao N,Chen SL,2018.Research progress on genetic diversity of Shiraia bambusicola,biosynthesis and anticancer activity of hypocrellin.Biotechnology Bulletin,34(4):16-23(in Chinese)
Zhenjun D,Lown JW,2010.Hypocrellins and their use in photosensitization.Photochemistry and Photobiology,52(3):609-616
Zou LQ,Wang CX,Kuang XJ,Li Y,Sun C,2016.Advance in flavonoids biosynthetic pathway and synthetic biology.China Journal of Chinese Material Medica,41(22):4124-4128(in Chinese)
陈占利,殷志琦,张健,叶文才,赵守训,2011.药用真菌竹黄的研究进展.亚太传统医药,7(7):160-163
方积年,叶淳渠,刘玉荣,1982.竹黄多糖的化学研究.化学学报,40(4):39-43
胡晓,沈联德,1992.竹黄化学成分的分离和结构鉴定.西药学杂志,7(1):1-4
贾小明,徐晓红,庄百川,林海萍,2006.药用竹黄菌的生物学研究进展.微生物学通报,33(3):147-150
梁晓辉,蔡宇杰,廖祥儒,魏兆媛,2008.药用真菌竹黄的研究进展.食品与生物技术学报,27(5):21-26
欧阳光察,薛应龙,1988.植物苯丙烷类代谢的生理意义及其调控.植物生理学通讯,1988(3):9-16
沈云修,菜先国,高宗华,2002.竹黄的化学成分研究.中国中药杂志,27(9):674-677
苏明媛,牛江龙,李林,袁才根,卢艳花,2011.川陈皮素的体外抑癌活性及其机制研究.中成药,2011(9):1479-1483
许国旺,路鑫,杨胜利,2007.代谢组学研究进展.中国医学科学院学报,29(6):701-711
赵春贵,张立伟,王晖,黄登宇,2005.肉桂酸及其衍生物抗氧化活性研究.食品科学,26(1):218-222
赵宁,陈双林,2018.竹黄遗传多样性与竹红菌素合成和抗癌作用的研究进展.生物技术通报,34(4):16-23
邹丽秋,王彩霞,匡雪君,李滢,孙超,2016.黄酮类化合物合成途径及合成生物学研究进展.中国中药杂志,41(22):4124-4128
Chen W,Gong L,Guo ZL,Wang WS,Zhang HY,Liu XQ,Yu SB,Xiong LZ,Lou J,2013.A novel integrated method for large-scale detection,identification,and quantification of widely targeted metabolites:application in the study of rice metabolomics.Molecular Plant,6(6):1769-1780
Chen ZL,Yin ZQ,Zhang J,Ye WC,Zhao SX,2011.Research progress on the medicinal fungus Shiraia bambusicola.Asia-Pacific Traditional Medicine,7(7):160-163(in Chinese)
Cheng JC,Dai F,Zhou B,Yang L,Liu ZL,2007.Antioxidant activity of hydroxycinnamic acid derivatives in human low density lipoprotein:mechanism and structure-activity relationship.Food Chemistry,104(1):132-139
Chirumbolo S,2010.The role of quercetin,flavonols and flavones in modulating inflammatory cell function.Inflammation&Allergy Drug Targets,9(4):263-285
Clercq ED,2004.Antiviral drugs in current clinical use.Journal of Clinical Virology,30(2):115-133
Deschner EE,Ruperto J,Wong G,Newmark HL,1991.Quercetin and rutin as inhibitors of azoxymethanol-induced colonic neoplasia.Carcinogenesis,12(7):1193-1196
Fang JN,Ye CQ,Liu YR,1982.Chemical investigation of new polysaccharides from Shiraia bambusicola.Acta Chimica Sinica,40(4):39-43(in Chinese)
Gauthier L,Atanasova-Penichon V,Chereau S,Richard-Forget F,2015.Metabolomics to decipher the chemical defense of cereals against Fusarium graminearum and deoxynivalenol accumulation.International Journal of Molecular Sciences,16(10):24839-24872
Haidari F,Keshavarz SA,Shahi MM,Mahboob SA,Rashidi MR,2011.Effects of parsley(Petroselinum crispum)and its flavonol constituents,kaempferol and quercetin,on serum uric acid levels,biomarkers of oxidative stress and liver xanthine oxidoreductase activity in oxonate-induced hyperuricemic rats.Iranian Journal of Pharmaceutical Research,10(4):811-819
Haidari F,Rashidi MR,Shahi MM,2012.Effects of orange juice and hesperetin on serum paraoxonase activity and lipid profile in hyperuricemic rats.Bioimpacts,2(1):39-45
Hu X,Shen LD,1992.The isolation and structure identification of chemical constituents of Shiraia bambusicola.West China Journal of Pharmaceutical Sciences,7(1):1-4(in Chinese)
Hudson JB,Zhou J,Chen J,Harris L,Yip L,Towers GHN,2010.Hypocrellin,from Hypocrella bambusae,is phototoxic to human immunodeficiency virus.Photochemistry&Photobiology,60(3):253-255
Jia XM,Xu XH,Zhuang BC,Lin HP,2006.The progress of biological research of medicinal fungus Shiraia bambusicola.Microbiology China,33(3):147-150(in Chinese)
Kontogiorgis CA,Savvoglou K,Hadjipavlou-Litina DJ,2006.Antiinflammatory and antioxidant evaluation of novel coumarin derivatives.Journal of Enzyme Inhibition and Medicinal Chemistry,21(1):21-29
Liang XH,Cai YJ,Liao XR,Wei ZY,2008.The progress of research on medicinal fungus Shiraia bambusicola.Journal of Food Science and Biotechnology,27(5):21-26(in Chinese)
Lin N,Sato T,Takayama Y,Mimaki Y,Sashida Y,Yano M,Ito A,2003.Novel anti-inflammatory actions of nobiletin,a citrus polymethoxy flavonoid,on human synovial fibroblasts and mouse macrophages.Biochemical Pharmacology,65(12):2065-2071
Lindon JC,Holmes E,Nicholson JK,2006.Metabonomics techniques and applications to pharmaceutical research and development.Pharmaceutical Research(Dordrecht),23(6):1075-1088
Ma C,Wang H,Xin L,Li H,Liu B,Xu G,2007.Analysis of Artemisia annua l.Volatile oil by comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry.Journal of Chromatography A,1150(1):50-53
Manojkumar P,Ravi TK,Subbuchettiar G,2009.Synthesis of coumarin heterocyclic derivatives with antioxidant activity and in vitro cytotoxic activity against tumour cells.Acta Pharmaceutica,59(2):159-170
Murakami A,Nakamura Y,Torikai K,Tanaka T,Koshiba T,Koshimizu K,Kuwahara S,Takahashi Y,Ogawa K,Yano M,Tokuda H,Nishino H,Mimaki Y,Sashida Y,Kitanaka S,Ohigashi H,2000.Inhibitory effect of citrus nobiletin on phorbol ester-induced skin inflammation,oxidative stress,and tumor promotion in mice.Cancer Research,60(18):5059-5066
Newman DJ,Cragg GM,Snader KM.2003.Natural products as sources of new drugs over the period 1981-2002.Journal of Natural Products,66(7):1002-1037
Ouyang GC,Xue YL,1988.Physiological role and regulation of phenylpropanoid metabolism in plant.Plant Physiology Communications,1988(3):9-16(in Chinese)
Peluso MR,2006.Flavonoids attenuate cardiovascular disease,inhibit phosphodiesterase,and modulate lipid homeostasis in adipose tissue and liver.Experimental Biology&Medicine,231(8):1287-1299
Roohbakhsh A,Parhiz H,Soltani F,Rezaee R,Iranshahi M,2015.Molecular mechanisms behind the biological effects of hesperidin and hesperetin for the prevention of cancer and cardiovascular diseases.Life Sciences,124:64-74
Sawada Y,Akiyama K,Sakata A,Kuwahara A,Otsuki H,Sakurai T,Saito K,Hirai MY,2009.Widely targeted metabolomics based on large-scale ms/ms data for elucidating metabolite accumulation patterns in plants.Plant and Cell Physiology,50(1):37-47
Shen YX,Cai XG,Gao ZH,2002.Studies on the chemical constituents of Shiraia bambusicola.China Journal of Chinese Materia Medica,27(9):674-677(in Chinese)
Srinivasan M,Sudheer AR,Menon VP,2007.Recent advances in Indian herbal drug research Guest Editor:Thomas Paul Asir Devasagayam ferulic acid:therapeutic potential through its antioxidant property.Journal of Clinical Biochemistry&Nutrition,40(2):92-100
Steinmeyer S,Lee K,Jayaraman A,Alaniz RC,2015.Microbiota metabolite regulation of host immune homeostasis:a mechanistic missing link.Current Allergy and Asthma Reports,15(5):524
Su MY,Niu JL,Li L,Yuan CG,Lu YH,2011.In vitro anti-tumor activity of nobiletin against five human cancer cell lines and its mechanism.Chinese Traditional Patent Medicine,2011(9):1479-1483(in Chinese)
Wang DD,Zhang LX,Huang XR,Wang X,Yang RN,Mao J,Wang XF,Wang XP,Zhang Q,Li P,2018.Identification of nutritional components in black sesame determined by widely targeted metabolomics and traditional Chinese medicines.Molecules,23:1180-1192
Wang X,Leung AW,Jiang Y,Yu H,Li X,Xu C,2012.Hypocrellin b-mediated sonodynamic action induces apoptosis of hepatocellular carcinoma cells.Ultrasonics,52(4):543-546
Xu GW,Lu X,Yang SL,2007.Recent advances in metabonomics.Acta Academiae Medicinae Sinicae,21(4):316-320(in Chinese)
Zhang Q,Zhao XH,Wang ZJ,2009.Cytotoxicity of flavones and flavonols to a human esophageal squamous cell carcinoma cell line(kyse-510)by induction of G2/Marrest and apoptosis.Toxicology in vitro,23(5):797-807
Zhao CG,Zhang LW,Wang H,Huang DY,2005.Study on anti-oxidation effects of cinnamic acid and its derivants.Food Science,26(1):218-222(in Chinese)
Zhao N,Chen SL,2018.Research progress on genetic diversity of Shiraia bambusicola,biosynthesis and anticancer activity of hypocrellin.Biotechnology Bulletin,34(4):16-23(in Chinese)
Zhenjun D,Lown JW,2010.Hypocrellins and their use in photosensitization.Photochemistry and Photobiology,52(3):609-616
Zou LQ,Wang CX,Kuang XJ,Li Y,Sun C,2016.Advance in flavonoids biosynthetic pathway and synthetic biology.China Journal of Chinese Material Medica,41(22):4124-4128(in Chinese)
陈占利,殷志琦,张健,叶文才,赵守训,2011.药用真菌竹黄的研究进展.亚太传统医药,7(7):160-163
方积年,叶淳渠,刘玉荣,1982.竹黄多糖的化学研究.化学学报,40(4):39-43
胡晓,沈联德,1992.竹黄化学成分的分离和结构鉴定.西药学杂志,7(1):1-4
贾小明,徐晓红,庄百川,林海萍,2006.药用竹黄菌的生物学研究进展.微生物学通报,33(3):147-150
梁晓辉,蔡宇杰,廖祥儒,魏兆媛,2008.药用真菌竹黄的研究进展.食品与生物技术学报,27(5):21-26
欧阳光察,薛应龙,1988.植物苯丙烷类代谢的生理意义及其调控.植物生理学通讯,1988(3):9-16
沈云修,菜先国,高宗华,2002.竹黄的化学成分研究.中国中药杂志,27(9):674-677
苏明媛,牛江龙,李林,袁才根,卢艳花,2011.川陈皮素的体外抑癌活性及其机制研究.中成药,2011(9):1479-1483
许国旺,路鑫,杨胜利,2007.代谢组学研究进展.中国医学科学院学报,29(6):701-711
赵春贵,张立伟,王晖,黄登宇,2005.肉桂酸及其衍生物抗氧化活性研究.食品科学,26(1):218-222
赵宁,陈双林,2018.竹黄遗传多样性与竹红菌素合成和抗癌作用的研究进展.生物技术通报,34(4):16-23
邹丽秋,王彩霞,匡雪君,李滢,孙超,2016.黄酮类化合物合成途径及合成生物学研究进展.中国中药杂志,41(22):4124-4128