甘草属植物中异戊烯基黄酮类成分及其药理活性研究进展
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摘要
异戊烯基黄酮类化合物是天然产物中一类极其重要的化合物,黄酮的异戊烯基化使其脂溶性和对生物膜的亲和力增加,肠道吸收能力增加继而提高生物利用度。通过查阅1968至2018年的文献,发现甘草属植物中的至少有105个黄酮类化合物具有异戊烯基取代,并在7种常见基本黄酮母核的A、B环均有分布。药理研究表明其具有抗炎、抗微生物、抗肿瘤等药理作用,其中尤以抗微生物活性更为显著。课题组对甘草属中的异戊烯基黄酮类化合物的结构特征及其生物活性进行总结,以期为相关中草药的临床研究和药物开发提供参考。
引文
[1] 刘洋洋,刘春生,曾斌芳,等.甘草种质资源研究进展[J].中草药,2013,44(24):3593-3598.
[2] 国家药典委员会.中华人民共和国药典:2015年版一部[S].北京:中国医药科技出版社,2015:86-87.
[3] 张雪辉,赵元芬,陈建民.甘草中总黄酮的含量测定[J].中国中药杂志,2001,26(11):746-796.
[4] Yang R,Wang L Q,Yuan B C,et al.The pharmacological activities of licorice[J].Planta Med,2015,81(18):1654-1669.
[5] Fukai T,Nishizawa J,Nomura T.Five isoprenoid-substituted flavonoids from Glycyrrhiza eurycarpa[J].Phytochemistry,1994,35(2):515-519.
[6] Li S,Li W,Wang Y,et al.Prenylflavonoids from Glycyrrhiza uralensis and their protein tyrosine phosphatase-1B inhibitory activities[J].Bioorg Med Chem Lett,2010,20(18):5398-401.
[7] Fukai T,Wang Q H,Takayama M,et al.Structures of five new prenylated flavonoids,gancaonins L,M,N,O,and P from aerial parts of Glycyrrhiza uralensis[J].Heterocycles,1990,31(2):373-382.
[8] 王青,苗文娟,向诚,等.乌拉尔甘草中黄酮类化学成分的研究[J].中草药,2014,45(1):31-36.
[9] Bai H,Li W,Koike K,et al.A new prenylated flavone from the leaves of Glycyrrhiza uralensis cultivated in China[J].Heterocycles,2004,63(9):2091-2095.
[10] Lin Y,Kuang Y,Li K,et al.Nrf2 activators from Glycyrrhiza inflata and their hepatoprotective activities against CCl4-induced liver injury in mice[J].Bioorg Med Chem Lett,2017,25(20):5522-5530.
[11] Mitscher L A,Rao G S R,Khanna I,et al.Antimicrobial agents from higher plants:prenylated flavonoids and other phenols from Glycyrrhiza lepidota[J].Phytochemistry,1983,22(2):573-576.
[12] Fukai T,Zeng L,Nishizawa J,et al.Four isoprenoid-substituted flavonoids from Glycyrrhiza aspera[J].Phytochemistry,1994,36(1):233-236.
[13] 贾世山,刘冬,郑秀萍,等.甘草叶中两个新异戊烯基黄酮类化合物[J].药学学报,1993,28(1):28-31.
[14] Fukai T,Wang Q H,Nomura T.Four new prenylated flavonoids from aerial parts of Glycyrrhiza uralensis[J].Heterocycles,1989,29(7):1369-1378.
[15] Li K,Ji S,Song W,et al.Glycybridins A-K,Bioactive phenolic compounds from Glycyrrhiza glabra[J].J Nat Prod,2017,80(2):334-346.
[16] Fukui H,Goto K,Tabata M.Two antimicrobial flavanones from the leaves of Glycyrrhiza glabra[J].Chem Pharm Bull,1988,36(10):4174-4176.
[17] Villinski J R,Bergeron C,Cannistra J C,et al.Pyrano-isoflavans from Glycyrrhiza uralensis with antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis[J].J Nat Prod,2014,77(3):521-526.
[18] Fukai T,Marumo A,Kaitou K,et al.Anti-helicobacter pylori flavonoids from licorice extract[J].Life Sci,2002,71(12):1449-1463.
[19] He J,Chen L,Heber D,et al.Antibacterial compounds from Glycyrrhiza uralensis[J].J Nat Prod,2006,69(1):121-124.
[20] Eerdunbayaer,Orabi M A,Aoyama H,et al.Structures of two new flavonoids and effects of licorice phenolics on vancomycin-resistant Enterococcus species[J].Molecules,2014,19(4):3883-3897.
[21] Fukai T,Nishizawa J,Nomura T.Variations in the chemical shift of the 5-hydroxyl proton of isoflavones;two isoflavones from licorice.[J].Phytochemistry,1994,36(1):225-228.
[22] Kuroda M,Mimaki Y,Honda S,et al.Phenolics from Glycyrrhiza glabra roots and their PPAR-γ ligand-binding activity[J].Bioorg Med Chem,2010,18(2):962-970.
[23] Lin Y,Kuang Y,Li K,et al.Screening for bioactive natural products from a 67-compound library of Glycyrrhiza inflata[J].Bioorg Med Chem,2017,25(14):3706-3713.
[24] Fukai T,Tantai L T.Isoprenoid-substituted flavonoids from Glycyrrhiza glabra[J].Phytochemistry,1996,43(2):531-532.
[25] Fukai T,Marumo A,Kaitou K,et al.Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus[J].Fitoterapia,2002,73(6):536-539.
[26] 张聿梅,许旭东,胡碧煌,等.黄甘草异黄酮成分的研究[J].药学学报,1997,32(4):301-304.
[27] Zeng L,Fukai T,Nomura T,et al.Four new prenylated flavonoids,glyasperins A,B,C,and D from the roots of Glycyrrhiza aspera[J].Heterocycles,1992,34(3):575-587.
[28] Fukai T,Nishizawa J,Yokoyama M,et al.Five new isoprenoid-substituted flavonoids,kanzonols F-J,from Glycyrrhiza uralensis[J].Heterocycles,1993,36(11):2565-2576.
[29] Hatano T,Shintani Y,Aga Y,et al.Phenolic constituents of licorice.Ⅷ.Structures of glicophenone and glicoisoflavanone,and effects of licorice phenolics on methicillin-resistant Staphylococcus aureus[J].Chem Pharm Bull,2000,48(9):1286-1292.
[30] Hatano T,Kagawa H,Yasuhara T,et al.Two new flavonoids and other constituents in licorice root:Their relative astringency and radical scavenging effects.[J].Chem Pharm Bull,1988,36(6):2090-2097.
[31] Saitoh T,Noguchi H,Shibata S,et al.Chemical studies on the Oriental plant drugs.XLIV.A new isoflavone and the corresponding isoflavanone of licorice root[J].Chem Pharm Bull,1978,26(1):144-147.
[32] Gafner S,Bergeron C,Villinski J R,et al.Isoflavonoids and Coumarins from Glycyrrhiza uralensis:antibacterial activity against oral pathogens and conversion of isoflavans into isoflavan-quinones during purification[J].J Nat Prod,2011,74(12):2514-2519.
[33] Zeng L,Fukai T,Nomura T,et al.Five new isoprenoid-substituted flavonoids,glyasperins F,G,H,I,and J from the roots of Glycyrrhiza aspera[J].Heterocycles,1992,34(9):1813-1828.
[34] Fukai T,Nomura T.Isoprenoid-substituted flavonoids from roots of Glycyrrhiza inflata[J].Phytochemistry,1995,38(3):759-765.
[35] Kirmizibekmez H,Uysal G B,Masullo M,et al.Prenylated polyphenolic compounds from Glycyrrhiza iconica and their antimicrobial and antioxidant activities[J].Fitoterapia,2015,103:289-293.
[36] Mitscher L A,Park Y H,Clark D.Antimicrobial agents from higher plants.Antimicrobial isoflavanoids and related substances from Glycyrrhiza glabra L.var.typica[J].J Nat Prod,1980,43(2):259.
[37] Fukai T,Wang Y H,Nishizawa J,et al.Three isoprenoid-substituted isoflavans,gancaonins X-Z,from Chinese folk medicine Tiexin Gancao (root xylems of Glycyrrhiza species)[J].Nat Med,1994,48(3):203-207.
[38] Fukai T,Nishizawa J,Yokoyama M,et al.Five new isoprenoid-substituted flavonoids,kanzonols M-P and R,from two Glycyrrhiza species[J].Heterocycles,1994,38(5):1089-1098.
[39] Dao T T,Nguyen P H,Lee H S,et al.Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata[J].Bioorg Med Chem Lett,2011,21(1):294-298.
[40] Chen J J,Cheng M J,Shu C W,et al.A new chalcone and antioxidant constituents of Glycyrrhiza glabra[J].Chem Nat Comp,2017,53(4):632-634.
[41] Fukai T,Wang Q H,Inami R,et al.Structures of prenylated dihydrochalcone,gancaonin J and homoisoflavanone,gancaonin K from Glycyrrhiza pallidiflora[J].Heterocycles,1990,31(4):643-650.
[42] Simmler C,Pauli G F,Chen S N.Phytochemistry and biological properties of glabridin[J].Fitoterapia,2013,90:160-184.
[43] Li J,Lim S S,Lee E S,et al.Isoangustone A suppresses mesangial fibrosis and inflammation in human renal mesangial cells[J].Exp Bio Med,2011,236(4):435-444.
[44] Cui Y,Ao M,Li W,et al.Anti-inflammatory activity of licochalcone a isolated from Glycyrrhiza inflata[J].Z Naturforsch,2008,63(5-6):361-365.
[45] Funakoshi-Tago M,Tanabe S,Tago K,et al.Licochalcone A potently inhibits tumor necrosis factor alpha-induced nuclear factor-κ B activation through the direct inhibition of Ⅰ κ B kinase complex activation[J].Mol Pharmacol,2009,76(4):745-753.
[46] Kolbe L,Immeyer J,Batzer J,et al.Anti-inflammatory efficacy of licochalcone A:correlation of clinical potency and in vitro effects[J].Arch Dermatol Res,2006,298(1):23-30.
[47] La V D,Tanabe S,Bergeron C,et al.Modulation of matrix metalloproteinase and cytokine production by licorice isolates licoricidin and licorisoflavan A:potential therapeutic approach for periodontitis[J].J Periodontol,2011,82(1):122-128.
[48] Park S H,Kang J S,Yoon Y D,et al.Glabridin inhibits lipopolysaccharide-induced activation of a microglial cell line,BV-2,by blocking NF-kappaB and AP-1[J].Phytother Res,2010,24:S29-S34.
[49] Elashmawy N E,Khedr N F,Elbahrawy H A,et al.Downregulation of iNOS and elevation of cAMP mediate the anti-inflammatory effect of glabridin in rats with ulcerative colitis[J].Inflammopharmacology,2018,26(2):551-559.
[50] Furusawa J,FunakoshiTago M,Mashino T,et al.Glycyrrhiza inflata-derived chalcones,licochalcone A,licochalcone B and licochalcone D,inhibit phosphorylation of NF-κB p65 in LPS signaling pathway[J].Int Immunopharmacol,2009,9(4):499-507.
[51] Shibata S,Inoue H,Iwata S,et al.Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice[J].Planta Med,1991,57(3):221-224.
[52] OkudaTanino A,Sugawara D,Tashiro T,et al.Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity[J].PLoS One,2017,12(3):e0173628.
[53] Kwon H S,Park J H,Kim D H,et al.Licochalcone a isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice[J].J Mol Med,2008,86(11):1287-1295.
[54] Jia T,Qiao J,Guan D,et al.Anti-inflammatory effects of licochalcone A on IL-1β-stimulated human osteoarthritis chondrocytes[J].Inflammation,2017,40(6):1894-1902.
[55] Hu J,Liu J.Licochalcone A attenuates lipopolysaccharide-induced acute kidney injury by inhibiting NF-κB activation[J].Inflammation,2016,39(2):569-574.
[56] Furuhashi I,Iwata S,Shibata S,et al.Inhibition by licochalcone A,a novel flavonoid isolated from liquorice root,of IL-1β-induced PGE2 production in human skin fibroblasts[J].J Pharm Pharmacol,2005,57(12):1661-1666.
[57] Chu X,Jiang L,Wei M,et al.Attenuation of allergic airway inflammation in a murine model of asthma by Licochalcone A[J].Immunopharm Immunot,2013,35(6):653-661.
[58] Chu X,Ci X,Wei M,et al.Licochalcone A inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo[J].J Agr Food Chem,2012,60(15):3947-3954.
[59] Franceschelli S,Pesce M,Ferrone A,et al.Biological effect of licochalcone C on the regulation of PI3K/Akt/eNOS and NF-κB/iNOS/NO signaling pathways in H9c2 cells in response to LPS stimulation[J].Int J Mol Sci,2017,18(4):690.
[60] Friismùller A,Chen M,Fuursted K,et al.In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots[J].Planta Med,2002,68(5):416-419.
[61] Tanaka Y,Kikuzaki H,Fukuda S,et al.Antibacterial compounds of licorice against upper airway respiratory tract pathogens[J].J Nutr Sci Vitaminol,2001,47(3):270.
[62] Adianti M,Aoki C,Komoto M,et al.Anti-hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species[J].Microbiol Immunol,2014,58(3):180-187.
[63] Grienke U,Braun H,Seidel N,et al.Computer-guided approach to access the anti-influenza activity of licorice constituents[J].J Nat Prod,2014,77(3):563-570.
[64] Kirmizibekmez H,Uysal G B,Masullo M,et al.Prenylated polyphenolic compounds from Glycyrrhiza iconica and their antimicrobial and antioxidant activities[J].Fitoterapia,2015,103:289-293.
[65] Tsukiyama R I,Katsura H,Tokuriki N,et al.Antibacterial activity of licochalcone A against spore-forming bacteria[J].Antimicrob Agents Ch,2002,46(5):1226-1230.
[66] Cho J J,Chae J I,Yoon G,et al.Licochalcone A,a natural chalconoid isolated from Glycyrrhiza inflata root,induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma[J].Int J Oncol,2014,45(2):667-674.
[67] Xue L,Zhang W J,Fan Q X,et al.Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells[J].Oncol lett,2018,15(2):1869-1873.
[68] Hsieh M J,Chen M K,Chen C J,et al.Glabridin induces apoptosis and autophagy through JNK1/2 pathway in human hepatoma cells[J].Phytomedicine,2016,23(4):359-366.
[69] Huang W,Tang S,Qiao X,et al.Isoangustone A induces apoptosis in SW480 human colorectal adenocarcinoma cells by disrupting mitochondrial functions[J].Fitoterapia,2014,94:36-47.
[70] Hsieh M J,Lin C W,Yang S F,et al.Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF-κB and AP-1 activity in human liver cancer cells[J].Brit J Pharmacol,2014,171(12):3037-3050.
[71] Huang H C,Tsai L L,Tsai J P,et al.Licochalcone A inhibits the migration and invasion of human lung cancer cells via inactivation of the Akt signaling pathway with downregulation of MMP-1/-3 expression[J].Tumor Biol,2014,35(12):12139-12149.
[72] Huang H L,Hsieh M J,Chien M H,et al.Glabridin mediate caspases activation and induces apoptosis through JNK1/2 and p38 MAPK pathway in human promyelocytic leukemia cells[J].PLoS One,2014,9(6):e98943.
[73] Garritano S,Pinto B,Giachi I,et al.Assessment of estrogenic activity of flavonoids from Mediterranean plants using an in vitro short-term test[J].Phytomedicine,2005,12(1-2):143-147.
[74] Chen X,Liu Z,Meng R,et al.Antioxidative and anticancer properties of licochalcone A from licorice[J].J Ethnopharmacol,2017,198:331-337.
[75] Kim H J,Seo J Y,Suh H J,et al.Antioxidant activities of licorice-derived prenylflavonoids[J].Nutr Res Pract,2012,6(6):491-498.
[76] 方诗琦,冷康,段金廒,等.甘草药渣中黄酮类成分及其抗氧化活性的研究[J].中成药,2015,37(11):2443-2448.
[77] Yuan X,Niu H,Wang P,et al.Cardioprotective effect of licochalcone D against myocardial ischemia/reperfusion injury in langendorff-perfused rat hearts[J].PLoS One,2015,10(6):e0128375.
[78] Huang B,Liu J,Ju C,et al.Licochalcone A prevents the loss of dopaminergic neurons by inhibiting microglial activation in lipopolysaccharide (LPS)-induced Parkinson′s disease models[J].Int J Mol Sci,2017,18(10):2043.
[79] Yoon G,Jung Y D,Cheon S H.Cytotoxic allyl retrochalcone from the roots of Glycyrrhiza inflata[J].Chem Pharm Bull,2005,53(6):694-695.
[80] Kim S,Kim J A,Lee S H,et al.In vitro inhibitory effect of licoricidin on human cytochrome P450s[J].Mass Spectrom Lett,2014,5(3):84-88.
[2] 国家药典委员会.中华人民共和国药典:2015年版一部[S].北京:中国医药科技出版社,2015:86-87.
[3] 张雪辉,赵元芬,陈建民.甘草中总黄酮的含量测定[J].中国中药杂志,2001,26(11):746-796.
[4] Yang R,Wang L Q,Yuan B C,et al.The pharmacological activities of licorice[J].Planta Med,2015,81(18):1654-1669.
[5] Fukai T,Nishizawa J,Nomura T.Five isoprenoid-substituted flavonoids from Glycyrrhiza eurycarpa[J].Phytochemistry,1994,35(2):515-519.
[6] Li S,Li W,Wang Y,et al.Prenylflavonoids from Glycyrrhiza uralensis and their protein tyrosine phosphatase-1B inhibitory activities[J].Bioorg Med Chem Lett,2010,20(18):5398-401.
[7] Fukai T,Wang Q H,Takayama M,et al.Structures of five new prenylated flavonoids,gancaonins L,M,N,O,and P from aerial parts of Glycyrrhiza uralensis[J].Heterocycles,1990,31(2):373-382.
[8] 王青,苗文娟,向诚,等.乌拉尔甘草中黄酮类化学成分的研究[J].中草药,2014,45(1):31-36.
[9] Bai H,Li W,Koike K,et al.A new prenylated flavone from the leaves of Glycyrrhiza uralensis cultivated in China[J].Heterocycles,2004,63(9):2091-2095.
[10] Lin Y,Kuang Y,Li K,et al.Nrf2 activators from Glycyrrhiza inflata and their hepatoprotective activities against CCl4-induced liver injury in mice[J].Bioorg Med Chem Lett,2017,25(20):5522-5530.
[11] Mitscher L A,Rao G S R,Khanna I,et al.Antimicrobial agents from higher plants:prenylated flavonoids and other phenols from Glycyrrhiza lepidota[J].Phytochemistry,1983,22(2):573-576.
[12] Fukai T,Zeng L,Nishizawa J,et al.Four isoprenoid-substituted flavonoids from Glycyrrhiza aspera[J].Phytochemistry,1994,36(1):233-236.
[13] 贾世山,刘冬,郑秀萍,等.甘草叶中两个新异戊烯基黄酮类化合物[J].药学学报,1993,28(1):28-31.
[14] Fukai T,Wang Q H,Nomura T.Four new prenylated flavonoids from aerial parts of Glycyrrhiza uralensis[J].Heterocycles,1989,29(7):1369-1378.
[15] Li K,Ji S,Song W,et al.Glycybridins A-K,Bioactive phenolic compounds from Glycyrrhiza glabra[J].J Nat Prod,2017,80(2):334-346.
[16] Fukui H,Goto K,Tabata M.Two antimicrobial flavanones from the leaves of Glycyrrhiza glabra[J].Chem Pharm Bull,1988,36(10):4174-4176.
[17] Villinski J R,Bergeron C,Cannistra J C,et al.Pyrano-isoflavans from Glycyrrhiza uralensis with antibacterial activity against Streptococcus mutans and Porphyromonas gingivalis[J].J Nat Prod,2014,77(3):521-526.
[18] Fukai T,Marumo A,Kaitou K,et al.Anti-helicobacter pylori flavonoids from licorice extract[J].Life Sci,2002,71(12):1449-1463.
[19] He J,Chen L,Heber D,et al.Antibacterial compounds from Glycyrrhiza uralensis[J].J Nat Prod,2006,69(1):121-124.
[20] Eerdunbayaer,Orabi M A,Aoyama H,et al.Structures of two new flavonoids and effects of licorice phenolics on vancomycin-resistant Enterococcus species[J].Molecules,2014,19(4):3883-3897.
[21] Fukai T,Nishizawa J,Nomura T.Variations in the chemical shift of the 5-hydroxyl proton of isoflavones;two isoflavones from licorice.[J].Phytochemistry,1994,36(1):225-228.
[22] Kuroda M,Mimaki Y,Honda S,et al.Phenolics from Glycyrrhiza glabra roots and their PPAR-γ ligand-binding activity[J].Bioorg Med Chem,2010,18(2):962-970.
[23] Lin Y,Kuang Y,Li K,et al.Screening for bioactive natural products from a 67-compound library of Glycyrrhiza inflata[J].Bioorg Med Chem,2017,25(14):3706-3713.
[24] Fukai T,Tantai L T.Isoprenoid-substituted flavonoids from Glycyrrhiza glabra[J].Phytochemistry,1996,43(2):531-532.
[25] Fukai T,Marumo A,Kaitou K,et al.Antimicrobial activity of licorice flavonoids against methicillin-resistant Staphylococcus aureus[J].Fitoterapia,2002,73(6):536-539.
[26] 张聿梅,许旭东,胡碧煌,等.黄甘草异黄酮成分的研究[J].药学学报,1997,32(4):301-304.
[27] Zeng L,Fukai T,Nomura T,et al.Four new prenylated flavonoids,glyasperins A,B,C,and D from the roots of Glycyrrhiza aspera[J].Heterocycles,1992,34(3):575-587.
[28] Fukai T,Nishizawa J,Yokoyama M,et al.Five new isoprenoid-substituted flavonoids,kanzonols F-J,from Glycyrrhiza uralensis[J].Heterocycles,1993,36(11):2565-2576.
[29] Hatano T,Shintani Y,Aga Y,et al.Phenolic constituents of licorice.Ⅷ.Structures of glicophenone and glicoisoflavanone,and effects of licorice phenolics on methicillin-resistant Staphylococcus aureus[J].Chem Pharm Bull,2000,48(9):1286-1292.
[30] Hatano T,Kagawa H,Yasuhara T,et al.Two new flavonoids and other constituents in licorice root:Their relative astringency and radical scavenging effects.[J].Chem Pharm Bull,1988,36(6):2090-2097.
[31] Saitoh T,Noguchi H,Shibata S,et al.Chemical studies on the Oriental plant drugs.XLIV.A new isoflavone and the corresponding isoflavanone of licorice root[J].Chem Pharm Bull,1978,26(1):144-147.
[32] Gafner S,Bergeron C,Villinski J R,et al.Isoflavonoids and Coumarins from Glycyrrhiza uralensis:antibacterial activity against oral pathogens and conversion of isoflavans into isoflavan-quinones during purification[J].J Nat Prod,2011,74(12):2514-2519.
[33] Zeng L,Fukai T,Nomura T,et al.Five new isoprenoid-substituted flavonoids,glyasperins F,G,H,I,and J from the roots of Glycyrrhiza aspera[J].Heterocycles,1992,34(9):1813-1828.
[34] Fukai T,Nomura T.Isoprenoid-substituted flavonoids from roots of Glycyrrhiza inflata[J].Phytochemistry,1995,38(3):759-765.
[35] Kirmizibekmez H,Uysal G B,Masullo M,et al.Prenylated polyphenolic compounds from Glycyrrhiza iconica and their antimicrobial and antioxidant activities[J].Fitoterapia,2015,103:289-293.
[36] Mitscher L A,Park Y H,Clark D.Antimicrobial agents from higher plants.Antimicrobial isoflavanoids and related substances from Glycyrrhiza glabra L.var.typica[J].J Nat Prod,1980,43(2):259.
[37] Fukai T,Wang Y H,Nishizawa J,et al.Three isoprenoid-substituted isoflavans,gancaonins X-Z,from Chinese folk medicine Tiexin Gancao (root xylems of Glycyrrhiza species)[J].Nat Med,1994,48(3):203-207.
[38] Fukai T,Nishizawa J,Yokoyama M,et al.Five new isoprenoid-substituted flavonoids,kanzonols M-P and R,from two Glycyrrhiza species[J].Heterocycles,1994,38(5):1089-1098.
[39] Dao T T,Nguyen P H,Lee H S,et al.Chalcones as novel influenza A (H1N1) neuraminidase inhibitors from Glycyrrhiza inflata[J].Bioorg Med Chem Lett,2011,21(1):294-298.
[40] Chen J J,Cheng M J,Shu C W,et al.A new chalcone and antioxidant constituents of Glycyrrhiza glabra[J].Chem Nat Comp,2017,53(4):632-634.
[41] Fukai T,Wang Q H,Inami R,et al.Structures of prenylated dihydrochalcone,gancaonin J and homoisoflavanone,gancaonin K from Glycyrrhiza pallidiflora[J].Heterocycles,1990,31(4):643-650.
[42] Simmler C,Pauli G F,Chen S N.Phytochemistry and biological properties of glabridin[J].Fitoterapia,2013,90:160-184.
[43] Li J,Lim S S,Lee E S,et al.Isoangustone A suppresses mesangial fibrosis and inflammation in human renal mesangial cells[J].Exp Bio Med,2011,236(4):435-444.
[44] Cui Y,Ao M,Li W,et al.Anti-inflammatory activity of licochalcone a isolated from Glycyrrhiza inflata[J].Z Naturforsch,2008,63(5-6):361-365.
[45] Funakoshi-Tago M,Tanabe S,Tago K,et al.Licochalcone A potently inhibits tumor necrosis factor alpha-induced nuclear factor-κ B activation through the direct inhibition of Ⅰ κ B kinase complex activation[J].Mol Pharmacol,2009,76(4):745-753.
[46] Kolbe L,Immeyer J,Batzer J,et al.Anti-inflammatory efficacy of licochalcone A:correlation of clinical potency and in vitro effects[J].Arch Dermatol Res,2006,298(1):23-30.
[47] La V D,Tanabe S,Bergeron C,et al.Modulation of matrix metalloproteinase and cytokine production by licorice isolates licoricidin and licorisoflavan A:potential therapeutic approach for periodontitis[J].J Periodontol,2011,82(1):122-128.
[48] Park S H,Kang J S,Yoon Y D,et al.Glabridin inhibits lipopolysaccharide-induced activation of a microglial cell line,BV-2,by blocking NF-kappaB and AP-1[J].Phytother Res,2010,24:S29-S34.
[49] Elashmawy N E,Khedr N F,Elbahrawy H A,et al.Downregulation of iNOS and elevation of cAMP mediate the anti-inflammatory effect of glabridin in rats with ulcerative colitis[J].Inflammopharmacology,2018,26(2):551-559.
[50] Furusawa J,FunakoshiTago M,Mashino T,et al.Glycyrrhiza inflata-derived chalcones,licochalcone A,licochalcone B and licochalcone D,inhibit phosphorylation of NF-κB p65 in LPS signaling pathway[J].Int Immunopharmacol,2009,9(4):499-507.
[51] Shibata S,Inoue H,Iwata S,et al.Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice[J].Planta Med,1991,57(3):221-224.
[52] OkudaTanino A,Sugawara D,Tashiro T,et al.Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity[J].PLoS One,2017,12(3):e0173628.
[53] Kwon H S,Park J H,Kim D H,et al.Licochalcone a isolated from licorice suppresses lipopolysaccharide-stimulated inflammatory reactions in RAW264.7 cells and endotoxin shock in mice[J].J Mol Med,2008,86(11):1287-1295.
[54] Jia T,Qiao J,Guan D,et al.Anti-inflammatory effects of licochalcone A on IL-1β-stimulated human osteoarthritis chondrocytes[J].Inflammation,2017,40(6):1894-1902.
[55] Hu J,Liu J.Licochalcone A attenuates lipopolysaccharide-induced acute kidney injury by inhibiting NF-κB activation[J].Inflammation,2016,39(2):569-574.
[56] Furuhashi I,Iwata S,Shibata S,et al.Inhibition by licochalcone A,a novel flavonoid isolated from liquorice root,of IL-1β-induced PGE2 production in human skin fibroblasts[J].J Pharm Pharmacol,2005,57(12):1661-1666.
[57] Chu X,Jiang L,Wei M,et al.Attenuation of allergic airway inflammation in a murine model of asthma by Licochalcone A[J].Immunopharm Immunot,2013,35(6):653-661.
[58] Chu X,Ci X,Wei M,et al.Licochalcone A inhibits lipopolysaccharide-induced inflammatory response in vitro and in vivo[J].J Agr Food Chem,2012,60(15):3947-3954.
[59] Franceschelli S,Pesce M,Ferrone A,et al.Biological effect of licochalcone C on the regulation of PI3K/Akt/eNOS and NF-κB/iNOS/NO signaling pathways in H9c2 cells in response to LPS stimulation[J].Int J Mol Sci,2017,18(4):690.
[60] Friismùller A,Chen M,Fuursted K,et al.In vitro antimycobacterial and antilegionella activity of licochalcone A from Chinese licorice roots[J].Planta Med,2002,68(5):416-419.
[61] Tanaka Y,Kikuzaki H,Fukuda S,et al.Antibacterial compounds of licorice against upper airway respiratory tract pathogens[J].J Nutr Sci Vitaminol,2001,47(3):270.
[62] Adianti M,Aoki C,Komoto M,et al.Anti-hepatitis C virus compounds obtained from Glycyrrhiza uralensis and other Glycyrrhiza species[J].Microbiol Immunol,2014,58(3):180-187.
[63] Grienke U,Braun H,Seidel N,et al.Computer-guided approach to access the anti-influenza activity of licorice constituents[J].J Nat Prod,2014,77(3):563-570.
[64] Kirmizibekmez H,Uysal G B,Masullo M,et al.Prenylated polyphenolic compounds from Glycyrrhiza iconica and their antimicrobial and antioxidant activities[J].Fitoterapia,2015,103:289-293.
[65] Tsukiyama R I,Katsura H,Tokuriki N,et al.Antibacterial activity of licochalcone A against spore-forming bacteria[J].Antimicrob Agents Ch,2002,46(5):1226-1230.
[66] Cho J J,Chae J I,Yoon G,et al.Licochalcone A,a natural chalconoid isolated from Glycyrrhiza inflata root,induces apoptosis via Sp1 and Sp1 regulatory proteins in oral squamous cell carcinoma[J].Int J Oncol,2014,45(2):667-674.
[67] Xue L,Zhang W J,Fan Q X,et al.Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells[J].Oncol lett,2018,15(2):1869-1873.
[68] Hsieh M J,Chen M K,Chen C J,et al.Glabridin induces apoptosis and autophagy through JNK1/2 pathway in human hepatoma cells[J].Phytomedicine,2016,23(4):359-366.
[69] Huang W,Tang S,Qiao X,et al.Isoangustone A induces apoptosis in SW480 human colorectal adenocarcinoma cells by disrupting mitochondrial functions[J].Fitoterapia,2014,94:36-47.
[70] Hsieh M J,Lin C W,Yang S F,et al.Glabridin inhibits migration and invasion by transcriptional inhibition of matrix metalloproteinase 9 through modulation of NF-κB and AP-1 activity in human liver cancer cells[J].Brit J Pharmacol,2014,171(12):3037-3050.
[71] Huang H C,Tsai L L,Tsai J P,et al.Licochalcone A inhibits the migration and invasion of human lung cancer cells via inactivation of the Akt signaling pathway with downregulation of MMP-1/-3 expression[J].Tumor Biol,2014,35(12):12139-12149.
[72] Huang H L,Hsieh M J,Chien M H,et al.Glabridin mediate caspases activation and induces apoptosis through JNK1/2 and p38 MAPK pathway in human promyelocytic leukemia cells[J].PLoS One,2014,9(6):e98943.
[73] Garritano S,Pinto B,Giachi I,et al.Assessment of estrogenic activity of flavonoids from Mediterranean plants using an in vitro short-term test[J].Phytomedicine,2005,12(1-2):143-147.
[74] Chen X,Liu Z,Meng R,et al.Antioxidative and anticancer properties of licochalcone A from licorice[J].J Ethnopharmacol,2017,198:331-337.
[75] Kim H J,Seo J Y,Suh H J,et al.Antioxidant activities of licorice-derived prenylflavonoids[J].Nutr Res Pract,2012,6(6):491-498.
[76] 方诗琦,冷康,段金廒,等.甘草药渣中黄酮类成分及其抗氧化活性的研究[J].中成药,2015,37(11):2443-2448.
[77] Yuan X,Niu H,Wang P,et al.Cardioprotective effect of licochalcone D against myocardial ischemia/reperfusion injury in langendorff-perfused rat hearts[J].PLoS One,2015,10(6):e0128375.
[78] Huang B,Liu J,Ju C,et al.Licochalcone A prevents the loss of dopaminergic neurons by inhibiting microglial activation in lipopolysaccharide (LPS)-induced Parkinson′s disease models[J].Int J Mol Sci,2017,18(10):2043.
[79] Yoon G,Jung Y D,Cheon S H.Cytotoxic allyl retrochalcone from the roots of Glycyrrhiza inflata[J].Chem Pharm Bull,2005,53(6):694-695.
[80] Kim S,Kim J A,Lee S H,et al.In vitro inhibitory effect of licoricidin on human cytochrome P450s[J].Mass Spectrom Lett,2014,5(3):84-88.