Kavain (BioDeep_00000404666)

Main id: BioDeep_00000000061

 

natural product PANOMIX_OTCML-2023


代谢物信息卡片


NCGC00091905-05_C14H14O3_(6R)-4-Methoxy-6-[(E)-2-phenylvinyl]-5,6-dihydro-2H-pyran-2-one

化学式: C14H14O3 (230.0942894)
中文名称: 醉椒素, 醉椒素
谱图信息: 最多检出来源 Viridiplantae(plant) 7.14%

分子结构信息

SMILES: CO/C1=C/C(=O)O[C@H](C1)\C=C\C2=CC=CC=C2
InChI: InChI=1S/C14H14O3/c1-16-13-9-12(17-14(15)10-13)8-7-11-5-3-2-4-6-11/h2-8,10,12H,9H2,1H3/b8-7+

描述信息

D002492 - Central Nervous System Depressants > D014149 - Tranquilizing Agents > D014151 - Anti-Anxiety Agents
D002491 - Central Nervous System Agents > D011619 - Psychotropic Drugs > D014149 - Tranquilizing Agents
D002491 - Central Nervous System Agents > D002492 - Central Nervous System Depressants
D002491 - Central Nervous System Agents > D000927 - Anticonvulsants
Kawain is a member of 2-pyranones and an aromatic ether.
Kavain is a natural product found in Piper methysticum, Alnus sieboldiana, and Piper majusculum with data available.
See also: Piper methysticum root (part of).
(+)-Kavain, a main kavalactone extracted from Piper methysticum, has anticonvulsive properties, attenuating vascular smooth muscle contraction through interactions with voltage-dependent Na+ and Ca2+ channels[1]. (+)-Kavain is shown to bind at the α4β2δ GABAA receptor and potentiate GABA efficacy[2]. (+)-Kavain is used as a treatment for inflammatory diseases, its anti-inflammatory action has been widely studied[4].
(+)-Kavain, a main kavalactone extracted from Piper methysticum, has anticonvulsive properties, attenuating vascular smooth muscle contraction through interactions with voltage-dependent Na+ and Ca2+ channels[1]. (+)-Kavain is shown to bind at the α4β2δ GABAA receptor and potentiate GABA efficacy[2]. (+)-Kavain is used as a treatment for inflammatory diseases, its anti-inflammatory action has been widely studied[4].
(+)-Kavain, a main kavalactone extracted from Piper methysticum, has anticonvulsive properties, attenuating vascular smooth muscle contraction through interactions with voltage-dependent Na+ and Ca2+ channels[1]. (+)-Kavain is shown to bind at the α4β2δ GABAA receptor and potentiate GABA efficacy[2]. (+)-Kavain is used as a treatment for inflammatory diseases, its anti-inflammatory action has been widely studied[4].
(+)-Kavain, a main kavalactone extracted from Piper methysticum, has anticonvulsive properties, attenuating vascular smooth muscle contraction through interactions with voltage-dependent Na+ and Ca2+ channels[1]. (+)-Kavain is shown to bind at the α4β2δ GABAA receptor and potentiate GABA efficacy[2]. (+)-Kavain is used as a treatment for inflammatory diseases, its anti-inflammatory action has been widely studied[4].
(+)-Kavain, a main kavalactone extracted from Piper methysticum, has anticonvulsive properties, attenuating vascular smooth muscle contraction through interactions with voltage-dependent Na+ and Ca2+ channels[1]. (+)-Kavain is shown to bind at the α4β2δ GABAA receptor and potentiate GABA efficacy[2]. (+)-Kavain is used as a treatment for inflammatory diseases, its anti-inflammatory action has been widely studied[4].
(+)-Kavain, a main kavalactone extracted from Piper methysticum, has anticonvulsive properties, attenuating vascular smooth muscle contraction through interactions with voltage-dependent Na+ and Ca2+ channels[1]. (+)-Kavain is shown to bind at the α4β2δ GABAA receptor and potentiate GABA efficacy[2]. (+)-Kavain is used as a treatment for inflammatory diseases, its anti-inflammatory action has been widely studied[4].
Kavain is a class of kavalactone isolated from Piper methysticum, which has anxiolytic properties in animals and humans. Kavain positively modulated γ-Aminobutyric acid type A (GABAA) receptor[1].
Kavain is a class of kavalactone isolated from Piper methysticum, which has anxiolytic properties in animals and humans. Kavain positively modulated γ-Aminobutyric acid type A (GABAA) receptor[1].
Kavain is a class of kavalactone isolated from Piper methysticum, which has anxiolytic properties in animals and humans. Kavain positively modulated γ-Aminobutyric acid type A (GABAA) receptor[1].

同义名列表

49 个代谢物同义名

Neuronica; Kavain; 2H-PYRAN-2-ONE, 5,6-DIHYDRO-4-METHOXY-6-((1E)-2-PHENYLETHENYL)-, (6R)-; 2H-Pyran-2-one, 5,6-dihydro-4-methoxy-6-(2-phenylethenyl)-, (R-(E))-; 2H-Pyran-2-one, 5,6-dihydro-4-methoxy-6-(2-phenylethenyl)-, [R-(E)]-; 2,6-Heptadienoic acid, 5-hydroxy-3-methoxy-7-phenyl-, delta-lactone; 2H-Pyran-2-one,6-dihydro-4-methoxy-6-(2-phenylethenyl)-, [R-(E)]-; 5-Hydroxy-3-methoxy-7-phenyl-2,6-heptadienoic acid gamma-lactone; (6R)-4-methoxy-6-[(E)-2-phenylvinyl]-5,6-dihydro-2H-pyran-2-one; 4-Methoxy-6-(beta-phenylvinyl)-5,6-dihydro-alpha-pyrone; (R-(E))-5,6-Dihydro-4-methoxy-6-styryl-2H-pyran-2-one; 2H-Pyran-2-one, 5,6-dihydro-4-methoxy-6-styryl-, (+)-; 2H-PYRAN-2-ONE, 5,6-DIHYDRO-4-METHOXY-6-STYRYL-, (R)-; (2R)-4-methoxy-2-[(E)-styryl]-2,3-dihydropyran-6-one; (R,E)-4-methoxy-6-styryl-5,6-dihydro-2H-pyran-2-one; 2H-Pyran-2-one,6-dihydro-4-methoxy-6-styryl-, (+)-; 2H-Pyran-2-one,6-dihydro-4-methoxy-6-styryl-, (R)-; (R)-5,6-Dihydro-4-methoxy-6-styryl-2H-pyran-2-one; 2H-Pyran-2-one, 5,6-dihydro-4-methoxy-6-styryl-; XEAQIWGXBXCYFX-GUOLPTJISA-N; kavain, (E)-(+-)-isomer; kavain, (R)-(E)-isomer; kavain, (+-)-isomer; kavain, (R)-isomer; Prestwick3_000207; Prestwick2_000207; KAWAIN [USP-RS]; KAWAIN [WHO-DD]; UNII-W1ES06373M; KAWAIN (USP-RS); (R)-(+)-Kavain; BPBio1_000213; Kavaform (TN); Tox21_200907; KAWAIN [MI]; Kavain, dl-; W1ES06373M; (+)-Kavain; (+)-KAWAIN; Neuronika; D-Kawain; L-Kawain; kavaine; Gonosan; kawain; Kawaih; cavain; DL-Kavain; NCGC00091905-05_C14H14O3_(6R)-4-Methoxy-6-[(E)-2-phenylvinyl]-5,6-dihydro-2H-pyran-2-one



数据库引用编号

38 个数据库交叉引用编号

分类词条

相关代谢途径

Reactome(0)

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PlantCyc(0)

代谢反应

0 个相关的代谢反应过程信息。

Reactome(0)

BioCyc(0)

WikiPathways(0)

Plant Reactome(0)

INOH(0)

PlantCyc(0)

COVID-19 Disease Map(0)

PathBank(0)

PharmGKB(0)

在这里通过桑基图来展示出与当前的这个代谢物在我们的BioDeep知识库中具有相关联信息的其他代谢物。在这里进行关联的信息来源主要有：

  • PubMed: 来源于PubMed文献库中的文献信息，我们通过自然语言数据挖掘得到的在同一篇文献中被同时提及的相关代谢物列表，这个列表按照代谢物同时出现的文献数量降序排序，取前10个代谢物作为相关研究中关联性很高的代谢物集合展示在桑基图中。
  • NCBI Taxonomy: 通过文献数据挖掘，得到的代谢物物种来源信息关联。这个关联信息同样按照出现的次数降序排序，取前10个代谢物作为高关联度的代谢物集合展示在桑吉图上。
  • Chemical Taxonomy: 在物质分类上处于同一个分类集合中的其他代谢物
  • Chemical Reaction: 在化学反应过程中，存在为当前代谢物相关联的生化反应过程中的反应底物或者反应产物的关联代谢物信息。

点击图上的相关代谢物的名称，可以跳转到相关代谢物的信息页面。



文献列表

  • Adam Yasgar, Danielle Bougie, Richard T Eastman, Ruili Huang, Misha Itkin, Jennifer Kouznetsova, Caitlin Lynch, Crystal McKnight, Mitch Miller, Deborah K Ngan, Tyler Peryea, Pranav Shah, Paul Shinn, Menghang Xia, Xin Xu, Alexey V Zakharov, Anton Simeonov. Quantitative Bioactivity Signatures of Dietary Supplements and Natural Products. ACS pharmacology & translational science. 2023 May; 6(5):683-701. doi: 10.1021/acsptsci.2c00194. [PMID: 37200814]
  • Zhongbo Liu, Liankun Song, Jun Xie, Xue-Ru Wu, Greg E Gin, Beverly Wang, Edward Uchio, Xiaolin Zi. Kavalactone Kawain Impedes Urothelial Tumorigenesis in UPII-Mutant Ha-Ras Mice via Inhibition of mTOR Signaling and Alteration of Cancer Metabolism. Molecules (Basel, Switzerland). 2023 Feb; 28(4):. doi: 10.3390/molecules28041666. [PMID: 36838656]
  • Rafael Rocha da Silva Santos, Matheus Corrêa Ramos, Juliana Veloso Ferreira, José Eduardo Gonçalves, Isabela Costa César. Biopharmaceutical evaluation of kavain in Piper methysticum G. Forst dried extract: Equilibrium solubility and intestinal permeability in Caco-2 cell model. Journal of ethnopharmacology. 2022 Oct; 296(?):115480. doi: 10.1016/j.jep.2022.115480. [PMID: 35716919]
  • Juliana Veloso Ferreira, Isabella Campolina Pierotte, Felipe Fernandes Rodrigues, Larissa Camila Ribeiro de Souza, Rafael Wesley Bastos, Paulo Henrique Fonseca Carmo, Geovanni Dantas Cassali, Carlos Alberto Tagliati, Renes Resende Machado, Daniel Assis Santos, Gerson Antônio Pianetti, Isabela Costa César. Acute oral toxicity, antinociceptive and antimicrobial activities of kava dried extracts and synthetic kavain. Natural product research. 2022 Aug; 36(16):4221-4226. doi: 10.1080/14786419.2021.1973459. [PMID: 34491148]
  • Erasmo P DO Vale Junior, Marcos Vitor R Ferreira, Bianca Cristina S Fernandes, Thais T DA Silva, Francielle Alline Martins, Pedro Marcos DE Almeida. Protective effect of kavain in meristematic cells of Allium cepa L. Anais da Academia Brasileira de Ciencias. 2022; 94(2):e20200520. doi: 10.1590/0001-3765202220200520. [PMID: 35703688]
  • Xiaojun Zhao, Chao Su, Ruru Ren, Bo Zhang, Yingli Wang, Xiaojuan Su, Fangfang Lu, Rong Zong, Lingling Yang, Wannian Zhang, Xueqin Ma. Simultaneous determination of both kavalactone and flavokawain constituents by different single-marker methods in kava. Journal of separation science. 2021 Jul; 44(14):2705-2716. doi: 10.1002/jssc.202100198. [PMID: 33951745]
  • Agnès Barnabé, Yves Moulard, Stephane Trevisiol, Sophie Boyer, Mylène Caroff, Wafek Taleb, Sophie Tendon, Laura Drif, Vivian Delcourt, Marie-Agnès Popot, Ludovic Bailly-Chouriberry. Kavain detection in post-race equine urine sample: A case report. Drug testing and analysis. 2021 Apr; 13(4):883-886. doi: 10.1002/dta.2996. [PMID: 33496057]
  • Antonio Celentano, Callisthenis Yiannis, Rita Paolini, Pangzhen Zhang, Camile S Farah, Nicola Cirillo, Tami Yap, Michael McCullough. Kava constituents exert selective anticancer effects in oral squamous cell carcinoma cells in vitro. Scientific reports. 2020 09; 10(1):15904. doi: 10.1038/s41598-020-73058-4. [PMID: 32985597]
  • Juliana Veloso Ferreira, Alysson Vinícius Braga, Renes de Resende Machado, Deborah Michel, Gerson Antônio Pianetti, Anas El-Aneed, Isabela Costa César. Liquid chromatography-tandem mass spectrometry bioanalytical method for the determination of kavain in mice plasma: Application to a pharmacokinetic study. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2020 Jan; 1137(?):121939. doi: 10.1016/j.jchromb.2019.121939. [PMID: 31877429]
  • Pengcheng Wang, Junjie Zhu, Amina I Shehu, Jie Lu, Jing Chen, Xiao-Bo Zhong, Xiaochao Ma. Enzymes and Pathways of Kavain Bioactivation and Biotransformation. Chemical research in toxicology. 2019 07; 32(7):1335-1342. doi: 10.1021/acs.chemrestox.9b00098. [PMID: 31265262]
  • Ying Liu, Jensen A Lund, Susan J Murch, Paula N Brown. Single-Lab Validation for Determination of Kavalactones and Flavokavains in Piper methysticum (Kava). Planta medica. 2018 Nov; 84(16):1213-1218. doi: 10.1055/a-0637-2400. [PMID: 29940660]
  • Qiang Guo, Zhen Cao, Bo Wu, Fangxiao Chen, Jennifer Tickner, Ziyi Wang, Heng Qiu, Chao Wang, Kai Chen, Renxiang Tan, Qile Gao, Jiake Xu. Modulating calcium-mediated NFATc1 and mitogen-activated protein kinase deactivation underlies the inhibitory effects of kavain on osteoclastogenesis and bone resorption. Journal of cellular physiology. 2018 01; 234(1):789-801. doi: 10.1002/jcp.26893. [PMID: 30078210]
  • Adele Murauer, Markus Ganzera. Quantitative Determination of Lactones in Piper methysticum (Kava-Kava) by Supercritical Fluid Chromatography. Planta medica. 2017 Aug; 83(12-13):1053-1057. doi: 10.1055/s-0043-100632. [PMID: 28095587]
  • Xiaoren Tang, Salomon Amar. Kavain Involvement in LPS-Induced Signaling Pathways. Journal of cellular biochemistry. 2016 10; 117(10):2272-80. doi: 10.1002/jcb.25525. [PMID: 26917453]
  • Han Chow Chua, Emilie T H Christensen, Kirsten Hoestgaard-Jensen, Leonny Y Hartiadi, Iqbal Ramzan, Anders A Jensen, Nathan L Absalom, Mary Chebib. Kavain, the Major Constituent of the Anxiolytic Kava Extract, Potentiates GABAA Receptors: Functional Characteristics and Molecular Mechanism. PloS one. 2016; 11(6):e0157700. doi: 10.1371/journal.pone.0157700. [PMID: 27332705]
  • Atul Upadhyay, Emmy Tuenter, Rizwan Ahmad, Adnan Amin, Vasiliki Exarchou, Sandra Apers, Nina Hermans, Luc Pieters. Kavalactones, a novel class of protein glycation and lipid peroxidation inhibitors. Planta medica. 2014 Aug; 80(12):1001-8. doi: 10.1055/s-0034-1382949. [PMID: 25098935]
  • Yuma Iwai, Kouki Murakami, Yasuyuki Gomi, Toshihiro Hashimoto, Yoshinori Asakawa, Yoshinobu Okuno, Toyokazu Ishikawa, Dai Hatakeyama, Noriko Echigo, Takashi Kuzuhara. Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. PloS one. 2011; 6(5):e19825. doi: 10.1371/journal.pone.0019825. [PMID: 21625478]
  • Valerie Robinson, Wilma F Bergfeld, Donald V Belsito, Curtis D Klaassen, James G Marks, Ronald C Shank, Thomas J Slaga, Paul W Snyder, F Alan Andersen. Final report on the safety assessment of Piper methysticum leaf/root/stem extract and Piper methysticum root extract. International journal of toxicology. 2009 Nov; 28(6 Suppl):175S-88S. doi: 10.1177/1091581809350934. [PMID: 19966149]
  • Michael P Pollastri, Adrian Whitty, Jamie Cassidy Merrill, Xiaoren Tang, Trent D Ashton, Salomon Amar. Identification and characterization of kava-derived compounds mediating TNF-alpha suppression. Chemical biology & drug design. 2009 Aug; 74(2):121-8. doi: 10.1111/j.1747-0285.2009.00838.x. [PMID: 19538508]
  • A Matthias, J T Blanchfield, K G Penman, K M Bone, I Toth, R P Lehmann. Permeability studies of Kavalactones using a Caco-2 cell monolayer model. Journal of clinical pharmacy and therapeutics. 2007 Jun; 32(3):233-9. doi: 10.1111/j.1365-2710.2007.00810.x. [PMID: 17489874]
  • H Droege. [Acute hepatitis due to kava-kava and St John's Wort: an immune-mediated mechanism?]. Deutsche medizinische Wochenschrift (1946). 2006 Aug; 131(34-35):1882; author reply 1882-3. doi: 10.1055/s-2006-949178. [PMID: 16915556]
  • T D Xuan, A A Elzaawely, M Fukuta, S Tawata. Herbicidal and Fungicidal Activities of Lactones in Kava (Piper methysticum). Journal of agricultural and food chemistry. 2006 Feb; 54(3):720-5. doi: 10.1021/jf0519461. [PMID: 16448174]
  • J Anke, S Fu, I Ramzan. Kavalactones fail to inhibit alcohol dehydrogenase in vitro. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2006 Feb; 13(3):192-5. doi: 10.1016/j.phymed.2004.07.005. [PMID: 16428028]
  • Johanna Weiss, Alexandra Sauer, Andreas Frank, Matthias Unger. Extracts and kavalactones of Piper methysticum G. Forst (kava-kava) inhibit P-glycoprotein in vitro. Drug metabolism and disposition: the biological fate of chemicals. 2005 Nov; 33(11):1580-3. doi: 10.1124/dmd.105.005892. [PMID: 16051732]
  • James M Mathews, Amy S Etheridge, John L Valentine, Sherry R Black, Donna P Coleman, Purvi Patel, James So, Leo T Burka. Pharmacokinetics and disposition of the kavalactone kawain: interaction with kava extract and kavalactones in vivo and in vitro. Drug metabolism and disposition: the biological fate of chemicals. 2005 Oct; 33(10):1555-63. doi: 10.1124/dmd.105.004317. [PMID: 16033948]
  • Orapin Chienthavorn, Roger M Smith, Ian D Wilson, Brian Wright, Eva M Lenz. Superheated water chromatography-nuclear magnetic resonance spectroscopy of kava lactones. Phytochemical analysis : PCA. 2005 May; 16(3):217-21. doi: 10.1002/pca.848. [PMID: 15997856]
  • Lihong Hu, Jin-Woo Jhoo, Catharina Y W Ang, Michael Dinovi, Antonia Mattia. Determination of six kavalactones in dietary supplements and selected functional foods containing Piper methysticum by isocratic liquid chromatography with internal standard. Journal of AOAC International. 2005 Jan; 88(1):16-25. doi: . [PMID: 15759721]
  • Peter A Whitton, Andrew Lau, Alicia Salisbury, Julie Whitehouse, Christine S Evans. Kava lactones and the kava-kava controversy. Phytochemistry. 2003 Oct; 64(3):673-9. doi: 10.1016/s0031-9422(03)00381-9. [PMID: 13679089]
  • F Tarbah, H Mahler, B Kardel, W Weinmann, D Hafner, Th Daldrup. Kinetics of kavain and its metabolites after oral application. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2003 Jun; 789(1):115-30. doi: 10.1016/s1570-0232(03)00046-1. [PMID: 12726850]
  • Matthias Unger, Ulrike Holzgrabe, Wolfgang Jacobsen, Carolyn Cummins, Leslie Z Benet. Inhibition of cytochrome P450 3A4 by extracts and kavalactones of Piper methysticum (Kava-Kava). Planta medica. 2002 Dec; 68(12):1055-8. doi: 10.1055/s-2002-36360. [PMID: 12494328]
  • Hugh B Martin, Michael McCallum, William D Stofer, Mark R Eichinger. Kavain attenuates vascular contractility through inhibition of calcium channels. Planta medica. 2002 Sep; 68(9):784-9. doi: 10.1055/s-2002-34443. [PMID: 12357387]
  • Patrick J Mulholland, Mark A Prendergast. Post-insult exposure to (+/-) kavain potentiates N-methyl-D-aspartate toxicity in the developing hippocampus. Brain research. 2002 Jul; 945(1):106-13. doi: 10.1016/s0006-8993(02)02745-2. [PMID: 12113957]
  • Z Janeczko, J Krzek, N Pilewski, D Walusiak. Densitometric analysis of kawain in kava-kava root extracts. Acta poloniae pharmaceutica. 2001 Nov; 58(6):463-8. doi: . [PMID: 12197620]
  • L D Dinh, U Simmen, K B Bueter, B Bueter, K Lundstrom, W Schaffner. Interaction of various Piper methysticum cultivars with CNS receptors in vitro. Planta medica. 2001 Jun; 67(4):306-11. doi: 10.1055/s-2001-14334. [PMID: 11458444]
  • E A Abourashed, I A Khan. Microbial transformation of kawain and methysticin. Chemical & pharmaceutical bulletin. 2000 Dec; 48(12):1996-8. doi: 10.1248/cpb.48.1996. [PMID: 11145158]
  • M C Liao, H Arakaki, Y Li, A Takamiyagi, S Tawata, Y Aniya, H Sakurai, S Nonaka. Inhibitory effects of Alpinia speciosa K. SCHUM on the porphyrin photooxidative reaction. The Journal of dermatology. 2000 May; 27(5):312-7. doi: 10.1111/j.1346-8138.2000.tb02173.x. [PMID: 10875197]
  • S S Baum, R Hill, H Rommelspacher. Effect of kava extract and individual kavapyrones on neurotransmitter levels in the nucleus accumbens of rats. Progress in neuro-psychopharmacology & biological psychiatry. 1998 Oct; 22(7):1105-20. doi: 10.1016/s0278-5846(98)00062-1. [PMID: 9829291]
  • J M Langosch, C Normann, K Schirrmacher, M Berger, J Walden. The influence of (+/-)-kavain on population spikes and long-term potentiation in guinea pig hippocampal slices. Comparative biochemistry and physiology. Part A, Molecular & integrative physiology. 1998 Jul; 120(3):545-9. doi: 10.1016/s1095-6433(98)10064-8. [PMID: 9787833]
  • G Boonen, M A Beck, H Häberlein. Contribution to the quantitative and enantioselective determination of kavapyrones by high-performance liquid chromatography on ChiraSpher NT material. Journal of chromatography. B, Biomedical sciences and applications. 1997 Nov; 702(1-2):240-4. doi: 10.1016/s0378-4347(97)00389-7. [PMID: 9449578]
  • J Gleitz, A Beile, P Wilkens, A Ameri, T Peters. Antithrombotic action of the kava pyrone (+)-kavain prepared from Piper methysticum on human platelets. Planta medica. 1997 Feb; 63(1):27-30. doi: 10.1055/s-2006-957597. [PMID: 9063093]
  • E Holm, U Staedt, J Heep, C Kortsik, F Behne, A Kaske, I Mennicke. [The action profile of D,L-kavain. Cerebral sites and sleep-wakefulness-rhythm in animals]. Arzneimittel-Forschung. 1991 Jul; 41(7):673-83. doi: ". [PMID: 1772452]
  • C Köppel, J Tenczer. Mass spectral characterization of urinary metabolites of D,L-kawain. Journal of chromatography. 1991 Jan; 562(1-2):207-11. doi: 10.1016/0378-4347(91)80578-z. [PMID: 2026693]
  • D Lindenberg, H Pitule-Schödel. [D,L-kavain in comparison with oxazepam in anxiety disorders. A double-blind study of clinical effectiveness]. Fortschritte der Medizin. 1990 Jan; 108(2):49-50, 53. doi: . [PMID: 2179082]