{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:36:28Z","timestamp":1785785788951,"version":"3.56.0"},"reference-count":118,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T00:00:00Z","timestamp":1479081600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T00:00:00Z","timestamp":1479081600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Multi-herb therapy has been widely used in Traditional Chinese medicine and tailored to meet the specific needs of each individual. However, the potential molecular or systems mechanisms of them to treat various diseases have not been fully elucidated. To address this question, a systems pharmacology approach, integrating pharmacokinetics, pharmacology and systems biology, is used to comprehensively identify the drug-target and drug-disease networks, exemplified by three representative <jats:italic>Radix Salviae Miltiorrhizae<\/jats:italic> herb pairs for treating various diseases (coronary heart disease, dysmenorrheal and nephrotic syndrome). First, the compounds evaluation and the multiple targeting technology screen the active ingredients and identify the specific targets for each herb of three pairs. Second, the herb feature mapping reveals the differences in chemistry and pharmacological synergy between pairs. Third, the constructed compound-target-disease network explains the mechanisms of treatment for various diseases from a systematic level. Finally, experimental verification is taken to confirm our strategy. Our work provides an integrated strategy for revealing the mechanism of synergistic herb pairs, and also a rational way for developing novel drug combinations for treatments of complex diseases.<\/jats:p>","DOI":"10.1038\/srep36985","type":"journal-article","created":{"date-parts":[[2016,11,14]],"date-time":"2016-11-14T10:06:53Z","timestamp":1479118013000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":58,"title":["Systems pharmacology exploration of botanic drug pairs reveals the mechanism for treating different diseases"],"prefix":"10.1038","volume":"6","author":[{"given":"Wei","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiping","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghua","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,11,14]]},"reference":[{"key":"BFsrep36985_CR1","first-page":"26","volume":"16","author":"XJ Li","year":"2008","unstructured":"Li, X. J. & Zhang, H. Y. Synergy in natural medicines: implications for drug discovery. Chin. J. Hematol 16, 26\u201328 (2008).","journal-title":"Chin. J. Hematol"},{"key":"BFsrep36985_CR2","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1021\/ci050135u","volume":"45","author":"H Li","year":"2005","unstructured":"Li, H. et al. Effect of selection of molecular descriptors on the prediction of blood-brain barrier penetrating and nonpenetrating agents by statistical learning methods. Journal of Chemical Information and Modeling 45, 1376\u20131384 (2005).","journal-title":"Journal of Chemical Information and Modeling"},{"key":"BFsrep36985_CR3","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1016\/j.drudis.2009.03.012","volume":"14","author":"X Ma","year":"2009","unstructured":"Ma, X. et al. Synergistic therapeutic actions of herbal ingredients and their mechanisms from molecular interaction and network perspectives. Drug discovery today 14, 579\u2013588 (2009).","journal-title":"Drug discovery today"},{"key":"BFsrep36985_CR4","unstructured":"Saiping, H. Pairings and taboos of commonly used Chinses herbs. Chinese Huasheng Pres (2012)."},{"key":"BFsrep36985_CR5","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/S0065-230X(08)60912-4","volume":"35","author":"MC Berenbaum","year":"1981","unstructured":"Berenbaum, M. C. Criteria for analyzing interactions between biologically active agents. Adv Cancer Res 35, 269\u2013335 (1981).","journal-title":"Adv Cancer Res"},{"key":"BFsrep36985_CR6","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1128\/AAC.46.9.2889-2894.2002","volume":"46","author":"J Wiesner","year":"2002","unstructured":"Wiesner, J., Henschker, D., Hutchinson, D. B., Beck, E. & Jomaa, H. In vitro and in vivo synergy of fosmidomycin, a novel antimalarial drug, with clindamycin. Antimicrobial Agents and Chemotherapy 46, 2889\u20132894 (2002).","journal-title":"Antimicrobial Agents and Chemotherapy"},{"key":"BFsrep36985_CR7","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1093\/toxsci\/kfs023","volume":"126","author":"EF Lock","year":"2012","unstructured":"Lock, E. F. et al. Quantitative high-throughput screening for chemical toxicity in a population-based in vitro model. Toxicological Sciences 126, 578\u2013588 (2012).","journal-title":"Toxicological Sciences"},{"key":"BFsrep36985_CR8","doi-asserted-by":"crossref","first-page":"5509","DOI":"10.1158\/1538-7445.AM10-5509","volume":"70","author":"RJ Rickles","year":"2010","unstructured":"Rickles, R. J. et al. Identification of synergistic drugs using combination high-throughput screening. Cancer Research 70, 5509\u20135509 (2010).","journal-title":"Cancer Research"},{"key":"BFsrep36985_CR9","doi-asserted-by":"crossref","first-page":"e1004975","DOI":"10.1371\/journal.pcbi.1004975","volume":"12","author":"X Chen","year":"2016","unstructured":"Chen, X. et al. NLLSS: Predicting Synergistic Drug Combinations Based on Semi-supervised Learning. PLoS Comput Biol 12, e1004975 (2016).","journal-title":"PLoS Comput Biol"},{"key":"BFsrep36985_CR10","doi-asserted-by":"crossref","unstructured":"Sun, X., Bao, J., You, Z., Chen, X. & Cui, J. Modeling of signaling crosstalk-mediated drug resistance and its implications on drug combination. Oncotarget, 11745 (2016).","DOI":"10.18632\/oncotarget.11745"},{"key":"BFsrep36985_CR11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1752-0509-5-1","volume":"5","author":"S Li","year":"2011","unstructured":"Li, S., Zhang, B. & Zhang, N. Network target for screening synergistic drug combinations with application to traditional Chinese medicine. BMC systems biology 5, 1 (2011).","journal-title":"BMC systems biology"},{"key":"BFsrep36985_CR12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1752-0509-4-1","volume":"4","author":"Z Wu","year":"2010","unstructured":"Wu, Z., Zhao, X. M. & Chen, L. A systems biology approach to identify effective cocktail drugs. BMC systems biology 4, 1 (2010).","journal-title":"BMC systems biology"},{"key":"BFsrep36985_CR13","doi-asserted-by":"crossref","unstructured":"Wang, X. et al. A systems biology approach to uncovering pharmacological synergy in herbal medicines with applications to cardiovascular disease. Evidence-Based Complementary and Alternative Medicine 2012 (2012).","DOI":"10.1155\/2012\/519031"},{"key":"BFsrep36985_CR14","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.jep.2013.09.018","volume":"150","author":"Y Yao","year":"2013","unstructured":"Yao, Y. et al. Deciphering the combination principles of Traditional Chinese Medicine from a systems pharmacology perspective based on Ma-huang Decoction. Journal of ethnopharmacology 150, 619\u2013638 (2013).","journal-title":"Journal of ethnopharmacology"},{"key":"BFsrep36985_CR15","first-page":"1","volume":"11","author":"S Li","year":"2010","unstructured":"Li, S., Zhang, B., Jiang, D., Wei, Y. & Zhang, N. Herb network construction and co-module analysis for uncovering the combination rule of traditional Chinese herbal formulae. BMC bioinformatics 11, 1 (2010).","journal-title":"BMC bioinformatics"},{"key":"BFsrep36985_CR16","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1007\/s11655-011-0853-5","volume":"17","author":"HZ Ye","year":"2011","unstructured":"Ye, H. Z., Zheng, C. S., Xu, X. J., Wu, M. X. & Liu, X. X. Potential synergistic and multitarget effect of herbal pair Chuanxiong Rhizome-Paeonia Albifora Pall on osteoarthritis disease: a computational pharmacology approach. Chinese journal of integrative medicine 17, 698\u2013703 (2011).","journal-title":"Chinese journal of integrative medicine"},{"key":"BFsrep36985_CR17","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.3892\/etm.2013.1291","volume":"6","author":"CS Zheng","year":"2013","unstructured":"Zheng, C. S. et al. Computational pharmacological comparison of Salvia miltiorrhiza and Panax notoginseng used in the therapy of cardiovascular diseases. Experimental and therapeutic medicine 6, 1163\u20131168 (2013).","journal-title":"Experimental and therapeutic medicine"},{"key":"BFsrep36985_CR18","doi-asserted-by":"crossref","unstructured":"Chen, X. et al. Drug\u2013target interaction prediction: databases, web servers and computational models. Briefings in bioinformatics bbv066 (2015).","DOI":"10.1093\/bib\/bbv066"},{"key":"BFsrep36985_CR19","doi-asserted-by":"crossref","first-page":"1970","DOI":"10.1039\/c2mb00002d","volume":"8","author":"X Chen","year":"2012","unstructured":"Chen, X., Liu, M. X. & Yan, G. Y. Drug\u2013target interaction prediction by random walk on the heterogeneous network. Molecular BioSystems 8, 1970\u20131978 (2012).","journal-title":"Molecular BioSystems"},{"key":"BFsrep36985_CR20","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1038\/msb.2008.60","volume":"4","author":"K Yang","year":"2008","unstructured":"Yang, K., Bai, H., Ouyang, Q., Lai, L. & Tang, C. Finding multiple target optimal intervention in disease\u2010related molecular network. Molecular Systems Biology 4, 228 (2008).","journal-title":"Molecular Systems Biology"},{"key":"BFsrep36985_CR21","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1126\/science.1158140","volume":"321","author":"M Campillos","year":"2008","unstructured":"Campillos, M., Kuhn, M., Gavin, A. C., Jensen, L. J. & Bork, P. Drug target identification using side-effect similarity. Science 321, 263\u2013266 (2008).","journal-title":"Science"},{"key":"BFsrep36985_CR22","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/msb.2011.26","volume":"7","author":"A Gottlieb","year":"2011","unstructured":"Gottlieb, A., Stein, G. Y., Ruppin, E. & Sharan, R. PREDICT: a method for inferring novel drug indications with application to personalized medicine. Molecular systems biology 7, 496 (2011).","journal-title":"Molecular systems biology"},{"key":"BFsrep36985_CR23","doi-asserted-by":"crossref","first-page":"e37608","DOI":"10.1371\/journal.pone.0037608","volume":"7","author":"H Yu","year":"2012","unstructured":"Yu, H. et al. A systematic prediction of multiple drug-target interactions from chemical, genomic, and pharmacological data. PloS one 7, e37608 (2012).","journal-title":"PloS one"},{"key":"BFsrep36985_CR24","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jep.2013.11.007","volume":"151","author":"W Zhou","year":"2014","unstructured":"Zhou, W. & Wang, Y. A network-based analysis of the types of coronary artery disease from traditional Chinese medicine perspective: potential for therapeutics and drug discovery. Journal of ethnopharmacology 151, 66\u201377 (2014).","journal-title":"Journal of ethnopharmacology"},{"key":"BFsrep36985_CR25","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1016\/j.jep.2013.02.004","volume":"146","author":"H Liu","year":"2013","unstructured":"Liu, H., Wang, J., Zhou, W., Wang, Y. & Yang, L. Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice. Journal of ethnopharmacology 146, 773\u2013793 (2013).","journal-title":"Journal of ethnopharmacology"},{"key":"BFsrep36985_CR26","doi-asserted-by":"crossref","unstructured":"Huang, C. et al. Systems pharmacology in drug discovery and therapeutic insight for herbal medicines. Briefings in bioinformatics bbt035 (2013).","DOI":"10.1093\/bib\/bbt035"},{"key":"BFsrep36985_CR27","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-6-13","volume":"6","author":"J Ru","year":"2014","unstructured":"Ru, J. et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. Journal of cheminformatics 6, 13 (2014).","journal-title":"Journal of cheminformatics"},{"key":"BFsrep36985_CR28","doi-asserted-by":"crossref","first-page":"6964","DOI":"10.3390\/ijms13066964","volume":"13","author":"X Xu","year":"2012","unstructured":"Xu, X. et al. A novel chemometric method for the prediction of human oral bioavailability. International journal of molecular sciences 13, 6964\u20136982 (2012).","journal-title":"International journal of molecular sciences"},{"key":"BFsrep36985_CR29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2012.09.051","volume":"145","author":"W Tao","year":"2013","unstructured":"Tao, W. et al. Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease. Journal of ethnopharmacology 145, 1\u201310 (2013).","journal-title":"Journal of ethnopharmacology"},{"key":"BFsrep36985_CR30","doi-asserted-by":"crossref","unstructured":"Madden, J. C. In silico approaches for predicting ADME properties. Recent advances in QSAR studies, 283\u2013304 (Springer, 2010).","DOI":"10.1007\/978-1-4020-9783-6_10"},{"key":"BFsrep36985_CR31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1472-6882-14-1","volume":"14","author":"H Yang","year":"2014","unstructured":"Yang, H. et al. A novel systems pharmacology model for herbal medicine injection: a case using reduning injection. BMC Complem Altern M 14, 1 (2014).","journal-title":"BMC Complem Altern M"},{"key":"BFsrep36985_CR32","doi-asserted-by":"crossref","first-page":"D1055","DOI":"10.1093\/nar\/gkq1165","volume":"39","author":"H Ye","year":"2011","unstructured":"Ye, H. et al. HIT: linking herbal active ingredients to targets. Nucleic acids research 39, D1055\u2013D1059 (2011).","journal-title":"Nucleic acids research"},{"key":"BFsrep36985_CR33","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/nar\/30.1.412","volume":"30","author":"X Chen","year":"2002","unstructured":"Chen, X., Ji, Z. L. & Chen, Y. Z. TTD: therapeutic target database. Nucleic acids research 30, 412\u2013415 (2002).","journal-title":"Nucleic acids research"},{"key":"BFsrep36985_CR34","doi-asserted-by":"crossref","first-page":"D1035","DOI":"10.1093\/nar\/gkq1126","volume":"39","author":"C Knox","year":"2011","unstructured":"Knox, C. et al. DrugBank 3.0: a comprehensive resource for \u2018omics\u2019 research on drugs. Nucleic acids research 39, D1035\u2013D1041 (2011).","journal-title":"Nucleic acids research"},{"key":"BFsrep36985_CR35","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nbt1284","volume":"25","author":"MJ Keiser","year":"2007","unstructured":"Keiser, M. J. et al. Relating protein pharmacology by ligand chemistry. Nature biotechnology 25, 197\u2013206 (2007).","journal-title":"Nature biotechnology"},{"key":"BFsrep36985_CR36","doi-asserted-by":"crossref","first-page":"D876","DOI":"10.1093\/nar\/gkr1011","volume":"40","author":"M Kuhn","year":"2012","unstructured":"Kuhn, M. et al. STITCH 3: zooming in on protein\u2013chemical interactions. Nucleic acids research 40, D876\u2013D880 (2012).","journal-title":"Nucleic acids research"},{"key":"BFsrep36985_CR37","doi-asserted-by":"crossref","first-page":"312","DOI":"10.2174\/138920307781369382","volume":"8","author":"RT Kroemer","year":"2007","unstructured":"Kroemer, R. T. Structure-based drug design: docking and scoring. Current Protein and Peptide Science 8, 312\u2013328 (2007).","journal-title":"Current Protein and Peptide Science"},{"key":"BFsrep36985_CR38","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/ng0407-426","volume":"39","author":"RB Altman","year":"2007","unstructured":"Altman, R. B. PharmGKB: a logical home for knowledge relating genotype to drug response phenotype. Nature genetics 39, 426 (2007).","journal-title":"Nature genetics"},{"key":"BFsrep36985_CR39","doi-asserted-by":"crossref","first-page":"D187","DOI":"10.1093\/nar\/gkj161","volume":"34","author":"CH Wu","year":"2006","unstructured":"Wu, C. H. et al. The Universal Protein Resource (UniProt): an expanding universe of protein information. Nucleic acids research 34, D187\u2013D191 (2006).","journal-title":"Nucleic acids research"},{"key":"BFsrep36985_CR40","doi-asserted-by":"crossref","first-page":"D1104","DOI":"10.1093\/nar\/gks994","volume":"41","author":"AP Davis","year":"2013","unstructured":"Davis, A. P. et al. The comparative toxicogenomics database: update 2013. Nucleic acids research 41, D1104\u2013D1114 (2013).","journal-title":"Nucleic acids research"},{"key":"BFsrep36985_CR41","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","volume":"19","author":"GM Morris","year":"1998","unstructured":"Morris, G. M. et al. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. Journal of computational chemistry 19, 1639\u20131662 (1998).","journal-title":"Journal of computational chemistry"},{"key":"BFsrep36985_CR42","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1517\/17460441.2010.484460","volume":"5","author":"S Cosconati","year":"2010","unstructured":"Cosconati, S. et al. Virtual screening with AutoDock: theory and practice. Expert Opinion on Drug Discovery 5, 597\u2013607 (2010).","journal-title":"Expert Opinion on Drug Discovery"},{"key":"BFsrep36985_CR43","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman, H. M. et al. The protein data bank. Nucleic acids research 28, 235\u2013242 (2000).","journal-title":"Nucleic acids research"},{"key":"BFsrep36985_CR44","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s11030-010-9262-5","volume":"15","author":"JL Medina-Franco","year":"2011","unstructured":"Medina-Franco, J. L., L\u00f3pez-Vallejo, F., Kuck, D. & Lyko, F. Natural products as DNA methyltransferase inhibitors: a computer-aided discovery approach. Molecular Diversity 15, 293\u2013304 (2011).","journal-title":"Molecular Diversity"},{"key":"BFsrep36985_CR45","doi-asserted-by":"crossref","first-page":"e43918","DOI":"10.1371\/journal.pone.0043918","volume":"7","author":"X Li","year":"2012","unstructured":"Li, X. et al. A system-level investigation into the mechanisms of Chinese Traditional Medicine: Compound Danshen Formula for cardiovascular disease treatment. PLoS One 7, e43918 (2012).","journal-title":"PLoS One"},{"key":"BFsrep36985_CR46","unstructured":"Case, D. et al. AMBER 10. University of California, San Francisco 32 (2008)."},{"key":"BFsrep36985_CR47","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1002\/jcc.10349","volume":"24","author":"Y Duan","year":"2003","unstructured":"Duan, Y. et al. A point\u2010charge force field for molecular mechanics simulations of proteins based on condensed\u2010phase quantum mechanical calculations. Journal of computational chemistry 24, 1999\u20132012 (2003).","journal-title":"Journal of computational chemistry"},{"key":"BFsrep36985_CR48","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1002\/jcc.10128","volume":"23","author":"A Jakalian","year":"2002","unstructured":"Jakalian, A., Jack, D. B. & Bayly, C. I. Fast, efficient generation of high\u2013quality atomic charges. AM1\u2010BCC model: II. Parameterization and validation. Journal of computational chemistry 23, 1623\u20131641 (2002).","journal-title":"Journal of computational chemistry"},{"key":"BFsrep36985_CR49","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","volume":"25","author":"J Wang","year":"2004","unstructured":"Wang, J., Wolf, R. M., Caldwell, J. W., Kollman, P. A. & Case, D. A. Development and testing of a general amber force field. Journal of computational chemistry 25, 1157\u20131174 (2004).","journal-title":"Journal of computational chemistry"},{"key":"BFsrep36985_CR50","doi-asserted-by":"crossref","first-page":"8345","DOI":"10.1063\/1.465608","volume":"99","author":"DM York","year":"1993","unstructured":"York, D. M., Darden, T. A. & Pedersen, L. G. The effect of long\u2013range electrostatic interactions in simulations of macromolecular crystals: a comparison of the Ewald and truncated list methods. The Journal of chemical physics 99, 8345\u20138348 (1993).","journal-title":"The Journal of chemical physics"},{"key":"BFsrep36985_CR51","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1023\/A:1008763014207","volume":"18","author":"I Massova","year":"2000","unstructured":"Massova, I. & Kollman, P. A. Combined molecular mechanical and continuum solvent approach (MM-PBSA\/GBSA) to predict ligand binding. Perspectives in Drug Discovery and Design 18, 113\u2013135 (2000).","journal-title":"Perspectives in Drug Discovery and Design"},{"key":"BFsrep36985_CR52","doi-asserted-by":"crossref","first-page":"6127","DOI":"10.1021\/ja00172a038","volume":"112","author":"WC Still","year":"1990","unstructured":"Still, W. C., Tempczyk, A., Hawley, R. C. & Hendrickson, T. Semianalytical treatment of solvation for molecular mechanics and dynamics. Journal of the American Chemical Society 112, 6127\u20136129 (1990).","journal-title":"Journal of the American Chemical Society"},{"key":"BFsrep36985_CR53","unstructured":"Gandhi, N. S. Molecular modelling of platelet endothelial cell adhesion molecule 1 and its interaction with glycosaminoglycans, Curtin University of Technology, School of Biomedical Sciences (2007)."},{"key":"BFsrep36985_CR54","unstructured":"Todeschini, R., Consonni, V., Mauri, A. & Pavan, M. DRAGON for windows (Software for Molecular Descriptor Calculations), version 5.4. TALETE srl, Milan (2006)."},{"key":"BFsrep36985_CR55","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","volume":"13","author":"P Shannon","year":"2003","unstructured":"Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome research 13, 2498\u20132504 (2003).","journal-title":"Genome research"},{"key":"BFsrep36985_CR56","unstructured":"Huimin, Y., Libei, H., Tong, S., Qiong, H. & Jinpu, L. Effects of replenishing Qi, promoting blood circulation and resolving phlegm on vascular endothelial function and blood coagulation system in senile patients with hyperlipemia. Journal of Traditional Chinese Medicine 26 (2006)."},{"key":"BFsrep36985_CR57","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1002\/ptr.2404","volume":"22","author":"XQ Yu","year":"2008","unstructured":"Yu, X. Q., Xue, C. C., Zhou, Z. W., Li, C. G. & Zhou, S. F. Tanshinone IIB, a primary active constituent from Salvia miltiorrhiza, exerts neuroprotective effect via inhibition of neuronal apoptosis in vitro. Phytotherapy Research 22, 846\u2013850 (2008).","journal-title":"Phytotherapy Research"},{"key":"BFsrep36985_CR58","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1055\/s-2006-961824","volume":"55","author":"A,FK Yaqi","year":"1989","unstructured":"Yaqi, A., F. K., Tanonaka, K., Hirai, K. & Takeo, S. Possible active components of tan-shen (Salvia miltiorrhiza) for protection of the myocardium against ischemia-induced derangements. Planta Med. 55, 51\u201354 (1989).","journal-title":"Planta Med"},{"key":"BFsrep36985_CR59","doi-asserted-by":"crossref","first-page":"237","DOI":"10.2174\/0929867053363397","volume":"12","author":"RW Jiang","year":"2005","unstructured":"Jiang, R. W. et al. Chemistry and biological activities of caffeic acid derivatives from Salvia miltiorrhiza. Current medicinal chemistry 12, 237\u2013246 (2005).","journal-title":"Current medicinal chemistry"},{"key":"BFsrep36985_CR60","first-page":"1171","volume":"38","author":"BL Zhao","year":"1996","unstructured":"Zhao, B. L., Jiang, W., Zhao, Y., Hou, J. W. & Xin, W. J. Scavenging effects of salvia miltiorrhiza on free radicals and its protection for myocardial mitochondrial membranes from ischemia-reperfusion injury. Biochemistry and molecular biology international 38, 1171\u20131182 (1996).","journal-title":"Biochemistry and molecular biology international"},{"key":"BFsrep36985_CR61","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/j.thromres.2006.06.008","volume":"119","author":"CS Shi","year":"2007","unstructured":"Shi, C. S. et al. Salvianolic acid B modulates hemostasis properties of human umbilical vein endothelial cells. Thrombosis research 119, 769\u2013775 (2007).","journal-title":"Thrombosis research"},{"key":"BFsrep36985_CR62","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.yjmcc.2006.03.007","volume":"41","author":"HS Zhang","year":"2006","unstructured":"Zhang, H. S. & Wang, S. Q. Salvianolic acid B from Salvia miltiorrhiza inhibits tumor necrosis factor-\u03b1 (TNF-\u03b1)-induced MMP-2 upregulation in human aortic smooth muscle cells via suppression of NAD (P) H oxidase-derived reactive oxygen species. Journal of molecular and cellular cardiology 41, 138\u2013148 (2006).","journal-title":"Journal of molecular and cellular cardiology"},{"key":"BFsrep36985_CR63","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijpharm.2006.07.003","volume":"326","author":"YT Wu","year":"2006","unstructured":"Wu, Y. T. et al. Bioavailability of salvianolic acid B in conscious and freely moving rats. International journal of pharmaceutics 326, 25\u201331 (2006).","journal-title":"International journal of pharmaceutics"},{"key":"BFsrep36985_CR64","unstructured":"Zhu, Y. P. Chinese Materia Medica: Chemistry, Pharmacology, and Applications. 273\u2013274 (Harwood Academic Publishers, 1998)."},{"key":"BFsrep36985_CR65","first-page":"1231","volume":"297","author":"YZ Zhu","year":"2002","unstructured":"Zhu, Y. Z. & Zhu, Y. C. Rediscovering remedies. Science 297, 1231 (2002).","journal-title":"Science"},{"key":"BFsrep36985_CR66","first-page":"578","volume":"59","author":"X Liu","year":"2007","unstructured":"Liu, X., Xin, H. & Zhu, Y. More than a \u201cmother-benefiting\u201d herb: cardioprotective effect of Herba leonuri. Acta Physiologica Sinica-Chinese Edition- 59, 578 (2007).","journal-title":"Acta Physiologica Sinica-Chinese Edition-"},{"key":"BFsrep36985_CR67","first-page":"051","volume":"21","author":"SY Liu","year":"2011","unstructured":"Liu, S. Y., Bai, M., JI, X. N., Zhang, Y. & Miao, M. S. Effect of Total Alkaloids Extracted from Leonuri Herba on Mice Benign Prostate Hyperplasia. Chinese Journal of Experimental Traditional Medical Formulae 21, 051 (2011).","journal-title":"Chinese Journal of Experimental Traditional Medical Formulae"},{"key":"BFsrep36985_CR68","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/S0024-3205(00)00987-5","volume":"68","author":"CX Chen","year":"2001","unstructured":"Chen, C. X. & Kwan, C. Y. Endothelium-independent vasorelaxation by leonurine, a plant alkaloid purified from Chinese motherwort. Life sciences 68, 953\u2013960 (2001).","journal-title":"Life sciences"},{"key":"BFsrep36985_CR69","doi-asserted-by":"crossref","first-page":"2661","DOI":"10.1161\/STROKEAHA.110.589895","volume":"41","author":"KP Loh","year":"2010","unstructured":"Loh, K. P. et al. Leonurine protects middle cerebral artery occluded rats through antioxidant effect and regulation of mitochondrial function. Stroke 41, 2661\u20132668 (2010).","journal-title":"Stroke"},{"key":"BFsrep36985_CR70","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1093\/ajcn\/74.4.418","volume":"74","author":"RJ Nijveldt","year":"2001","unstructured":"Nijveldt, R. J. et al. Flavonoids: a review of probable mechanisms of action and potential applications. The American journal of clinical nutrition 74, 418\u2013425 (2001).","journal-title":"The American journal of clinical nutrition"},{"key":"BFsrep36985_CR71","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1080\/10715760600823128","volume":"40","author":"F Perez-Vizcaino","year":"2006","unstructured":"Perez-Vizcaino, F., Duarte, J. & Andriantsitohaina, R. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols. Free radical research 40, 1054\u20131065 (2006).","journal-title":"Free radical research"},{"key":"BFsrep36985_CR72","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.jep.2003.09.042","volume":"90","author":"A Jagtap","year":"2004","unstructured":"Jagtap, A., Shirke, S. & Phadke, A. Effect of polyherbal formulation on experimental models of inflammatory bowel diseases. Journal of ethnopharmacology 90, 195\u2013204 (2004).","journal-title":"Journal of ethnopharmacology"},{"key":"BFsrep36985_CR73","doi-asserted-by":"crossref","first-page":"1667","DOI":"10.1055\/s-0028-1088314","volume":"74","author":"G Seelinger","year":"2008","unstructured":"Seelinger, G., Merfort, I. & Schempp, C. M. Anti-oxidant, anti-inflammatory and anti-allergic activities of luteolin. Planta medica 74, 1667\u20131677 (2008).","journal-title":"Planta medica"},{"key":"BFsrep36985_CR74","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-2008-1074919","volume":"39","author":"M Gupta","year":"1980","unstructured":"Gupta, M. et al. Anti-inflammatory and antipyretic activities of \u03b2-sitosterol. Planta medica 39, 157\u2013163 (1980).","journal-title":"Planta medica"},{"key":"BFsrep36985_CR75","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.cropro.2011.11.016","volume":"33","author":"M Kumar","year":"2012","unstructured":"Kumar, M., Das, T. & Yaduraju, N. An integrated approach for management of Cyperus rotundus (purple nutsedge) in soybean\u2013wheat cropping system. Crop protection 33, 74\u201381 (2012).","journal-title":"Crop protection"},{"key":"BFsrep36985_CR76","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.jep.2013.02.034","volume":"147","author":"SH Jung","year":"2013","unstructured":"Jung, S. H. et al. \u03b1-Cyperone, isolated from the rhizomes of Cyperus rotundus, inhibits LPS-induced COX-2 expression and PGE2 production through the negative regulation of NF\u03baB signalling in RAW 264.7 cells. Journal of ethnopharmacology 147, 208\u2013214 (2013).","journal-title":"Journal of ethnopharmacology"},{"key":"BFsrep36985_CR77","doi-asserted-by":"crossref","unstructured":"Kimura, T., But, P., Sung, C. & Han, B. International collation of traditional and folk medicine 13 (World Scientific, 1996).","DOI":"10.1142\/3041"},{"key":"BFsrep36985_CR78","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1007\/BF02980102","volume":"27","author":"ER Woo","year":"2004","unstructured":"Woo, E. R. & Piao, M. S. Antioxidative constituents fromlycopus lucidus. Archives of pharmacal research 27, 173\u2013176 (2004).","journal-title":"Archives of pharmacal research"},{"key":"BFsrep36985_CR79","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jep.2005.05.024","volume":"100","author":"J Liu","year":"2005","unstructured":"Liu, J. Oleanolic acid and ursolic acid: research perspectives. Journal of ethnopharmacology 100, 92\u201394 (2005).","journal-title":"Journal of ethnopharmacology"},{"key":"BFsrep36985_CR80","first-page":"523","volume":"134","author":"M Stacey","year":"1947","unstructured":"Stacey, M. & Webb, M. Studies on the antibacterial properties of the bile acids and some compounds derived from cholanic acid. Proceedings of the Royal Society of London. Series B-Biological Sciences 134, 523\u2013537 (1947).","journal-title":"Proceedings of the Royal Society of London. Series B-Biological Sciences"},{"key":"BFsrep36985_CR81","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0890-6238(99)00066-0","volume":"14","author":"M Ema","year":"2000","unstructured":"Ema, M., Miyawaki, E. & Kawashima, K. Effects of dibutyl phthalate on reproductive function in pregnant and pseudopregnant rats. Reproductive Toxicology 14, 13\u201319 (2000).","journal-title":"Reproductive Toxicology"},{"key":"BFsrep36985_CR82","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/prot.22047","volume":"73","author":"C Yan","year":"2008","unstructured":"Yan, C. et al. Comparative molecular dynamics simulations of histone deacetylase\u2010like protein: Binding modes and free energy analysis to hydroxamic acid inhibitors. Proteins: Structure, Function, and Bioinformatics 73, 134\u2013149 (2008).","journal-title":"Proteins: Structure, Function, and Bioinformatics"},{"key":"BFsrep36985_CR83","first-page":"130","volume":"7","author":"M Spinella","year":"2002","unstructured":"Spinella, M. The importance of pharmacological synergy in psychoactive herbal medicines. Alternative Medicine Review 7, 130\u2013137 (2002).","journal-title":"Alternative Medicine Review"},{"key":"BFsrep36985_CR84","doi-asserted-by":"crossref","unstructured":"Adams, J. D., Wang, R., Yang, J. & Lien, E. J. Preclinical and clinical examinations of Salvia miltiorrhiza and its tanshinones in ischemic conditions. Chin Med 1 (2006).","DOI":"10.1186\/1749-8546-1-3"},{"key":"BFsrep36985_CR85","first-page":"S64","volume":"38","author":"R Greger","year":"1992","unstructured":"Greger, R., Lohrmann, E. & Schlatter, E. Action of diuretics at the cellular level. Clinical nephrology 38, S64\u2013S68 (1992).","journal-title":"Clinical nephrology"},{"key":"BFsrep36985_CR86","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.ejphar.2006.05.010","volume":"541","author":"D Kondo","year":"2006","unstructured":"Kondo, D. et al. Progesterone receptor antagonist is effective in relieving neuropathic pain. European journal of pharmacology 541, 44\u201348 (2006).","journal-title":"European journal of pharmacology"},{"key":"BFsrep36985_CR87","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1161\/01.HYP.34.4.920","volume":"34","author":"JF Reckelhoff","year":"1999","unstructured":"Reckelhoff, J. F., Zhang, H., Srivastava, K. & Granger, J. P. Gender Differences in Hypertension in Spontaneously Hypertensive Rats Role of Androgens and Androgen Receptor. Hypertension 34, 920\u2013923 (1999).","journal-title":"Hypertension"},{"key":"BFsrep36985_CR88","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1186\/1752-0509-4-161","volume":"4","author":"C Luni","year":"2010","unstructured":"Luni, C., Shoemaker, J., Sanft, K., Petzold, L. & Doyle, F. Confidence from uncertainty-A multi-target drug screening method from robust control theory. BMC Systems Biology 4, 161 (2010).","journal-title":"BMC Systems Biology"},{"key":"BFsrep36985_CR89","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1016\/j.copbio.2010.05.004","volume":"21","author":"E Klipp","year":"2010","unstructured":"Klipp, E., Wade, R. C. & Kummer, U. Biochemical network-based drug-target prediction. Current opinion in biotechnology 21, 511\u2013516 (2010).","journal-title":"Current opinion in biotechnology"},{"key":"BFsrep36985_CR90","first-page":"60","volume":"23","author":"L Zhao","year":"2010","unstructured":"Zhao, L., Zhou, Y. L. & Wang X. P. Application study on Salvia Comparability with Chinese Medicine of Activating Blood Circulation and Eliminating Stasis. Gansu Journal of TCM 23, 60\u201361 (2010).","journal-title":"Gansu Journal of TCM"},{"key":"BFsrep36985_CR91","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1111\/j.1538-7836.2008.03169.x","volume":"6","author":"F Adam","year":"2008","unstructured":"Adam, F., Kauskot, A., Rosa, J. P. & Bryckaert, M. Mitogen-activated protein kinases in hemostasis and thrombosis. Journal of Thrombosis and Haemostasis 6, 2007\u20132016 (2008).","journal-title":"Journal of Thrombosis and Haemostasis"},{"key":"BFsrep36985_CR92","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/01.CCM.0000159563.97092.A7","volume":"33","author":"A Janvier","year":"2005","unstructured":"Janvier, A., Nadeau, S., Baribeau, J. & Perreault, T. Role of vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 in the vasodilator response to vascular endothelial growth factor in the neonatal piglet lung. Critical care medicine 33, 860\u2013866 (2005).","journal-title":"Critical care medicine"},{"key":"BFsrep36985_CR93","doi-asserted-by":"crossref","first-page":"H1592","DOI":"10.1152\/ajpheart.1998.275.5.H1592","volume":"275","author":"DG Johns","year":"1998","unstructured":"Johns, D. G. & Webb, R. C. TNF-\u03b1-induced endothelium-independent vasodilation: a role for phospholipase A2-dependent ceramide signaling. American Journal of Physiology-Heart and Circulatory Physiology 275, H1592\u2013H1598 (1998).","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"BFsrep36985_CR94","doi-asserted-by":"crossref","first-page":"e76","DOI":"10.1161\/01.CIR.101.6.e76","volume":"101","author":"M Verstraete","year":"2000","unstructured":"Verstraete, M. Synthetic inhibitors of platelet glycoprotein IIb\/IIIa in clinical development. Circulation 101, e76\u2013e80 (2000).","journal-title":"Circulation"},{"key":"BFsrep36985_CR95","first-page":"2556","volume":"55","author":"SL Kargman","year":"1995","unstructured":"Kargman, S. L. et al. Expression of prostaglandin G\/H synthase-1 and-2 protein in human colon cancer. Cancer research 55, 2556\u20132559 (1995).","journal-title":"Cancer research"},{"key":"BFsrep36985_CR96","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1177\/1559827609334518","volume":"3","author":"AS Leon","year":"2009","unstructured":"Leon, A. S. & Bronas, U. G. Dyslipidemia and risk of coronary heart disease: role of lifestyle approaches for its management. American Journal of Lifestyle Medicine 3, 257\u2013273 (2009).","journal-title":"American Journal of Lifestyle Medicine"},{"key":"BFsrep36985_CR97","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1210\/endo.141.9.7681","volume":"141","author":"SU Trost","year":"2000","unstructured":"Trost, S. U. et al. The thyroid hormone receptor-\u03b2-selective agonist GC-1 differentially affects plasma lipids and cardiac activity. Endocrinology 141, 3057\u20133064 (2000).","journal-title":"Endocrinology"},{"key":"BFsrep36985_CR98","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/clc.4960270510","volume":"27","author":"P Hallberg","year":"2004","unstructured":"Hallberg, P. et al. Gender\u2010specific association between preproendothelin\u20101 genotype and reduction of systolic blood pressure during antihypertensive treatment results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). Clinical cardiology 27, 287\u2013290 (2004).","journal-title":"Clinical cardiology"},{"key":"BFsrep36985_CR99","doi-asserted-by":"crossref","first-page":"11416","DOI":"10.3390\/ijms150711416","volume":"15","author":"J Li","year":"2014","unstructured":"Li, J. et al. The dipeptidyl peptidase-4 inhibitor sitagliptin protects against dyslipidemia-related kidney injury in Apolipoprotein E knockout mice. International journal of molecular sciences 15, 11416\u201311434 (2014).","journal-title":"International journal of molecular sciences"},{"key":"BFsrep36985_CR100","first-page":"1234","volume":"22","author":"T Kishi","year":"2008","unstructured":"Kishi, T., Hirooka, Y. & Sunagawa, K. Impaired neurogenesis and activated caspase 3-dependent apoptosis pathway in the rostral ventrolateral medulla cause hypertension in stroke-prone spontaneously hypertensive rats. Faseb J 22, 1234\u20135 (2008).","journal-title":"Faseb J"},{"key":"BFsrep36985_CR101","first-page":"e21","volume":"59","author":"SB Cau","year":"2012","unstructured":"Cau, S. B. & Tostes, R. C. Inducible Nitric Oxide Synthase Inhibition as a Target for the Treatment of Vascular Dysfunction in Hypertension. Hypertension 59, e21\u2013e21 (2012).","journal-title":"Hypertension"},{"key":"BFsrep36985_CR102","doi-asserted-by":"crossref","first-page":"538","DOI":"10.3109\/10641963.2011.566956","volume":"33","author":"X Zhou","year":"2011","unstructured":"Zhou, X. et al. Chronic antagonism of the mineralocorticoid receptor ameliorates hypertension and end organ damage in a rodent model of salt-sensitive hypertension. Clinical and experimental hypertension 33, 538\u2013547 (2011).","journal-title":"Clinical and experimental hypertension"},{"key":"BFsrep36985_CR103","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/S0735-1097(99)00600-2","volume":"35","author":"AM Feldman","year":"2000","unstructured":"Feldman, A. M. et al. The role of tumor necrosis factor in the pathophysiology of heart failure. Journal of the American College of Cardiology 35, 537\u2013544 (2000).","journal-title":"Journal of the American College of Cardiology"},{"key":"BFsrep36985_CR104","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1124\/jpet.111.184796","volume":"339","author":"C Liu","year":"2011","unstructured":"Liu, C. et al. Glucocorticoids improve renal responsiveness to atrial natriuretic peptide by up-regulating natriuretic peptide receptor-A expression in the renal inner medullary collecting duct in decompensated heart failure. Journal of Pharmacology and Experimental Therapeutics 339, 203\u2013209 (2011).","journal-title":"Journal of Pharmacology and Experimental Therapeutics"},{"key":"BFsrep36985_CR105","first-page":"487","volume":"23","author":"ME Ernst","year":"2010","unstructured":"Ernst, M. E. & Gordon, J. A. Diuretic therapy: key aspects in hypertension and renal disease. J Nephrol 23, 487\u2013493 (2010).","journal-title":"J Nephrol"},{"key":"BFsrep36985_CR106","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/0002-9378(78)90019-4","volume":"130","author":"O Ylikorkala","year":"1978","unstructured":"Ylikorkala, O. & Dawood, M. New concepts in dysmenorrhea. American Journal of Obstetrics and Gynecology 130, 833\u2013847 (1978).","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"BFsrep36985_CR107","doi-asserted-by":"crossref","first-page":"H2068","DOI":"10.1152\/ajpheart.00525.2009","volume":"297","author":"R Aamand","year":"2009","unstructured":"Aamand, R. et al. Generation of nitric oxide from nitrite by carbonic anhydrase: a possible link between metabolic activity and vasodilation. American Journal of Physiology-Heart and Circulatory Physiology 297, H2068\u2013H2074 (2009).","journal-title":"American Journal of Physiology-Heart and Circulatory Physiology"},{"key":"BFsrep36985_CR108","doi-asserted-by":"crossref","first-page":"7462","DOI":"10.1523\/JNEUROSCI.17-19-07462.1997","volume":"17","author":"AB Malmberg","year":"1997","unstructured":"Malmberg, A. B. et al. Diminished inflammation and nociceptive pain with preservation of neuropathic pain in mice with a targeted mutation of the type I regulatory subunit of cAMP-dependent protein kinase. The Journal of neuroscience 17, 7462\u20137470 (1997).","journal-title":"The Journal of neuroscience"},{"key":"BFsrep36985_CR109","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1016\/S0006-291X(03)00470-4","volume":"303","author":"T Tanioka","year":"2003","unstructured":"Tanioka, T. et al. Regulation of cytosolic prostaglandin E2 synthase by 90-kDa heat shock protein. Biochemical and biophysical research communications 303, 1018\u20131023 (2003).","journal-title":"Biochemical and biophysical research communications"},{"key":"BFsrep36985_CR110","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1743-8454-7-13","volume":"7","author":"AM Gonzalez","year":"2010","unstructured":"Gonzalez, A. M. et al. Co-localization and regulation of basic fibroblast growth factor and arginine vasopressin in neuroendocrine cells of the rat and human brain. Cerebrospinal Fluid Res 7, 13 (2010).","journal-title":"Cerebrospinal Fluid Res"},{"key":"BFsrep36985_CR111","unstructured":"Wu, B. K. Effect of foot reflexology on dysmenorrhoea in adolescents: A randomised controlled trial in Taiwan, Griffith University (2009)."},{"key":"BFsrep36985_CR112","first-page":"285","volume":"71","author":"L French","year":"2005","unstructured":"French, L. Dysmenorrhea. American family physician 71, 285 (2005).","journal-title":"American family physician"},{"key":"BFsrep36985_CR113","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3109\/00016347909157786","volume":"58","author":"M \u00c5kerlund","year":"1979","unstructured":"\u00c5kerlund, M. Pathophysiology of dysmenorrhea. Acta Obstetricia et Gynecologica Scandinavica 58, 27\u201332 (1979).","journal-title":"Acta Obstetricia et Gynecologica Scandinavica"},{"key":"BFsrep36985_CR114","first-page":"642","volume":"8","author":"Q Liu","year":"2002","unstructured":"Liu, Q. Nutgrass galingale rhizome\u2019s clinic application. Human Guiding Journal of TCMP 8, 642\u2013653 (2002).","journal-title":"Human Guiding Journal of TCMP"},{"key":"BFsrep36985_CR115","doi-asserted-by":"crossref","unstructured":"Kishi, T., Hirooka, Y. & Sunagawa, K. Impaired neurogenesis and activated caspase 3-dependent apoptosis pathway in the rostral ventrolateral medulla cause hypertension in stroke-prone spontaneously hypertensive rats. The FASEB Journal 22, 1234.1235 (2008).","DOI":"10.1096\/fasebj.22.1_supplement.1234.5"},{"key":"BFsrep36985_CR116","first-page":"383","volume":"13","author":"GH Corripio","year":"2010","unstructured":"Corripio, G. H., Vi\u00f1as, J. L. & Mart\u00ednez, A. S. Use of carbonic anhydrase ii for producing a drug: United States patent US 13, 383, 287 (12 July 2010).","journal-title":"United States patent US"},{"key":"BFsrep36985_CR117","doi-asserted-by":"crossref","unstructured":"Liano, F. & Pascual, J. Epidemiology of acute renal failure: a prospective, multicenter, community-based study. Kidney international 50 (1996).","DOI":"10.1038\/ki.1996.380"},{"key":"BFsrep36985_CR118","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1177\/000456328602300412","volume":"23","author":"M Houser","year":"1986","unstructured":"Houser, M. The effect of hydropenia and oral water loading on renal lysozyme handling and N-acetyl-beta-D-glucosaminidase excretion in man. Annals of clinical biochemistry 23, 453\u2013457 (1986).","journal-title":"Annals of clinical biochemistry"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep36985.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36985","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep36985.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T00:31:32Z","timestamp":1672878692000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep36985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,11,14]]},"references-count":118,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,12,23]]}},"alternative-id":["BFsrep36985"],"URL":"https:\/\/doi.org\/10.1038\/srep36985","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,14]]},"assertion":[{"value":"15 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 October 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"36985"}}