{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:57:15Z","timestamp":1791946635220,"version":"4.3.4"},"reference-count":107,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,1,1]],"date-time":"2020-01-01T00:00:00Z","timestamp":1577836800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100005272","name":"National Center for International Research","doi-asserted-by":"publisher","award":["2015B01022"],"award-info":[{"award-number":["2015B01022"]}],"id":[{"id":"10.13039\/501100005272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009600","name":"Traditional Chinese Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009600","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002338","name":"Health-cultivation Laboratory of the Ministry of Education","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002338","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of Ethnopharmacology"],"published-print":{"date-parts":[[2020,1]]},"DOI":"10.1016\/j.jep.2019.112128","type":"journal-article","created":{"date-parts":[[2019,8,3]],"date-time":"2019-08-03T17:54:14Z","timestamp":1564854854000},"page":"112128","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":79,"special_numbering":"C","title":["Prediction of the mechanisms of action of Shenkang in chronic kidney disease: A network pharmacology study and experimental validation"],"prefix":"10.1016","volume":"246","author":[{"given":"Tianyu","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zilin","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tonghua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jep.2019.112128_bib1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0076778","article-title":"The uremic toxin indoxyl sulphate enhances macrophage response to LPS","volume":"8","author":"Adesso","year":"2013","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2019.112128_bib2","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1038\/s41467-017-01201-3","article-title":"TRPV4 activation triggers protective responses to bacterial lipopolysaccharides in airway epithelial cells","volume":"8","author":"Alpizar","year":"2017","journal-title":"Nat. Commun."},{"key":"10.1016\/j.jep.2019.112128_bib3","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0173554","article-title":"Prevalence of chronic kidney disease and risk factors for its progression: a cross-sectional comparison of Indians living in Indian versus U.S. cities","volume":"12","author":"Anand","year":"2017","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2019.112128_bib4","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1146\/annurev.iy.11.040193.004003","article-title":"Endothelial-leukocyte adhesion molecules","volume":"11","author":"Bevilacqua","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"10.1016\/j.jep.2019.112128_bib5","doi-asserted-by":"crossref","first-page":"3690","DOI":"10.1681\/ASN.2015091014","article-title":"Stat3 controls tubulointerstitial communication during CKD","volume":"27","author":"Bienaime","year":"2016","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib6","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jep.2019.112128_bib7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ceca.2018.04.004","article-title":"Differential effects of lipopolysaccharide on mouse sensory TRP channels","volume":"73","author":"Boonen","year":"2018","journal-title":"Cell Calcium"},{"key":"10.1016\/j.jep.2019.112128_bib8","first-page":"178","article-title":"Many faces of Ras activation","volume":"1786","author":"Buday","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.jep.2019.112128_bib9","first-page":"465","article-title":"Clinical observation of shenkang injection in the treatment of senile cardiorenal syndrome","volume":"22","author":"Chen","year":"2013","journal-title":"Chin. Med. Emerg."},{"key":"10.1016\/j.jep.2019.112128_bib10","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1016\/j.jnutbio.2014.05.013","article-title":"Quercetin attenuates renal ischemia\/reperfusion injury via an activation of AMP-activated protein kinase-regulated autophagy pathway","volume":"25","author":"Chen","year":"2014","journal-title":"J. Nutr. Biochem."},{"key":"10.1016\/j.jep.2019.112128_bib11","doi-asserted-by":"crossref","first-page":"2786","DOI":"10.1681\/ASN.2016101101","article-title":"Plasma biomarkers and kidney function decline in early and established diabetic kidney disease","volume":"28","author":"Coca","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib12","doi-asserted-by":"crossref","first-page":"1258","DOI":"10.1038\/ki.2011.368","article-title":"The contribution of chronic kidney disease to the global burden of major noncommunicable diseases","volume":"80","author":"Couser","year":"2011","journal-title":"Kidney Int."},{"key":"10.1016\/j.jep.2019.112128_bib13","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1093\/eurjhf\/hfq112","article-title":"The vitamin D system: a crosstalk between the heart and kidney","volume":"12","author":"Cozzolino","year":"2010","journal-title":"Eur. J. Heart Fail."},{"key":"10.1016\/j.jep.2019.112128_bib14","first-page":"29","article-title":"Protective effects of Shenkang Injection against gentamin-induced kidney injury in rat","volume":"11","author":"Deng","year":"2013","journal-title":"Chin. J. Geriatr. Care"},{"key":"10.1016\/j.jep.2019.112128_bib15","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.biocel.2015.10.014","article-title":"TLR2-MyD88-NF-kappaB pathway is involved in tubulointerstitial inflammation caused by proteinuria","volume":"69","author":"Ding","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"10.1016\/j.jep.2019.112128_bib17","series-title":"Experimental Research on the Regulative Effects of Shenkang Injection on Abnormal Glomerular Mesangial Cells Cycle in High Glucose","author":"Du","year":"2003"},{"key":"10.1016\/j.jep.2019.112128_bib18","doi-asserted-by":"crossref","first-page":"272","DOI":"10.2174\/15701611113119990026","article-title":"Update on the biologic role of the vitamin D endocrine system","volume":"12","author":"Dusso","year":"2014","journal-title":"Curr. Vasc. Pharmacol."},{"key":"10.1016\/j.jep.2019.112128_bib19","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cytogfr.2017.03.003","article-title":"IL-6 signaling in diabetic nephropathy: from pathophysiology to therapeutic perspectives","volume":"37","author":"Feigerlova","year":"2017","journal-title":"Cytokine Growth Factor Rev."},{"key":"10.1016\/j.jep.2019.112128_bib21","first-page":"11","article-title":"Effect of shenkang injection on senescence of renal tubular cell induced by high glucose","volume":"17","author":"Fu","year":"2016","journal-title":"Chin. J. Integrated Tradit. West. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib22","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1681\/ASN.2011060628","article-title":"Circulating TNF receptors 1 and 2 predict stage 3 CKD in type 1 diabetes","volume":"23","author":"Gohda","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib25","first-page":"50","article-title":"Contrast study on effect of shenkang injection and benazepril on human glomerular mesangial extracellular matrix","volume":"20","author":"Guo","year":"2000","journal-title":"Chin. J. Integr. Tradit. West. Med."},{"key":"10.1016\/j.jep.2019.112128_bib26","doi-asserted-by":"crossref","first-page":"484","DOI":"10.3390\/ijms15010484","article-title":"The inhibitory effect of quercetin on asymmetric dimethylarginine-induced apoptosis is mediated by the endoplasmic reticulum stress pathway in glomerular endothelial cells","volume":"15","author":"Guo","year":"2014","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.jep.2019.112128_bib27","series-title":"Experimental Research on the Eeffets of Shenkang Lnjection on Transdiffrentiation of Renal Tubular Epihtelial Cells Indueed by BSA in Vitro","author":"He","year":"2005"},{"key":"10.1016\/j.jep.2019.112128_bib28","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/j.ejphar.2016.07.003","article-title":"Protective role of apigenin in cisplatin-induced renal injury","volume":"789","author":"He","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"10.1016\/j.jep.2019.112128_bib29","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1038\/ki.2011.223","article-title":"Cardiovascular disease in chronic kidney disease. A clinical update from Kidney Disease: improving Global Outcomes (KDIGO)","volume":"80","author":"Herzog","year":"2011","journal-title":"Kidney Int."},{"key":"10.1016\/j.jep.2019.112128_bib30","doi-asserted-by":"crossref","first-page":"620","DOI":"10.3389\/fphar.2018.00620","article-title":"Exploring the therapeutic mechanism of Desmodium styracifolium on oxalate crystal-induced kidney injuries using comprehensive approaches based on proteomics and network pharmacology","volume":"9","author":"Hou","year":"2018","journal-title":"Front. Pharmacol."},{"key":"10.1016\/j.jep.2019.112128_bib31","doi-asserted-by":"crossref","first-page":"7258","DOI":"10.1021\/jf304595p","article-title":"Rutin (quercetin rutinoside) induced protein-energy malnutrition in chronic kidney disease, but quercetin acted beneficially","volume":"61","author":"Hsieh","year":"2013","journal-title":"J. Agric. Food Chem."},{"key":"10.1016\/j.jep.2019.112128_bib32","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1016\/j.bbadis.2007.02.001","article-title":"TRP channels in kidney disease","volume":"1772","author":"Hsu","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"10.1016\/j.jep.2019.112128_bib35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/s13020-018-0170-4","article-title":"Approaches in studying the pharmacology of Chinese Medicine formulas: bottom-up, top-down-and meeting in the middle","volume":"13","author":"Huang","year":"2018","journal-title":"Chin. Med."},{"key":"10.1016\/j.jep.2019.112128_bib36","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/ajh.2009.68","article-title":"Maternal adaptation in pregnant hypertensive rats: improvement of vascular and inflammatory variables and oxidative damage in the kidney","volume":"22","author":"Iacono","year":"2009","journal-title":"Am. J. Hypertens."},{"key":"10.1016\/j.jep.2019.112128_bib37","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0089355","article-title":"Iron chelation by deferoxamine prevents renal interstitial fibrosis in mice with unilateral ureteral obstruction","volume":"9","author":"Ikeda","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2019.112128_bib38","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1254\/jphs.08R08FM","article-title":"Drug discovery for overcoming chronic kidney disease (CKD): development of drugs on endothelial cell protection for overcoming CKD","volume":"109","author":"Ishizawa","year":"2009","journal-title":"J. Pharmacol. Sci."},{"key":"10.1016\/j.jep.2019.112128_bib39","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1111\/hdi.12587","article-title":"The nature, consequences, and management of neurological disorders in chronic kidney disease","volume":"22","author":"Jabbari","year":"2018","journal-title":"Hemodial. Int."},{"key":"10.1016\/j.jep.2019.112128_bib40","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1111\/j.1365-201X.2004.01330.x","article-title":"The renin-angiotensin system in kidney development: role of COX-2 and adrenal steroids","volume":"181","author":"Jensen","year":"2004","journal-title":"Acta Physiol. Scand."},{"issue":"Suppl. 2","key":"10.1016\/j.jep.2019.112128_bib41","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/j.1440-1797.2010.01305.x","article-title":"Herbal medicines and chronic kidney disease","volume":"15","author":"Jha","year":"2010","journal-title":"Nephrology"},{"key":"10.1016\/j.jep.2019.112128_bib42","first-page":"2535","article-title":"Effect of shenkang injection on renal tubular epithelial cells damaged by aristolochic acid","volume":"31","author":"Ji","year":"2013","journal-title":"Chin. Arch. Trad. Chin. Med."},{"key":"10.1016\/j.jep.2019.112128_bib43","first-page":"941","article-title":"The phase IV clinical observation study of shenkang injection on chronic renal failure","volume":"40","author":"Jiang","year":"2011","journal-title":"J. China Med. Univ."},{"key":"10.1016\/j.jep.2019.112128_bib44","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1002\/mc.22548","article-title":"CACNA2D3 is downregulated in gliomas and functions as a tumor suppressor","volume":"56","author":"Jin","year":"2017","journal-title":"Mol. Carcinog."},{"key":"10.1016\/j.jep.2019.112128_bib45","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/jcp.22704","article-title":"Primary cilia regulates the directional migration and barrier integrity of endothelial cells through the modulation of hsp27 dependent actin cytoskeletal organization","volume":"227","author":"Jones","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"10.1016\/j.jep.2019.112128_bib46","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s40139-013-0026-7","article-title":"Matrix producing cells in chronic kidney disease: origin, regulation, and activation","volume":"1","author":"Kramann","year":"2013","journal-title":"Curr. Pathobiol. Rep."},{"key":"10.1016\/j.jep.2019.112128_bib47","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1093\/ndt\/gfs485","article-title":"Sailing between Scylla and Charybdis: oral long-term anticoagulation in dialysis patients","volume":"28","author":"Kruger","year":"2013","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.jep.2019.112128_bib48","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1159\/000330349","article-title":"Purinergic P2X7 receptors participate in disturbed intracellular calcium homeostasis in peripheral blood mononuclear cells of patients with chronic kidney disease","volume":"35","author":"Lajdova","year":"2012","journal-title":"Kidney Blood Press. Res."},{"key":"10.1016\/j.jep.2019.112128_bib49","first-page":"20","article-title":"Effect of shenkang injection on transforming growth factor-\u03b2 1 and bone morphogenetic protein-7 in rats with unilateral ureteral obstruction","volume":"41","author":"Lan","year":"2008","journal-title":"China Pharm."},{"key":"10.1016\/j.jep.2019.112128_bib50","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.bbrc.2013.03.108","article-title":"Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells","volume":"434","author":"Lee","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.jep.2019.112128_bib51","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.1016\/j.bmcl.2015.10.035","article-title":"Protective effect and mechanism of action of lupane triterpenes from Cornus walteri in cisplatin-induced nephrotoxicity","volume":"25","author":"Lee","year":"2015","journal-title":"Bioorg. Med. Chem. Lett"},{"key":"10.1016\/j.jep.2019.112128_bib52","first-page":"42","article-title":"Effect of shenkang injection on level of endogenous NO of glomerular mesangial cell","volume":"19","author":"Li","year":"2000","journal-title":"J. Anhui TCM Coll."},{"key":"10.1016\/j.jep.2019.112128_bib55","doi-asserted-by":"crossref","first-page":"15290","DOI":"10.1038\/srep15290","article-title":"Systems pharmacology-based dissection of mechanisms of Chinese medicinal formula Bufei Yishen as an effective treatment for chronic obstructive pulmonary disease","volume":"5","author":"Li","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jep.2019.112128_bib57","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1681\/ASN.2010111210","article-title":"Toll-like receptor 4 promotes tubular inflammation in diabetic nephropathy","volume":"23","author":"Lin","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib59","series-title":"The Protection Effects and Mechanism Research of Shen-Kang and Medicinal Substances on Chronic Kidney Disease in Vivo and in Vitro","author":"Liu","year":"2015"},{"key":"10.1016\/j.jep.2019.112128_bib60","series-title":"The Early Changes of Renal Tubulointerstitial and Their Treatments in Rats with Diabetes. Chinese PLA General Hospital & Medical School PLA","author":"Liu","year":"2015"},{"key":"10.1016\/j.jep.2019.112128_bib62","doi-asserted-by":"crossref","first-page":"938764","DOI":"10.1155\/2013\/938764","article-title":"A systems-pharmacology analysis of herbal medicines used in health improvement treatment: predicting potential new drugs and targets","volume":"2013","author":"Liu","year":"2013","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"10.1016\/j.jep.2019.112128_bib63","doi-asserted-by":"crossref","first-page":"975","DOI":"10.3892\/ijmm.2015.2328","article-title":"Shen-Kang protects 5\/6 nephrectomized rats against renal injury by reducing oxidative stress through the MAPK signaling pathways","volume":"36","author":"Liu","year":"2015","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.jep.2019.112128_bib65","doi-asserted-by":"crossref","first-page":"19809","DOI":"10.1038\/srep19809","article-title":"Systems-pharmacology dissection of traditional Chinese medicine compound saffron formula reveals multi-scale treatment strategy for cardiovascular diseases","volume":"6","author":"Liu","year":"2016","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jep.2019.112128_bib66","first-page":"9025036","article-title":"Systems pharmacology uncovers the multiple mechanisms of xijiao dihuang decoction for the treatment of viral hemorrhagic fever. Evid. Based complement","volume":"2016","author":"Liu","year":"2016","journal-title":"Altern. Med."},{"key":"10.1016\/j.jep.2019.112128_bib67","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/jcmm.13060","article-title":"Signalling pathways involved in hypoxia-induced renal fibrosis","volume":"21","author":"Liu","year":"2017","journal-title":"J. Cell Mol. Med."},{"key":"10.1016\/j.jep.2019.112128_bib68","doi-asserted-by":"crossref","first-page":"1799","DOI":"10.1016\/j.biopha.2017.09.091","article-title":"Effects of apigenin pretreatment against renal ischemia\/reperfusion injury via activation of the JAK2\/STAT3 pathway","volume":"95","author":"Liu","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.jep.2019.112128_bib69","first-page":"5345","article-title":"Effects of apigenin on the expression levels of B-cell lymphoma-2, Fas and Fas ligand in renal ischemia-reperfusion injury in rats","volume":"14","author":"Liu","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.jep.2019.112128_bib70","first-page":"206","volume":"vol. 43","author":"Liu","year":"2018"},{"key":"10.1016\/j.jep.2019.112128_bib71","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1053\/j.ackd.2012.04.005","article-title":"Nephrotoxicity of alternative medicine practice","volume":"19","author":"Luyckx","year":"2012","journal-title":"Adv. Chron. Kidney Dis."},{"key":"10.1016\/j.jep.2019.112128_bib72","doi-asserted-by":"crossref","first-page":"386","DOI":"10.2174\/1568026611313030013","article-title":"TRP channels as therapeutic targets in kidney disease and hypertension","volume":"13","author":"Mene","year":"2013","journal-title":"Curr. Top. Med. Chem."},{"key":"10.1016\/j.jep.2019.112128_bib73","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.arcmed.2013.10.009","article-title":"Chronic kidney disease and hypothalamic\u2013pituitary Axis dysfunction: the chicken or the egg?","volume":"44","author":"Meuwese","year":"2013","journal-title":"Arch. Med. Res."},{"key":"10.1016\/j.jep.2019.112128_bib74","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1007\/s11096-016-0298-1","article-title":"Prescribing patterns of non-steroidal anti-inflammatory drugs in chronic kidney disease patients in the South African private sector","volume":"38","author":"Meuwesen","year":"2016","journal-title":"Int. J. Clin. Pharm."},{"key":"10.1016\/j.jep.2019.112128_bib75","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1681\/ASN.2016040486","article-title":"Hyperoxaluria requires TNF receptors to initiate crystal adhesion and kidney stone disease","volume":"28","author":"Mulay","year":"2017","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib76","doi-asserted-by":"crossref","first-page":"1830","DOI":"10.2337\/dc15-1182","article-title":"Fatty liver and chronic kidney disease: novel mechanistic insights and therapeutic opportunities","volume":"39","author":"Musso","year":"2016","journal-title":"Diabetes Care"},{"key":"10.1016\/j.jep.2019.112128_bib77","doi-asserted-by":"crossref","first-page":"896","DOI":"10.3389\/fphys.2017.00896","article-title":"Lung oxidative stress, DNA damage, apoptosis, and fibrosis in adenine-induced chronic kidney disease in mice","volume":"8","author":"Nemmar","year":"2017","journal-title":"Front. Physiol."},{"key":"10.1016\/j.jep.2019.112128_bib78","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1159\/000343742","article-title":"Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease","volume":"36","author":"Okada","year":"2012","journal-title":"Am. J. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib79","first-page":"43","article-title":"Effects of shenkang injection on proliferation of glomerular mesangial cells","volume":"16","author":"Peng","year":"2000","journal-title":"Res. Trad. Chin. Med."},{"key":"10.1016\/j.jep.2019.112128_bib80","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1002\/mnfr.201200178","article-title":"Selected nutraceutic screening by therapeutic effects on doxorubicin-induced chronic kidney disease","volume":"56","author":"Peng","year":"2012","journal-title":"Mol. Nutr. Food Res."},{"key":"10.1016\/j.jep.2019.112128_bib81","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0142510","article-title":"Deregulated renal calcium and phosphate transport during experimental kidney failure","volume":"10","author":"Pulskens","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.jep.2019.112128_bib83","doi-asserted-by":"crossref","first-page":"3496","DOI":"10.2741\/3467","article-title":"NF-kappaB signalling in chronic kidney disease","volume":"14","author":"Rangan","year":"2009","journal-title":"Front. Biosci."},{"key":"10.1016\/j.jep.2019.112128_bib84","doi-asserted-by":"crossref","first-page":"6019","DOI":"10.1073\/pnas.0701319104","article-title":"Toll-like receptor-MyD88 and Fc receptor pathways of mast cells mediate the thyroid dysfunctions observed during nonthyroidal illness","volume":"104","author":"Rocchi","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"10.1016\/j.jep.2019.112128_bib85","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/1758-2946-6-13","article-title":"TCMSP: a database of systems pharmacology for drug discovery from herbal medicines","volume":"6","author":"Ru","year":"2014","journal-title":"J. Cheminf."},{"key":"10.1016\/j.jep.2019.112128_bib86","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13479","article-title":"Pro-resolving lipid mediators are leads for resolution physiology","volume":"510","author":"Serhan","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.jep.2019.112128_bib87","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/kisup.2014.21","article-title":"Obesity, oxidative stress, and fibrosis in chronic kidney disease","volume":"4","author":"Sharma","year":"2014","journal-title":"Kidney Int. Suppl."},{"key":"10.1016\/j.jep.2019.112128_bib88","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.prostaglandins.2017.01.003","article-title":"Hyperfiltration-associated biomechanical forces in glomerular injury and response: potential role for eicosanoids","volume":"132","author":"Sharma","year":"2017","journal-title":"Prostaglandins Other Lipid Mediat."},{"key":"10.1016\/j.jep.2019.112128_bib89","first-page":"10","article-title":"Shenkang injection solution antagonizes the fibrogenic effects of aristolochic acid on human proximal tubular epithelial cells in vitro","volume":"9","author":"Shen","year":"2008","journal-title":"Chin. J. Integrated Tradit. West. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib90","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/bioinformatics\/btq675","article-title":"Cytoscape 2.8: new features for data integration and network visualization","volume":"27","author":"Smoot","year":"2011","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jep.2019.112128_bib91","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1126\/science.319.5864.709","article-title":"Lifting the veil on traditional Chinese medicine","volume":"319","author":"Stone","year":"2008","journal-title":"Science"},{"key":"10.1016\/j.jep.2019.112128_bib92","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1053\/j.ajkd.2017.05.021","article-title":"Lung function and incident kidney disease: the atherosclerosis risk in communities (ARIC) study","volume":"70","author":"Sumida","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"10.1016\/j.jep.2019.112128_bib93","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2017-019097","article-title":"Fatty liver index, albuminuria and the association with chronic kidney disease: a population-based study in China","volume":"8","author":"Sun","year":"2018","journal-title":"Bmj Open"},{"key":"10.1016\/j.jep.2019.112128_bib94","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1159\/000325647","article-title":"Diabetic tubulopathy: an emerging entity","volume":"170","author":"Tang","year":"2011","journal-title":"Contrib. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib95","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1038\/ki.2013.97","article-title":"Signal regulatory protein-alpha interacts with the insulin receptor contributing to muscle wasting in chronic kidney disease","volume":"84","author":"Thomas","year":"2013","journal-title":"Kidney Int."},{"key":"10.1016\/j.jep.2019.112128_bib96","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1007\/s00281-015-0527-z","article-title":"Role of renal TRP channels in physiology and pathology","volume":"38","author":"Tomilin","year":"2016","journal-title":"Semin. Immunopathol."},{"key":"10.1016\/j.jep.2019.112128_bib97","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.2215\/CJN.09640911","article-title":"Urinary biomarkers in obstructive nephropathy","volume":"7","author":"Trnka","year":"2012","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib98","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1016\/j.jep.2011.12.009","article-title":"Optimized project of traditional Chinese medicine in treating chronic kidney disease stage 3: a multicenter double-blinded randomized controlled trial","volume":"139","author":"Wang","year":"2012","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.jep.2019.112128_bib99","first-page":"980190","article-title":"Systems pharmacology dissecting holistic medicine for treatment of complex diseases: an example using cardiocerebrovascular diseases treated by TCM. Evid. Based complement","volume":"2015","author":"Wang","year":"2015","journal-title":"Altern. Med."},{"key":"10.1016\/j.jep.2019.112128_bib100","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.bcp.2017.08.016","article-title":"Parathyroid hormone contributes to the down-regulation of cytochrome P450 3A through the cAMP\/PI3K\/PKC\/PKA\/NF-kappaB signaling pathway in secondary hyperparathyroidism","volume":"145","author":"Watanabe","year":"2017","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.jep.2019.112128_bib101","article-title":"Complications of CKD: current state, knowledge gaps, and strategy for action","volume":"7","author":"Wheeler","year":"2017","journal-title":"Kidney Int. Suppl."},{"key":"10.1016\/j.jep.2019.112128_bib102","author":"World Health Organization"},{"key":"10.1016\/j.jep.2019.112128_bib103","series-title":"Studies on Protective Effects and Mechanisms of ShenKang Injection and Effective Substances on Chronic Renal Disease","author":"Wu","year":"2015"},{"key":"10.1016\/j.jep.2019.112128_bib104","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1111\/jphp.12412","article-title":"ShenKang injection suppresses kidney fibrosis and oxidative stress via transforming growth factor-beta\/Smad3 signalling pathway in vivo and in vitro","volume":"67","author":"Wu","year":"2015","journal-title":"J. Pharm. Pharmacol."},{"key":"10.1016\/j.jep.2019.112128_bib105","first-page":"1434","article-title":"The effects of shenkang injection on STZ induced diabetic nephropathy rat models","volume":"15","author":"Xu","year":"2015","journal-title":"Prog. Mod. Biomed."},{"key":"10.1016\/j.jep.2019.112128_bib106","doi-asserted-by":"crossref","first-page":"i246","DOI":"10.1093\/bioinformatics\/btq176","article-title":"Drug-target interaction prediction from chemical, genomic and pharmacological data in an integrated framework","volume":"26","author":"Yamanishi","year":"2010","journal-title":"Bioinformatics"},{"key":"10.1016\/j.jep.2019.112128_bib107","series-title":"Effects of Shenkang Injection on Cultured Rat Kidney Interstitial Fibroblast","author":"Yang","year":"2002"},{"key":"10.1016\/j.jep.2019.112128_bib108","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1186\/1472-6882-14-430","article-title":"A novel systems pharmacology model for herbal medicine injection: a case using Reduning injection","volume":"14","author":"Yang","year":"2014","journal-title":"BMC Complement Altern. Med."},{"key":"10.1016\/j.jep.2019.112128_bib109","first-page":"3805","article-title":"Effects and mechanisms of Shenkang injection promoting extracellular matrix degradation via regulating ERK1\/2\/MMPs signaling pathway in renal failure rats","volume":"41","author":"Yang","year":"2016","journal-title":"China J. Chin. Mater. Med."},{"key":"10.1016\/j.jep.2019.112128_bib110","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1093\/ndt\/gfv353","article-title":"Gut Lactobacillus protects against the progression of renal damage by modulating the gut environment in rats","volume":"31","author":"Yoshifuji","year":"2016","journal-title":"Nephrol. Dial. Transplant."},{"key":"10.1016\/j.jep.2019.112128_bib111","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1007\/s10157-018-1577-z","article-title":"Oral adsorbent AST-120 ameliorates gut environment and protects against the progression of renal impairment in CKD rats","volume":"22","author":"Yoshifuji","year":"2018","journal-title":"Clin. Exp. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib113","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.neuroscience.2013.12.060","article-title":"Src regulates angiogenic factors and vascular permeability after focal cerebral ischemia-reperfusion","volume":"262","author":"Zan","year":"2014","journal-title":"Neuroscience"},{"key":"10.1016\/j.jep.2019.112128_bib114","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1681\/ASN.2010060594","article-title":"Cyclooxygenase 2 promotes parathyroid hyperplasia in ESRD","volume":"22","author":"Zhang","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"10.1016\/j.jep.2019.112128_bib115","first-page":"2248","article-title":"Effect of shenkang injection on kidney function in hypertensive renal damage rats","volume":"37","author":"Zhang","year":"2014","journal-title":"Zhong Yao Cai"},{"key":"10.1016\/j.jep.2019.112128_bib116","doi-asserted-by":"crossref","first-page":"2034","DOI":"10.3892\/etm.2015.2383","article-title":"Effect of Shenkang granules on the progression of chronic renal failure in 5\/6 nephrectomized rats","volume":"9","author":"Zhang","year":"2015","journal-title":"Exp. Ther. Med."},{"key":"10.1016\/j.jep.2019.112128_bib118","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1038\/aps.2018.12","article-title":"Xyloketal B exerts antihypertensive effect in renovascular hypertensive rats via the NO-sGC-cGMP pathway and calcium signaling","volume":"39","author":"Zhao","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.jep.2019.112128_bib119","doi-asserted-by":"crossref","first-page":"11970","DOI":"10.1038\/srep11970","article-title":"Large-scale direct targeting for drug repositioning and discovery","volume":"5","author":"Zheng","year":"2015","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jep.2019.112128_bib120","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ejps.2016.05.018","article-title":"A novel systems pharmacology platform to dissect action mechanisms of traditional Chinese medicines for bovine viral diarrhea disease","volume":"94","author":"Zheng","year":"2016","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.jep.2019.112128_bib121","first-page":"121","article-title":"Effects of Shenkang Injection on blood pressure and related factors of hypertensive renal disease rats","volume":"36","author":"Zhou","year":"2015","journal-title":"J. Xi'an Jiaot. Univ."},{"key":"10.1016\/j.jep.2019.112128_bib122","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.drudis.2006.11.008","article-title":"Multi-target therapeutics: when the whole is greater than the sum of the parts","volume":"12","author":"Zimmermann","year":"2007","journal-title":"Drug Discov. Today"}],"updated-by":[{"DOI":"10.1016\/j.jep.2025.119922","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000}}],"container-title":["Journal of Ethnopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874118344568?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0378874118344568?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T16:28:53Z","timestamp":1759940933000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0378874118344568"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1]]},"references-count":107,"alternative-id":["S0378874118344568"],"URL":"https:\/\/doi.org\/10.1016\/j.jep.2019.112128","relation":{"erratum":[{"id-type":"doi","id":"10.1016\/j.jep.2025.119922","asserted-by":"object"}]},"ISSN":["0378-8741"],"issn-type":[{"value":"0378-8741","type":"print"}],"subject":[],"published":{"date-parts":[[2020,1]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Prediction of the mechanisms of action of Shenkang in chronic kidney disease: A network pharmacology study and experimental validation","name":"articletitle","label":"Article Title"},{"value":"Journal of Ethnopharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jep.2019.112128","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"112128"}}