{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:29:24Z","timestamp":1787002164151,"version":"build-2736575974"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T00:00:00Z","timestamp":1496016000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Acta Pharmacol Sin"],"published-print":{"date-parts":[[2017,8]]},"DOI":"10.1038\/aps.2017.19","type":"journal-article","created":{"date-parts":[[2017,5,29]],"date-time":"2017-05-29T05:01:37Z","timestamp":1496034097000},"page":"1150-1160","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Plumbagin suppresses chronic periodontitis in rats via down-regulation of TNF-\u03b1, IL-1\u03b2 and IL-6 expression"],"prefix":"10.1038","volume":"38","author":[{"given":"Xin-yi","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuan-yuan","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-yu","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Er-yi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,5,29]]},"reference":[{"key":"BFaps201719_CR1","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1902\/annals.1999.4.1.32","volume":"4","author":"TF Flemmig","year":"1999","unstructured":"Flemmig TF . Periodontitis. Ann Periodontol 1999; 4: 32\u20138.","journal-title":"Ann Periodontol"},{"key":"BFaps201719_CR2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/j.1600-0757.2009.00307.x","volume":"52","author":"A Amano","year":"2010","unstructured":"Amano A . Bacterial adhesins to host components in periodontitis. Periodontol 2000 2010; 52: 12\u201337.","journal-title":"Periodontol 2000"},{"key":"BFaps201719_CR3","first-page":"95","volume":"18","author":"R Liu","year":"2012","unstructured":"Liu R, Li N, Liu N, Zhou X, Dong ZM, Wen XJ, et al. Effects of systemic ornidazole, systemic and local compound ornidazole and pefloxacin mesylate on experimental periodontitis in rats. Med Sci Monit 2012; 18: 95\u2013102.","journal-title":"Med Sci Monit"},{"key":"BFaps201719_CR4","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1111\/prd.12075","volume":"67","author":"M Feres","year":"2015","unstructured":"Feres M, Figueiredo LC, Soares GM, Faveri M . Systemic antibiotics in the treatment of periodontitis. Periodontol 2000 2015; 67: 131\u201386.","journal-title":"Periodontol 2000"},{"key":"BFaps201719_CR5","doi-asserted-by":"publisher","first-page":"2581876","DOI":"10.1155\/2016\/2581876","volume":"2016","author":"Y Sekita","year":"2016","unstructured":"Sekita Y, Murakami K, Yumoto H, Amoh T, Fujiwara N . Ogata S, et al. Preventive effects of Houttuynia cordata extract for oral infectious diseases. Biomed Res Int 2016; 2016: 2581876.","journal-title":"Biomed Res Int"},{"key":"BFaps201719_CR6","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.intimp.2016.04.010","volume":"36","author":"Y Wang","year":"2016","unstructured":"Wang Y, Zhang H, Du G, Wang Y, Cao T, Luo Q, et al. Total glucosides of paeony (TGP) inhibits the production of inflammatory cytokines in oral lichen planus by suppressing the NF-kappaB signaling pathway. Int Immunopharmacol 2016; 36: 67\u201372.","journal-title":"Int Immunopharmacol"},{"key":"BFaps201719_CR7","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1021\/tx034132s","volume":"17","author":"JJ Inbaraj","year":"2004","unstructured":"Inbaraj JJ, Chignell CF . Cytotoxic action of juglone and plumbagin: a mechanistic study using HaCaT keratinocytes. Chem Res Toxicol 2004; 17: 55\u201362.","journal-title":"Chem Res Toxicol"},{"key":"BFaps201719_CR8","first-page":"14432","volume":"8","author":"CH Yan","year":"2015","unstructured":"Yan CH, Li F, Ma YC . Plumbagin shows anticancer activity in human osteosarcoma (MG-63) cells via the inhibition of S-Phase checkpoints and down-regulation of c-myc. Int J Clin Exp Med 2015; 8: 14432\u20139.","journal-title":"Int J Clin Exp Med"},{"key":"BFaps201719_CR9","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1002\/med.20235","volume":"32","author":"S Padhye","year":"2012","unstructured":"Padhye S, Dandawate P, Yusufi M, Ahmad A, Sarkar FH . Perspectives on medicinal properties of plumbagin and its analogs. Med Res Rev 2012; 32: 1131\u201358.","journal-title":"Med Res Rev"},{"key":"BFaps201719_CR10","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1124\/jpet.110.170852","volume":"335","author":"P Luo","year":"2010","unstructured":"Luo P, Wong YF, Ge L, Zhang ZF, Liu Y, Liu L, et al. Anti-inflammatory and analgesic effect of plumbagin through inhibition of nuclear factor-kappaB activation. J Pharmacol Exp Ther 2010; 335: 735\u201342.","journal-title":"J Pharmacol Exp Ther"},{"key":"BFaps201719_CR11","doi-asserted-by":"publisher","first-page":"1669","DOI":"10.3892\/ijmm.2016.2564","volume":"37","author":"H Chu","year":"2016","unstructured":"Chu H, Yu H, Ren D, Zhu K, Huang H . Plumbagin exerts protective effects in nucleus pulposus cells by attenuating hydrogen peroxide-induced oxidative stress, inflammation and apoptosis through NF-kappaB and Nrf-2. Int J Mol Med 2016; 37: 1669\u201376.","journal-title":"Int J Mol Med"},{"key":"BFaps201719_CR12","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1007\/s12192-015-0585-0","volume":"20","author":"S Zhang","year":"2015","unstructured":"Zhang S, Li D, Yang JY, Yan TB . Plumbagin protects against glucocorticoid-induced osteoporosis through Nrf-2 pathway. Cell Stress Chaperones 2015; 20: 621\u20139.","journal-title":"Cell Stress Chaperones"},{"key":"BFaps201719_CR13","doi-asserted-by":"publisher","first-page":"4585","DOI":"10.1111\/febs.12429","volume":"280","author":"A Bhattacharya","year":"2013","unstructured":"Bhattacharya A, Jindal B, Singh P, Datta A, Panda D . Plumbagin inhibits cytokinesis in Bacillus subtilis by inhibiting FtsZ assembly-a mechanistic study of its antibacterial activity. FEBS J 2013; 280: 4585\u201399.","journal-title":"FEBS J"},{"key":"BFaps201719_CR14","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.12659\/MSM.897618","volume":"22","author":"SX Wang","year":"2016","unstructured":"Wang SX, Wang J, Shao JB, Tang WN, Zhong JQ . Plumbagin mediates cardioprotection against myocardial ischemia\/reperfusion injury through Nrf-2 signaling. Med Sci Monit 2016; 22: 1250\u20137.","journal-title":"Med Sci Monit"},{"key":"BFaps201719_CR15","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/j.fct.2013.11.027","volume":"64","author":"T Wang","year":"2014","unstructured":"Wang T, Wu F, Jin Z, Zhai Z, Wang Y, Ti B, et al. Plumbagin inhibits LPS-induced inflammation through the inactivation of the nuclear factor-kappa B and mitogen activated protein kinase signaling pathways in RAW 264.7 cells. Food Chem Toxicol 2014; 64: 177\u201383.","journal-title":"Food Chem Toxicol"},{"key":"BFaps201719_CR16","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/aps.2013.152","volume":"35","author":"W Yan","year":"2014","unstructured":"Yan W, Wang TY, Fan QM, Du L, Xu JK, Zhai ZJ, et al. Plumbagin attenuates cancer cell growth and osteoclast formation in the bone microenvironment of mice. Acta Pharmacol Sin 2014; 35: 124\u201334.","journal-title":"Acta Pharmacol Sin"},{"key":"BFaps201719_CR17","doi-asserted-by":"publisher","first-page":"e2094","DOI":"10.1038\/cddis.2016.11","volume":"7","author":"H Qiao","year":"2016","unstructured":"Qiao H, Wang TY, Yu ZF, Han XG, Liu XQ, Wang YG, et al. Structural simulation of adenosine phosphate via plumbagin and zoledronic acid competitively targets JNK\/Erk to synergistically attenuate osteoclastogenesis in a breast cancer model. Cell Death Dis 2016; 7: e2094.","journal-title":"Cell Death Dis"},{"key":"BFaps201719_CR18","doi-asserted-by":"publisher","first-page":"4127","DOI":"10.1128\/IAI.02084-14","volume":"82","author":"J Lin","year":"2014","unstructured":"Lin J, Bi L, Yu X, Kawai T, Taubman MA, Shen B, et al. Porphyromonas gingivalis exacerbates ligature-induced, RANKL-dependent alveolar bone resorption via differential regulation of Toll-like receptor 2 (TLR2) and TLR4. Infect Immun 2014; 82: 4127\u201334.","journal-title":"Infect Immun"},{"key":"BFaps201719_CR19","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1046\/j.0303-6979.2003.00425.x","volume":"30","author":"R G\u00f3rska","year":"2003","unstructured":"G\u00f3rska R, Gregorek H, Kowalski J, Laskus-Perendyk A, Syczewska M, Madali\u00f1ski K . Relationship between clinical parameters and cytokine profiles in inflamed gingival tissue and serum samples from patients with chronic periodontitis. J Clin Periodontol 2003; 30: 1046\u201352.","journal-title":"J Clin Periodontol"},{"key":"BFaps201719_CR20","first-page":"60","volume":"29","author":"V Deo","year":"2010","unstructured":"Deo V, Bhongade ML . Pathogenesis of periodontitis: role of cytokines in host response. Dent Today 2010; 29: 60\u20132.","journal-title":"Dent Today"},{"key":"BFaps201719_CR21","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/prd.12070","volume":"67","author":"AR Sanz","year":"2015","unstructured":"Sanz AR, Carrion FS, Chaparro AP . Mesenchymal stem cells from the oral cavity and their potential value in tissue engineering. Periodontol 2000 2015; 67: 251\u201367.","journal-title":"Periodontol 2000"},{"key":"BFaps201719_CR22","doi-asserted-by":"publisher","first-page":"915","DOI":"10.3892\/ijmm.2015.2314","volume":"36","author":"W Zheng","year":"2015","unstructured":"Zheng W, Wang S, Wang J, Jin F . Periodontitis promotes the proliferation and suppresses the differentiation potential of human periodontal ligament stem cells. Int J Mol Med 2015; 36: 915\u201322.","journal-title":"Int J Mol Med"},{"key":"BFaps201719_CR23","doi-asserted-by":"publisher","first-page":"721","DOI":"10.1111\/j.1600-051X.2011.01716.x","volume":"38","author":"JC Park","year":"2011","unstructured":"Park JC, Kim JM, Jung IH, Kim JC, Choi SH, Cho KS, et al. Isolation and characterization of human periodontal ligament (PDL) stem cells (PDLSCs) from the inflamed PDL tissue: in vitro and in vivo evaluations. J Clin Periodontol 2011; 38: 721\u201331.","journal-title":"J Clin Periodontol"},{"key":"BFaps201719_CR24","doi-asserted-by":"publisher","first-page":"e2296","DOI":"10.1038\/cddis.2016.204","volume":"7","author":"CY Mao","year":"2016","unstructured":"Mao CY, Wang YG . Zhang, Zheng XY, Tang TT, Lu EY . Double-edged-sword effect of IL-1beta on the osteogenesis of periodontal ligament stem cells via crosstalk between the NF-kappaB, MAPK and BMP\/Smad signaling pathways. Cell Death Dis 2016; 7: e2296.","journal-title":"Cell Death Dis"},{"key":"BFaps201719_CR25","doi-asserted-by":"publisher","first-page":"2563","DOI":"10.1016\/j.bbamcr.2014.05.014","volume":"1843","author":"MD Turner","year":"2014","unstructured":"Turner MD, Nedjai B, Hurst T, Pennington DJ . Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 2014; 1843: 2563\u201382.","journal-title":"Biochim Biophys Acta"},{"key":"BFaps201719_CR26","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s00204-015-1472-2","volume":"89","author":"EK Kim","year":"2015","unstructured":"Kim EK, Choi EJ . Compromised MAPK signaling in human diseases: an update. Arch Toxicol 2015; 89: 867\u201382.","journal-title":"Arch Toxicol"},{"key":"BFaps201719_CR27","doi-asserted-by":"publisher","first-page":"55","DOI":"10.2174\/138955711793564079","volume":"11","author":"YA Ivanenkov","year":"2011","unstructured":"Ivanenkov YA, Balakin KV, Lavrovsky Y . Small molecule inhibitors of NF-kB and JAK\/STAT signal transduction pathways as promising anti-inflammatory therapeutics. Mini Rev Med Chem 2011; 11: 55\u201378.","journal-title":"Mini Rev Med Chem"},{"key":"BFaps201719_CR28","doi-asserted-by":"publisher","first-page":"3494","DOI":"10.3892\/mmr.2015.3875","volume":"12","author":"XC Xu","year":"2015","unstructured":"Xu XC, Chen H, Zhang X, Zhai ZJ, Liu XQ, Zheng XY, et al. Effects of oestrogen deficiency on the alveolar bone of rats with experimental periodontitis. Mol Med Rep 2015; 12: 3494\u2013502.","journal-title":"Mol Med Rep"},{"key":"BFaps201719_CR29","doi-asserted-by":"publisher","first-page":"e7","DOI":"10.1017\/erm.2013.8","volume":"15","author":"T Yucel-Lindberg","year":"2013","unstructured":"Yucel-Lindberg T, Bage T . Inflammatory mediators in the pathogenesis of periodontitis. Expert Rev Mol Med 2013; 15: e7.","journal-title":"Expert Rev Mol Med"},{"key":"BFaps201719_CR30","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1902\/jop.2003.74.3.391","volume":"74","author":"DT Graves","year":"2003","unstructured":"Graves DT, Cochran D . The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol 2003; 74: 391\u2013401.","journal-title":"J Periodontol"},{"key":"BFaps201719_CR31","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1007\/s00204-015-1472-2","volume":"89","author":"EK Kim","year":"2015","unstructured":"Kim EK, Choi EJ . Compromised MAPK signaling in human diseases: an update. Arch Toxicol 2015; 89: 867\u201382.","journal-title":"Arch Toxicol"},{"key":"BFaps201719_CR32","doi-asserted-by":"publisher","first-page":"55","DOI":"10.2174\/138920009787048347","volume":"10","author":"KL Kirkwood","year":"2009","unstructured":"Kirkwood KL . Rossa C Jr . The potential of p38 MAPK inhibitors to modulate periodontal infections. Curr Drug Metab 2009; 10: 55\u201367.","journal-title":"Curr Drug Metab"},{"key":"BFaps201719_CR33","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/nchembio.1629","volume":"10","author":"A Chaikuad","year":"2014","unstructured":"Chaikuad A, Tacconi EM, Zimmer J, Liang Y, Gray NS, Tarsounas M, et al. A unique inhibitor binding site in ERK1\/2 is associated with slow binding kinetics. Nat Chem Biol 2014; 10: 853\u201360.","journal-title":"Nat Chem Biol"},{"key":"BFaps201719_CR34","doi-asserted-by":"publisher","first-page":"e510","DOI":"10.1038\/cddis.2013.14","volume":"4","author":"X Chen","year":"2013","unstructured":"Chen X, Hu C, Wang G, Li L, Kong X, Ding Y, et al. Nuclear factor-kappaB modulates osteogenesis of periodontal ligament stem cells through competition with beta-catenin signaling in inflammatory microenvironments. Cell Death Dis 2013; 4: e510.","journal-title":"Cell Death Dis"},{"key":"BFaps201719_CR35","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1111\/bju.12452","volume":"113","author":"DP Nguyen","year":"2014","unstructured":"Nguyen DP, Li J, Tewari AK . Inflammation and prostate cancer: the role of interleukin 6 (IL-6). BJU Int 2014; 113: 986\u201392.","journal-title":"BJU Int"},{"key":"BFaps201719_CR36","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1111\/j.1600-0757.2007.00213.x","volume":"44","author":"MS Reddy","year":"2007","unstructured":"Reddy MS . Reaching a better understanding of non-oral disease and the implication of periodontal infections. Periodontol 2000 2007; 44: 9\u201314.","journal-title":"Periodontol 2000"},{"key":"BFaps201719_CR37","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1111\/prd.12129","volume":"72","author":"FA Scannapieco","year":"2016","unstructured":"Scannapieco FA, Cantos A . Oral inflammation and infection, and chronic medical diseases: implications for the elderly. Periodontol 2000 2016; 72: 153\u201375.","journal-title":"Periodontol 2000"},{"key":"BFaps201719_CR38","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1902\/jop.2006.620001","volume":"77","author":"WA Soskolne","year":"2006","unstructured":"Soskolne WA . Re: Impact of local adjuncts to scaling and root planing in periodontal disease therapy: a systematic review. Bonito AJ, Lux L, Lohr KN (2005;76:1227-1236). J Periodontol 2006; 77: 323\u20134.","journal-title":"J Periodontol"},{"key":"BFaps201719_CR39","doi-asserted-by":"crossref","first-page":"155","DOI":"10.31887\/DCNS.2003.5.2\/rcasagrandetango","volume":"5","author":"R Casagrande Tango","year":"2003","unstructured":"Casagrande Tango R . Psychiatric side effects of medications prescribed in internal medicine. Dialogues Clin Neurosci 2003; 5: 155\u201365.","journal-title":"Dialogues Clin Neurosci"},{"key":"BFaps201719_CR40","first-page":"645727","volume":"2015","author":"S Chen","year":"2015","unstructured":"Chen S, Chen Y, Chen B, Cai YJ, Zou ZL, Wang JG, et al. Plumbagin ameliorates CCl4-induced hepatic fibrosis in rats via the epidermal growth factor receptor signaling pathway. Evid Based Complement Alternat Med 2015; 2015: 645727.","journal-title":"Evid Based Complement Alternat Med"},{"key":"BFaps201719_CR41","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1158\/1940-6207.CAPR-14-0231","volume":"8","author":"BB Hafeez","year":"2015","unstructured":"Hafeez BB, Fischer JW, Singh A, Zhong W, Mustafa A, Meske L, et al. Plumbagin inhibits prostate carcinogenesis in intact and castrated PTEN knockout mice via targeting PKC\u03b1, Stat3, and epithelial-to-mesenchymal transition markers. Cancer Prev Res (Phila) 2015; 8: 375\u201386.","journal-title":"Cancer Prev Res (Phila)"},{"key":"BFaps201719_CR42","doi-asserted-by":"publisher","first-page":"362","DOI":"10.4248\/BR201304007","volume":"1","author":"W Yan","year":"2013","unstructured":"Yan W, Tu B, Liu YY, Wang TY, Qiao H, Zhai ZJ, et al. Suppressive effects of plumbagin on invasion and migration of breast cancer cells via the inhibition of STAT3 signaling and down-regulation of inflammatory cytokine expressions. Bone Res 2013; 1: 362\u201370.","journal-title":"Bone Res"},{"key":"BFaps201719_CR43","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1111\/j.1600-051X.2004.00493.x","volume":"31","author":"RM Rodrigues","year":"2004","unstructured":"Rodrigues RM, Gon\u00e7alves C, Souto R, Feres-Filho EJ, Uzeda M, Colombo AP . Antibiotic resistance profile of the subgingival microbiota following systemic or local tetracycline therapy. J Clin Periodontol 2004; 31: 420\u20137.","journal-title":"J Clin Periodontol"}],"container-title":["Acta Pharmacologica Sinica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/aps201719.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/aps201719","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/aps.2017.19","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/aps201719.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T08:36:06Z","timestamp":1684398966000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/aps201719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,5,29]]},"references-count":43,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2017,8]]}},"alternative-id":["BFaps201719"],"URL":"https:\/\/doi.org\/10.1038\/aps.2017.19","relation":{},"ISSN":["1671-4083","1745-7254"],"issn-type":[{"value":"1671-4083","type":"print"},{"value":"1745-7254","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,5,29]]},"assertion":[{"value":"29 October 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 March 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 May 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}