{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T07:52:33Z","timestamp":1781596353964,"version":"3.54.5"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011447","name":"Science and Technology Department of Henan Province","doi-asserted-by":"publisher","award":["171100310500"],"award-info":[{"award-number":["171100310500"]}],"id":[{"id":"10.13039\/501100011447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Molecules"],"abstract":"<jats:p>Corydalis humosa Migo is a traditional Chinese medicine that clears away damp heat, relieves sore. Protopine (PRO) is an alkaloid component isolated from C. humosa Migo. However, the role of protopine in acute kidney injury (AKI) has not yet been reported. This study aims to investigate the effect and mechanism of protopine isolated from C. humosa Migo on lipopolysaccharide (LPS)-induced AKI in mice. Inflammation accumulation was assessed by small animal living imaging. The blood urea nitrogen (BUN), and serum creatinine (Scr) were measured to assess the effects of protopine on renal function in LPS-induced AKI. The levels of tumor necrosis factor (TNF), interleukin-2 (IL-2), interferon-\u03b3 (IFN-\u03b3), and (interleukin-10) IL-10 in serum were detected by cytometric bead array. Flow cytometry was used to detect the levels of reactive oxygen species (ROS) in primary kidney cells. The proportions of granulocytes, neutrophils, and macrophages in peripheral blood were examined to evaluate the effect of protopine on immune cells in mice with AKI. Toll-like receptor (TLR4) and apoptotic signaling pathway were detected by Western blot analysis. The results showed that protopine markedly improved the renal function, relieve inflammation, reversed inflammatory cytokines, transformed apoptosis markers, and regulated the TLR4 signaling pathway in mice with AKI induced by LPS. The protopine isolated from C. humosa Migo protected mice against LPS-induced AKI by inhibiting apoptosis and inflammation via the TLR4 signaling pathway, thus providing a molecular basis for a novel medical treatment of AKI.<\/jats:p>","DOI":"10.3390\/molecules25010015","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T03:23:12Z","timestamp":1577071392000},"page":"15","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":56,"title":["Protopine Protects Mice against LPS-Induced Acute Kidney Injury by Inhibiting Apoptosis and Inflammation via the TLR4 Signaling Pathway"],"prefix":"10.3390","volume":"25","author":[{"given":"Beibei","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengnan","family":"Zeng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxuan","family":"Kan","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benke","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiqi","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengchao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoke","family":"Zheng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weisheng","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou 450046, China"},{"name":"Collaborative Innovation Center for Respiratory Disease Diagnosis and Treatment &amp; Chinese Medicine Development of Henan Province, Zhengzhou 450046, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1790","DOI":"10.1016\/j.bbabio.2014.07.005","article-title":"Evidence of oxidative stress and mitochondrial respiratory chain dysfunction in an in vitro model of sepsis-induced kidney injury","volume":"1837","author":"Quoilin","year":"2014","journal-title":"Biochim. Et Biophys. Acta (BBA) - Bioenerg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"294","DOI":"10.5152\/TJAR.2014.83436","article-title":"Sepsis and Acute Kidney Injury. Turk","volume":"42","author":"Bilgili","year":"2014","journal-title":"J. Anesth. Reanim."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1056\/NEJMra032401","article-title":"Acute renal failure and sepsis","volume":"351","author":"Robert","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1681\/ASN.2010050484","article-title":"Sepsis and acute kidney injury","volume":"22","author":"Zarjou","year":"2011","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-1661-0_1","article-title":"Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis","volume":"1219","author":"Choudhary","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.freeradbiomed.2014.03.012","article-title":"Role of TLR4 in lipopolysaccharide-induced acute kidney injury: Protection by blueberry","volume":"71","author":"Nair","year":"2014","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1089\/sur.2015.184","article-title":"Persistent Inflammation, Immunosuppression, and Catabolism: Evolution of Multiple Organ Dysfunction","volume":"17","author":"Rosenthal","year":"2016","journal-title":"Surg. Infect."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"H2726","DOI":"10.1152\/ajpheart.00376.2007","article-title":"TNF-\u03b1-induced mitochondrial oxidative stress and cardiac dysfunction: Restoration by superoxide dismutase mimetic Tempol","volume":"293","author":"Mariappan","year":"2007","journal-title":"Am. J. Physiol. Circ. Physiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"F298","DOI":"10.1152\/ajprenal.90628.2008","article-title":"Chronic NF-kappaB blockade reduces cytosolic and mitochondrial oxidative stress and attenuates renal injury and hypertension in SHR","volume":"296","author":"Elks","year":"2009","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"252","DOI":"10.5114\/aoms.2015.48130","article-title":"Remote effect of kidney ischemia-reperfusion injury on pancreas: Role of oxidative stress and mitochondrial apoptosis","volume":"12","author":"Abogresha","year":"2016","journal-title":"Arch. Med. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"23975","DOI":"10.1038\/srep23975","article-title":"Metformin Protects Against Cisplatin-Induced Tubular Cell Apoptosis and Acute Kidney Injury via AMPK\u03b1-regulated Autophagy Induction","volume":"6","author":"Li","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"581","DOI":"10.2174\/092986708783769704","article-title":"Inflammatory markers in SIRS, sepsis and septic shock","volume":"15","author":"Renz","year":"2008","journal-title":"Curr. Med. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"42172","DOI":"10.18632\/oncotarget.9902","article-title":"TLR4\/ROS\/miRNA-21 pathway underlies lipopolysaccharide instructed primary tumor outgrowth in lung cancer patients","volume":"7","author":"Zhang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_14","first-page":"556","article-title":"Chemical Constituents from Corydalis humsoa","volume":"28","author":"Tao","year":"2005","journal-title":"Chin. Herb. Med."},{"key":"ref_15","first-page":"261","article-title":"Chemical constituents of Corydalis Humosa","volume":"20","author":"Liu","year":"1989","journal-title":"J. China Pharm. Univ."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"110583","DOI":"10.1016\/j.fct.2019.110583","article-title":"Protopine attenuates inflammation stimulated by carrageenan and LPS via the MAPK\/NF-\u03baB pathway","volume":"131","author":"Alam","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.vetpar.2010.03.032","article-title":"In vivo anthelmintic activity of five alkaloids from Macleaya microcarpa (Maxim) Fedde against Dactylogyrus intermedius in Carassius auratus","volume":"171","author":"Wang","year":"2010","journal-title":"Vet. Parasitol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.fitote.2010.06.020","article-title":"Phytochemical and antimicrobial characterization of Macleaya cordata herb","volume":"81","author":"Kosina","year":"2010","journal-title":"Fitoterapia"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.phymed.2007.11.010","article-title":"Hepatoprotective potential of Fumaria indica Pugsley whole plant extracts, fractions and an isolated alkaloid protopine","volume":"15","author":"Rathi","year":"2008","journal-title":"Phytomedicine"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3109\/10641955.2013.792346","article-title":"Coagulation\/Fibrinolysis and laboratory characteristics of pregnant women with severely depressed antithrombin activity","volume":"32","author":"Yamada","year":"2013","journal-title":"Hypertens. Pregnancy"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s40635-015-0057-y","article-title":"Scavenging reactive oxygen species using tempol in the acute phase of renal ischemia\/reperfusion and its effects on kidney oxygenation and nitric oxide levels","volume":"3","author":"Aksu","year":"2015","journal-title":"Intensiv. Care Med. Exp."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1177\/0310057X1304100207","article-title":"Is suppression of apoptosis a new therapeutic target in sepsis","volume":"41","author":"Harjai","year":"2013","journal-title":"Anaesth Intensive Care"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Uchida, T., Ito, S., Kumagai, H., Oda, T., Nakashima, H., and Seki, S. (2019). Roles of Natural Killer T Cells and Natural Killer Cells in Kidney Injury. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102487"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s00011-010-0268-3","article-title":"MnTMPyP, a superoxide dismutase\/catalase mimetic, decreases inflammatory indices in ischemic acute kidney injury","volume":"60","author":"Mortensen","year":"2011","journal-title":"Inflamm Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5817","DOI":"10.4049\/jimmunol.168.11.5817","article-title":"Acute renal failure in endotoxemia is caused by TNF acting directly on TNF receptor-1 in kidney","volume":"168","author":"Cunningham","year":"2002","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1161\/HYPERTENSIONAHA.119.13022","article-title":"TLR (Toll-Like Receptor) 4 Antagonism Prevents Left Ventricular Hypertrophy and Dysfunction Caused by Neonatal Hyperoxia Exposure in Rats","volume":"74","author":"Mian","year":"2019","journal-title":"Hypertension"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.intimp.2014.08.011","article-title":"TLR4 signaling: A potential therapeutic target in ischemic coronary artery disease","volume":"23","author":"Jia","year":"2014","journal-title":"Int. Immunopharmacol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Teo, J.D., Macary, P.A., and Tan, K.S. (2014). Pleiotropic effects of Blastocystis spp. Subtypes 4 and 7 on ligand-specific toll-like receptor signaling and NF-kappaB activation in a human monocyte cell line. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0089036"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4415","DOI":"10.3892\/mmr.2015.3925","article-title":"Rhein inhibits lipopolysaccharide-induced intestinal injury during sepsis by blocking the toll-like receptor 4 nuclear factor-kappaB pathway","volume":"12","author":"Zhang","year":"2015","journal-title":"Mol. Med. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/gm177","article-title":"Recent insights into the role of NF-kappaB in ovarian carcinogenesis","volume":"2","author":"Alvero","year":"2010","journal-title":"Genome Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/13813455.2017.1422766","article-title":"Chemoprotective effects of curcumin on doxorubicin-induced nephrotoxicity in wistar rats: By modulating inflammatory cytokines, apoptosis, oxidative stress and oxidative DNA damage","volume":"124","author":"Benzer","year":"2018","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/nri2725","article-title":"NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production?","volume":"10","author":"Tschopp","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1681\/ASN.2010020143","article-title":"The NLRP3 inflammasome promotes renal inflammation and contributes to CKD","volume":"21","author":"Vilaysane","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1146\/annurev.immunol.021908.132715","article-title":"The Inflammasomes: Guardians of the Body","volume":"27","author":"Martinon","year":"2009","journal-title":"Annu. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/S1074-7613(04)00046-9","article-title":"NALP3 Forms an IL-1\u03b2-Processing Inflammasome with Increased Activity in Muckle-Wells Autoinflammatory Disorder","volume":"20","author":"Laetitie","year":"2004","journal-title":"Immunity"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1615\/CritRevImmunol.2013008686","article-title":"The Inflammasome and Its Regulation","volume":"34","author":"Kohsuke","year":"2014","journal-title":"Crit. Rev. Immunol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/nature15514","article-title":"Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death","volume":"526","author":"Shi","year":"2015","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"Kayagaki","year":"2015","journal-title":"Nature"}],"updated-by":[{"DOI":"10.3390\/molecules31050806","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,12,19]],"date-time":"2019-12-19T00:00:00Z","timestamp":1576713600000}}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/1\/15\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T10:25:11Z","timestamp":1772447111000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/25\/1\/15"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,19]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,1]]}},"alternative-id":["molecules25010015"],"URL":"https:\/\/doi.org\/10.3390\/molecules25010015","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,19]]}}}