{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T23:13:19Z","timestamp":1770505999690,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2012,5,25]],"date-time":"2012-05-25T00:00:00Z","timestamp":1337904000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cantharidin, an active component in mylabris, is used in traditional Chinese medicine (TCM) to treat scabies and hepatoma, but accompanied by hemorrhagic cystitis. Evidence shows that cantharidin induces human bladder carcinoma cell death through COX-2 overexpression in vitro. In TCM, Scutellaria baicalensis is usually used to cure mylabris-induced hematuria. This work was undertaken to determine the mechanisms of cantharidin-induced rat hemorrhagic cystitis and explore the uroprotective effect of S. baicalensis. In vitro results showed cantharidin could induce cytotoxicity through prostaglandin (PG)E2 overproduction of T24 cells. Boiling-water extract of S. baicalensis (SB-WE) could significantly inhibit PGE2 production and COX-2 expression in lipo-polysaccharide-induced RAW 264.7 cells, indicating obvious anti-inflammatory abilities. In vivo results indicated that cantharidin caused rat hemorrhagic cystitis with hematuria via c-Fos and COX-2 overexpression. SB-WE was given orally to cantharidin-treated rats, whereby hematuria level, elevated PGE2 and COX-2 protein overexpression were significantly and dose-dependently inhibited by SB-WE. The anti-inflammatory components of SB-WE are baicalin and wogonin, whose contents were 200.95 \u00b1 2.00 and 31.93 \u00b1 0.26 \u03bcg\/mg, respectively. In conclusion, cantharidin induces rat cystitis through c-Fos and COX-2 over-expression and S. baicalensis can prevent the resulting hematuria because of its anti-inflammatory effects.<\/jats:p>","DOI":"10.3390\/molecules17066277","type":"journal-article","created":{"date-parts":[[2012,5,25]],"date-time":"2012-05-25T11:15:22Z","timestamp":1337944522000},"page":"6277-6289","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Scutellaria baicalensis Alleviates Cantharidin-Induced Rat Hemorrhagic Cystitis through Inhibition of Cyclooxygenase-2 Overexpression"],"prefix":"10.3390","volume":"17","author":[{"given":"Steven Kuan-Hua","family":"Huan","sequence":"first","affiliation":[{"name":"Division of Urology, Department of Surgery, Chi Mei Medical Center, No.21, Taikang, Liuying Dist., Tainan City 73657, Taiwan"},{"name":"Graduate Institute of Clinical Medical Research, Taipei Medical University, 250 Wu-Hsing Street, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kun-Teng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei City 11031, Taiwan"},{"name":"Section of Biologics & Advanced Therapeutic Product Analysis, Division of Research and Analysis, Food and Drug Administration, No.161-2, Kunyang St, Nangang District, Taipei City 11561, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shauh-Der","family":"Yeh","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medical Research, Taipei Medical University, 250 Wu-Hsing Street, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Jung","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Chun","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Der-Zen","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate Institute of Biomedical Materials, Taipei Medical University, 250 Wu-Hsing Street, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ching-Chiung","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Pharmacy, College of Pharmacy, Taipei Medical University, 250 Wu-Hsing Street, Taipei City 11031, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2012,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1177\/096032719000900108","article-title":"Post-mortem serum concentration of cantharidin in a fatal case of cantharides poisoning","volume":"9","author":"Hundt","year":"1990","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"392","DOI":"10.2174\/1871520610909040392","article-title":"The effects of cantharidin and cantharidin derivates on tumour cells","volume":"9","author":"Liu","year":"2009","journal-title":"Anticancer Agents Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0006-291X(87)91607-X","article-title":"Cantharidin poisoning associated with specific binding site in liver","volume":"149","author":"Graziano","year":"1987","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/S0735-6757(96)90158-8","article-title":"Poisoning from \u201cSpanish fly\u201d (cantharidin)","volume":"14","author":"Karras","year":"1996","journal-title":"Am. J. Emerg. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.tox.2006.03.012","article-title":"Cantharidin-induced cytotoxicity and cyclooxygenase 2 expression in human bladder carcinoma cell line","volume":"223","author":"Huan","year":"2006","journal-title":"Toxicology"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/0378-8741(89)90062-7","article-title":"Medical uses of mylabris in ancient China and recent studies","volume":"26","author":"Wang","year":"1989","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1159\/000457561","article-title":"Induction of hepatic bilirubin and drug metabolizing enzymes by individual herbs present in the traditional Chinese medicine, yin zhi huang","volume":"20","author":"Yin","year":"1993","journal-title":"Dev. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1016\/S0024-3205(00)00864-X","article-title":"A comparison of human immunodeficiency virus type-1 protease inhibition activities by the aqueous and methanol extracts of Chinese medicinal herbs","volume":"67","author":"Lam","year":"2000","journal-title":"Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1055\/s-2002-23143","article-title":"Evaluation of the anti-inflammatory effect of baicalein on dextran sulfate sodium-induced colitis in mice","volume":"68","author":"Hong","year":"2002","journal-title":"Planta Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1023\/B:DDAS.0000020490.34220.6d","article-title":"Preventive effect of the flavonoid, wogonin, against ethanol-induced gastric mucosal damage in rats","volume":"49","author":"Park","year":"2004","journal-title":"Dig. Dis. Sci."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.jep.2006.03.030","article-title":"Pharmacokinetic comparisons of Shuang-Huang-Lian with the different combinations of its constitutional herbs","volume":"107","author":"Di","year":"2006","journal-title":"J. Ethnopharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"10934","DOI":"10.1021\/jf202741x","article-title":"Study of the chemical composition and antimicrobial activities of ethanolic extracts from roots of Scutellaria baicalensis Georgi","volume":"59","author":"Lu","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1111\/j.2042-7158.1997.tb06119.x","article-title":"Effects of flavonoids isolated from scutellariae radix on the production of tissue-type plasminogen activator and plasminogen activator inhibitor-1 induced by thrombin and thrombin receptor agonist peptide in cultured human umbilical vein endothelial cells","volume":"49","author":"Kimura","year":"1997","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1248\/cpb.51.339","article-title":"Novel synthesis of flavonoids of Scutellaria baicalensis Georgi","volume":"51","author":"Huang","year":"2003","journal-title":"Chem. Pharm. Bull. (Tokyo)"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1142\/S0192415X96000050","article-title":"The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin","volume":"24","author":"Lin","year":"1996","journal-title":"Am. J. Chin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1570-0232(04)00545-8","article-title":"Separation methods used for Scutellaria baicalensis active components","volume":"812","author":"Li","year":"2004","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.plefa.2004.04.009","article-title":"Suppression of cyclooxygenase-2 expression of skin fibroblasts by wogonin, a plant flavone from Scutellaria radix","volume":"72","author":"Chi","year":"2005","journal-title":"Prostaglandins Leukot. Essent. Fatty Acids"},{"key":"ref_18","first-page":"573","article-title":"Determination of baicalin and chlorogenic acid in yinhuang granule by capillary electrophoresis","volume":"17","author":"Yang","year":"1990","journal-title":"Se Pu"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"149","DOI":"10.5213\/inj.2010.14.3.149","article-title":"Expression of nitric oxide synthase and aquaporin-3 in cyclophosphamide treated rat bladder","volume":"14","author":"Cho","year":"2010","journal-title":"Int. Neurourol. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s00280-010-1392-z","article-title":"Cyclooxygenase-2 contributes to functional changes seen on experimental hemorrhagic cystitis induced by ifosfamide in rat urinary bladder","volume":"67","author":"Macedo","year":"2011","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_21","first-page":"4037","article-title":"Inhibition of cancer cell proliferation and prostaglandin E2 synthesis by Scutellaria baicalensis","volume":"63","author":"Zhang","year":"2003","journal-title":"Cancer Res."},{"key":"ref_22","first-page":"216","article-title":"Clinical toxicology: Part II. Diagnosis and management of uncommon poisonings","volume":"4","author":"Worthley","year":"2002","journal-title":"Crit. Care Resusc."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"505","DOI":"10.2165\/00148581-200305080-00001","article-title":"Pediatric molluscum contagiosum: Optimal treatment strategies","volume":"5","author":"Silverberg","year":"2003","journal-title":"Paediatr. Drugs"},{"key":"ref_24","first-page":"258","article-title":"Cantharidin Poisoning due to Blister Beetle Ingestion in Children: Two case reports and a review of clinical presentations","volume":"10","author":"Shabana","year":"2010","journal-title":"Sultan Qaboos Univ. Med. J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1542\/peds.98.3.458","article-title":"Ingestion of a blister beetle (Mecoidae family)","volume":"98","author":"Mallari","year":"1996","journal-title":"Pediatrics"},{"key":"ref_26","first-page":"187","article-title":"The endogenous cannabinoid, anandamide, induces COX-2-dependent cell death in apoptosis-resistant colon cancer cells","volume":"37","author":"Patsos","year":"2010","journal-title":"Int. J. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4103\/0019-509X.25769","article-title":"Comparison of uroprotective efficacy of mesna and amifostine in Cyclophosphamide-induced hemorrhagic cystitis in rats","volume":"43","author":"Kanat","year":"2006","journal-title":"Indian J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1007\/s002800050594","article-title":"Urinary excretion of ifosfamide, 4-hydroxyifosfamide, 3- and 2-dechloroethylifosfamide, mesna, and dimesna in patients on fractionated intravenous ifosfamide and concomitant mesna therapy","volume":"39","author":"Kurowski","year":"1997","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0924-8579(03)00084-0","article-title":"Production and resolution of cantharidin-induced inflammatory blisters","volume":"22","author":"Maglio","year":"2003","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"PL119","DOI":"10.1016\/0024-3205(94)90011-6","article-title":"Effects of CGRP in different models of mouse ear inflammation","volume":"54","author":"Clementi","year":"1994","journal-title":"Life Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3116","DOI":"10.1016\/j.fct.2008.06.084","article-title":"Liposome encapsulation reduces cantharidin toxicity","volume":"46","author":"Chang","year":"2008","journal-title":"Food Chem. Toxicol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.toxicon.2011.10.002","article-title":"Possible cantharidin poisoning of a great bustard (Otis tarda)","volume":"59","author":"Camarero","year":"2012","journal-title":"Toxicon"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2371","DOI":"10.1271\/bbb.50698","article-title":"Antioxidative and anti-inflammatory activities of polyhydroxyflavonoids of Scutellaria baicalensis GEORGI","volume":"70","author":"Huang","year":"2006","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wang, K.T., Chen, L.G., Chou, D.S., Liang, W.L., and Wang, C.C. (2011). Anti-oxidative abilities of essential oils from Atractylodes ovata rhizome. Evid. Based Complement. Alternat. Med.","DOI":"10.1093\/ecam\/neq006"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1021\/jf104718g","article-title":"Anti-inflammatory effects of resveratrol and oligostilbenes from Vitis thunbergii var. taiwaniana against lipopolysaccharide-induced arthritis","volume":"59","author":"Wang","year":"2011","journal-title":"J. Agric. Food Chem."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/17\/6\/6277\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:50:28Z","timestamp":1760219428000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/17\/6\/6277"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,5,25]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2012,6]]}},"alternative-id":["molecules17066277"],"URL":"https:\/\/doi.org\/10.3390\/molecules17066277","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,5,25]]}}}