{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:11:49Z","timestamp":1780614709803,"version":"3.54.1"},"reference-count":24,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2008,12,18]],"date-time":"2008-12-18T00:00:00Z","timestamp":1229558400000},"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>During the last two decades triterpenes have attracted attention because of their pharmacological potential. Triterpene extract (TE) from outer bark of birch consisting mainly of betulin is able to form an oleogel which was successfully tested in the treatment of actinic keratosis. Some aspects of TE in vitro pharmacology are already known. Now we show preliminary pharmacokinetics of betulin and results of a subchronic toxicity study of TE in rats and dogs. Because of poor aqueous solubility of the TE-triterpenes (&lt; 0.1 \u03bcg\/mL respectively), for pharmacokinetic studies it was suspended in sesame oil (rats, i.p.) and PEG 400 \/ 0.9 % NaCl (dogs, s.c.). I.p. administered, betulin, the main component of TE, shows time dependency over a period of 4 h and reaches a dose-independent serum level of 0.13 \u03bcg\/mL. Dose dependency was observed with s.c. administration. At 300 mg\/kg a maximum plasma concentration of 0.33 \u03bcg\/mL betulin was detected after 28 daily applications. The subchronic toxicity study showed no toxicity of TE in rats (i.p.) and dogs (s.c.). In conclusion, triterpene extract from birch bark is safe, its betulin is bioavailable and in addition to published triterpene biological activities TE provides high potential for further pharmaceutical and pharmacological research.<\/jats:p>","DOI":"10.3390\/molecules13123224","type":"journal-article","created":{"date-parts":[[2008,12,18]],"date-time":"2008-12-18T08:42:13Z","timestamp":1229589733000},"page":"3224-3235","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":127,"title":["A Preliminary Pharmacokinetic Study of Betulin, the Main Pentacyclic Triterpene from Extract of Outer Bark of Birch (Betulae alba cortex)"],"prefix":"10.3390","volume":"13","author":[{"given":"Sebastian","family":"J\u00e4ger","sequence":"first","affiliation":[{"name":"Carl Gustav Carus-Institut, Am Eichhof 30, D-75223 Niefern-\u00d6schlbronn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie N.","family":"Laszczyk","sequence":"additional","affiliation":[{"name":"Carl Gustav Carus-Institut, Am Eichhof 30, D-75223 Niefern-\u00d6schlbronn, Germany"},{"name":"Betulin-Institut, Blumenstrasse 24, D-64297 Darmstadt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armin","family":"Scheffler","sequence":"additional","affiliation":[{"name":"Carl Gustav Carus-Institut, Am Eichhof 30, D-75223 Niefern-\u00d6schlbronn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2008,12,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1515\/hfsg.1983.37.4.205","article-title":"The suberin monomers and triterpenoids from the outer bark of betula verruosa ehrh","volume":"37","author":"Ekman","year":"1983","journal-title":"Holzforschung"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1055\/s-2006-951723","article-title":"Physical, chemical and pharmacological characterization of a new oleogel-forming triterpene extract from the outer bark of birch (betulae cortex)","volume":"72","author":"Laszczyk","year":"2006","journal-title":"Planta Med."},{"key":"ref_3","first-page":"588","article-title":"Protective effects of betulin and betulinic acid against ethanol-induced cytotoxicity in HepG2 cells","volume":"57","year":"2005","journal-title":"Pharmacol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1248\/cpb.54.535","article-title":"Ceanothane- and lupane-type triterpenes with antiplasmodial and antimycobacterial activities from Ziziphus cambodiana","volume":"54","author":"Suksamrarn","year":"2006","journal-title":"Chem. Pharm. Bull."},{"key":"ref_5","first-page":"359","article-title":"Betulinic acid: a promising anticancer candidate","volume":"7","author":"Eiznhamer","year":"2004","journal-title":"IDrugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jep.2005.05.024","article-title":"Oleanolic acid and ursolic acid: research perspectives","volume":"100","author":"Liu","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Alakurtti, S., Makela, T., Koskimies, S., and Yli-Kauhaluoma, J. Pharmacological properties of the ubiquitous natural product betulin. Eur. J. Pharm. Sci., 2006.","DOI":"10.1016\/j.ejps.2006.04.006"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0014-2999(97)01187-4","article-title":"Effect of selected triterpenoids on chronic dermal inflammation","volume":"334","author":"Manez","year":"1997","journal-title":"Eur. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/S0378-8741(01)00175-1","article-title":"Anti-inflammatory activity of lupeol and lupeol linoleate in rats","volume":"76","author":"Geetha","year":"2001","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1515\/znc-2000-9-1023","article-title":"Effect of minor components of virgin olive oil on topical antiinflammatory assays","volume":"55","year":"2000","journal-title":"Z. Naturforsch."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1002\/med.10053","article-title":"Chemistry, Biological Activity, and Chemotherapeutic Potential of Betulinic Acid for the Prevention and Treatment of Cancer and HIV Infections","volume":"24","author":"Cichewicz","year":"2004","journal-title":"Med. Res. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1211\/0022357021778718","article-title":"Gastroprotective activity of oleanolic acid derivatives on experimentally induced gastric lesions in rats and mice","volume":"54","author":"Astudillo","year":"2002","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0378-8741(95)90032-2","article-title":"Pharmacology of oleanolic acid and ursolic acid","volume":"49","author":"Liu","year":"1995","journal-title":"J. Ethnopharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/j.2042-7158.1992.tb03646.x","article-title":"Anti-inflammatory activity of oleanolic acid in rats and mice","volume":"44","author":"Singh","year":"1992","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1002\/1099-081X(199911)20:8<379::AID-BDD198>3.0.CO;2-C","article-title":"Pharmacokinetics and tissue distribution of betulinic acid in CD-1 mice","volume":"20","author":"Udeani","year":"1999","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1055\/s-2007-967106","article-title":"Solubility Studies of Oleanolic Acid and Betulinic Acid in Aqueous Solutions and Plant extracts of Viscum album L","volume":"73","author":"Winkler","year":"2007","journal-title":"Planta Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1002\/bdd.530","article-title":"Dose-linear pharmacokinetics of oleanolic acid after intravenous and oral administration in rats","volume":"28","author":"Jeong","year":"2007","journal-title":"Biopharm. Drug Dispos."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1023\/B:PHAM.0000016235.32639.23","article-title":"Solubilizing excipients in oral and injectable formulations","volume":"21","author":"Strickley","year":"2004","journal-title":"Pharm. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1111\/j.1610-0387.2006.05906.x","article-title":"Treatment of actinic keratoses with birch bark extract: a pilot study","volume":"4","author":"Huyke","year":"2006","journal-title":"J. Dtsch. Dermatol. Ges."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Huyke, C., Reuter, J., Rodig, M., Kersten, A., Laszczyk, M., Scheffler, A., Nashan, D., and Schempp, C. (2008). Treatment of actinic keratoses with a novel betulin-based oleogel. A prospective, randomized, comparative pilot study. J. Dtsch. Dermatol. Ges., Sep 19. [Epub].","DOI":"10.1111\/j.1610-0387.2008.06865.x"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1042\/bj2770521","article-title":"Inhibition of human leucocyte elastase by ursolic acid. Evidence for a binding site for pentacyclic triterpenes","volume":"277","author":"Ying","year":"1991","journal-title":"Biochem. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1002\/rcm.1155","article-title":"Quantitative analysis of betulinic acid in mouse, rat and dog plasma using electrospray liquid chromatography\/mass spectrometry","volume":"17","author":"Cheng","year":"2003","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/S0378-4347(99)00291-1","article-title":"Determination of betulinic acid in mouse blood, tumor and tissue homogenates by liquid chromatography-electrospray mass spectrometry","volume":"732","author":"Shin","year":"1999","journal-title":"J. Chromatogr. B"},{"key":"ref_24","first-page":"138","article-title":"A rapid method for the differential staining of blood films and malaria parasites","volume":"7","author":"Wright","year":"1902","journal-title":"J. Med. Res."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/13\/12\/3224\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:21:16Z","timestamp":1760221276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/13\/12\/3224"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,12,18]]},"references-count":24,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2008,12]]}},"alternative-id":["13123224"],"URL":"https:\/\/doi.org\/10.3390\/molecules13123224","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,12,18]]}}}