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Studies on metabolism and pharmacological effect of active constituents of a Tibetan herbal medicine, halenia elliptica /cWong, Yan. / CUHK electronic theses & dissertations collection

Halenia elliptica D. Don belongs to Gentianaceae family. It is often used as part of a traditional Tibetan medicine to treat hepatitis. In the present investigation, six major xanthone components were isolated and identified from Halenia elliptica. An HPLC/DAD/APCI/MS method was developed and validated for the quantitative analysis of these xanthones, including 1-hydroxy-2,3,5-trimethoxy-xanthone (HM-1), 1-hydroxy-2,3,4,7-tetramethoxy- xanthone (HM-2), 1-hydroxy-2,3,4,5-tetramethoxy-xanthone (HM-3), 1,7- dihydroxy-2,3,4,5-tetramethoxy-xanthone (HM-4), 1,5-dihydroxy-2,3-dimethoxy-xanthone (HM-5) and 1-0-[beta-D-xylopyranosyl-(1-6)-beta-D-glucopyranosyl]-2,3,5-trimethoxy-xanthone (HM-2-10). All the xanthones aglycons caused vasodilation in the coronary artery pre-contracted with 1 muM 5-HT, but the xanthone glycoside had no effect. HM-1 was one of the most abundant xanthones with the most potent vasorelaxant activity. / Mechanisms of the vasorelaxant effect of HM-1 were investigated. HM-1 showed a potent vasorelaxant activity on rat coronary artery involved both an endothelium-dependent mechanism involving NO and an endothelium-independent mechanism by inhibiting Ca2+ influx through L-type voltage-operated Ca2+ channels. / Taken together, in spite of the pharmacokinetics results showed that HM-1 was rapidly and widely distributed to tissues after intravenous administration in rats, with conjugation to being the major metabolic pathway in vivo, both HM-1 and its active metabolite (HM-5) show that they are important pharmacological agents with potentially useful therapeutic indications. / The metabolism and pharmacokinetics of HM-1 displayed biphasic elimination kinetics, with an elimination half-life of 60.4 +/- 4.2 min. Four other Phase I metabolites were isolated and identified as demethylated products in vitro. HM-1 was metabolised to HM-5 in the liver. Biliary excretion studies showed that both HM-1 and the metabolite (HM-5) underwent extensive phase II conjugation to form glucuronides and sulfates. Tissue distribution studies showed that HM-1 was widely distributed to different organs. Collection of urine and faeces over 24 h showed that 10.88% of dose was excreted from urine and 1.91% of dose via faeces. / With HM-5 being one of the major in vivo metabolites of HM-1, the effect of HM-5 has been studied on rat coronary artery and compared to HM-1. HM-5-mediated vasorelaxant effect was mediated through opening of potassium channel (TEA, 4-AP) and altering intracellular calcium by partial inhibition of Ca2+ influx through L-type voltage-operated Ca 2+ channels and intracellular Ca2+ stores. / "September 2007." / Source: Dissertation Abstracts International, Volume: 69-08, Section: B, page: 4699. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2007. / Includes bibliographical references (p. 195-218). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Identiferoai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_344155
Date January 2007
ContributorsWang, Yan, Chinese University of Hong Kong Graduate School. Division of Chinese Medicine.
Source SetsThe Chinese University of Hong Kong
LanguageEnglish, Chinese
Detected LanguageEnglish
TypeText, theses
Formatelectronic resource, microform, microfiche, 1 online resource (xxiii, 218 p. : ill.)
CoverageChina, Tibet Autonomous Region, Tibet
RightsUse of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/)

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