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postgraduate thesis: Mechanism of action of Xinmailong, a proprietary Chinese medicine for the treatment of chronic heart failure

TitleMechanism of action of Xinmailong, a proprietary Chinese medicine for the treatment of chronic heart failure
Authors
Issue Date2014
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Cheung, C. [張俊]. (2014). Mechanism of action of Xinmailong, a proprietary Chinese medicine for the treatment of chronic heart failure. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5388013
AbstractChronic heart failure is one of the commonest fatal diseases in the world. Much work has been done to reveal its complicated pathogenesis and develop effective therapy. Xinmailong (XML), a compound extracted from Periplaneta americana, has been launched on the market in Mainland China as a proprietary medication for treating patients with chronic heart failure. Although it is highly effective, its mechanism of action is still not completely understood. In this study, the results of calcium (〖Ca〗^(2+)) imaging demonstrated that XML increased electrical impulse-induced intracellular calcium ([〖Ca〗^(2+)]i), in H9c2 cells, an rat embryonic cardiomyocytes cell line. This effect was dependent on extracellular 〖Ca〗^(2+) but not the 〖Ca〗^(2+) store from sarcoplasmic reticulum because XML had no effect on thapsigargin -induced 〖Ca〗^(2+) release. The effect of XML was inhibited by ML218-HCl but not nimodipine, indicating that XML interacted with T-type 〖Ca〗^(2+) channels but not L-type 〖Ca〗^(2+) channels. Unlike KB-R7943, which is a sodium calcium exchanger inhibitor, XML did not affect [〖Ca〗^(2+)]i in the absence of electric stimulation, implying that XML did not work on sodium calcium exchanger. Ouabain, a sodium-potassium ATPase inhibitor, increased the electrical impulse-induced [〖Ca〗^(2+)]i and the effect of ouabain and XML were not additive, suggesting that the site of action of ouabain and XML was overlapped. Biochemical assay on phosphate concentration showed that XML was able to inhibit the activity of sodium-potassium ATPase. Our study also demonstrated that XML reduced the production of reactive oxygen species in H9c2 cells. Western blotting showed that such antioxidant properties mechanism might involve the increased expressions of antioxidant enzymes including superoxide dismutase 1, superoxide dismutase 2 and heme oxygenase 1. In conclusion, our study has provided evidence that XML increases [〖Ca〗^(2+)]i level by activating T-type 〖Ca〗^(2+) channels and inhibiting sodium-potassium ATPase. The antioxidant effect of XML may also contribute to the cardioprotective effect of XML but further investigation is required.
DegreeMaster of Philosophy
SubjectCockroaches - Therapeutic use
Heart failure - Treatment
Dept/ProgramPharmacology and Pharmacy
Persistent Identifierhttp://hdl.handle.net/10722/208582

 

DC FieldValueLanguage
dc.contributor.authorCheung, Chun-
dc.contributor.author張俊-
dc.date.accessioned2015-03-13T01:44:01Z-
dc.date.available2015-03-13T01:44:01Z-
dc.date.issued2014-
dc.identifier.citationCheung, C. [張俊]. (2014). Mechanism of action of Xinmailong, a proprietary Chinese medicine for the treatment of chronic heart failure. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5388013-
dc.identifier.urihttp://hdl.handle.net/10722/208582-
dc.description.abstractChronic heart failure is one of the commonest fatal diseases in the world. Much work has been done to reveal its complicated pathogenesis and develop effective therapy. Xinmailong (XML), a compound extracted from Periplaneta americana, has been launched on the market in Mainland China as a proprietary medication for treating patients with chronic heart failure. Although it is highly effective, its mechanism of action is still not completely understood. In this study, the results of calcium (〖Ca〗^(2+)) imaging demonstrated that XML increased electrical impulse-induced intracellular calcium ([〖Ca〗^(2+)]i), in H9c2 cells, an rat embryonic cardiomyocytes cell line. This effect was dependent on extracellular 〖Ca〗^(2+) but not the 〖Ca〗^(2+) store from sarcoplasmic reticulum because XML had no effect on thapsigargin -induced 〖Ca〗^(2+) release. The effect of XML was inhibited by ML218-HCl but not nimodipine, indicating that XML interacted with T-type 〖Ca〗^(2+) channels but not L-type 〖Ca〗^(2+) channels. Unlike KB-R7943, which is a sodium calcium exchanger inhibitor, XML did not affect [〖Ca〗^(2+)]i in the absence of electric stimulation, implying that XML did not work on sodium calcium exchanger. Ouabain, a sodium-potassium ATPase inhibitor, increased the electrical impulse-induced [〖Ca〗^(2+)]i and the effect of ouabain and XML were not additive, suggesting that the site of action of ouabain and XML was overlapped. Biochemical assay on phosphate concentration showed that XML was able to inhibit the activity of sodium-potassium ATPase. Our study also demonstrated that XML reduced the production of reactive oxygen species in H9c2 cells. Western blotting showed that such antioxidant properties mechanism might involve the increased expressions of antioxidant enzymes including superoxide dismutase 1, superoxide dismutase 2 and heme oxygenase 1. In conclusion, our study has provided evidence that XML increases [〖Ca〗^(2+)]i level by activating T-type 〖Ca〗^(2+) channels and inhibiting sodium-potassium ATPase. The antioxidant effect of XML may also contribute to the cardioprotective effect of XML but further investigation is required.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshCockroaches - Therapeutic use-
dc.subject.lcshHeart failure - Treatment-
dc.titleMechanism of action of Xinmailong, a proprietary Chinese medicine for the treatment of chronic heart failure-
dc.typePG_Thesis-
dc.identifier.hkulb5388013-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePharmacology and Pharmacy-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5388013-

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