Dissertation > Medicine, health > Chinese Medicine > Of Pharmacy > Pharmacology

Evaluation Research on the Effective Chemomics and Mechanism Action of Zhikechuanbeipipa Dropping Pills

Author DongLinYi
Tutor ZhangZuoHui
School Tianjin University
Course Applied Chemistry
Keywords CBPP Quality Control Effective Chemome Compatibility Metabolomics UPLC/Q-TOF MS
CLC R285
Type PhD thesis
Year 2012
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Chuanbeipipa dropping pills(CBPP), a traditional Chinese medicine, consistingof Eriobotrya japonica leaf, Platycodon grandiflorum, Pinellia ternate, Fritillariaussuriensis and volatile oilextracts from Menthahaplocalyxis exclusively developedby employing modern technology. CBPP is widely used in clinicalon the treatment ofchronic obstructive lung disease and cough caused by bronchial catarrh, whichpossesses the advantage of small dosage, convenience, high bioavailability, littlegastrointestinal irritation, toxic and side-effect. However, the limited acknowledgmentof its chemical material basis and mechanism of action resisted theinternationalization of traditionalChinese medicine. And a holistic methodology,chemomics-integrated global systems biology, was performed to study on the globalchemome and mechanism appreciation to solve the problem above.Quality control: a rapid and comprehensive fingerprint method was establishedby using the UPLC/Q-TOF mass spectrum and six index components were analyzedquantitatively. And partial least squares discriminant analysis (PLS-DA) was appliedto quality assessment of diverse batches of CBPPs. The scores plot clearly revealedthe volatile oil was the key point of quality control. GC×GC-TOF-MAStechnique wasalso used to comprehensively analyze the sample batches of CBPPs.Validity assessment: CBPPs were extracted consequencely of dichloromethane,ethyl acetate, and butanol. Screening for effective compounds and assessment ofpharmacodynamics was respectivelyon the model of citric acid-induced coughing inguinea pigs, the concentration-response curves of acetylcholine chloride (ACh) aswell as bypGL4/NF-κB luciferase reporter vectors assay. The main bioactivecomponents of the DME were identified and analyzedto have effects on cough andasthma, meanwhile, butanolextract (BUE) was conformed anti inflammatory activities.A new technic bioinformatics researches in regulatory networks conjunct with onlinecell screening was also applied.Safety evaluation: The absorbable compounds were profiled by using threecomplementary: a computational prediction method in silico, a Caco-2cell monolayerin vitro experiment and an improved everted gut sac in vitro experiment. While themetabolites of CBPP, collected from serum, urine and feces afteroral administation in rat in vivo experiment, were analyzed by fingerprint methods. The current study aimed to establish a reliable and effective method for screeningthe potentially bioactive components of CBPP, report for the first time the basis ofCBPP pharmacology, and provide useful information for further studies on the CBPPmechanism of action.

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