Author

Chi Chiu Wong

Year of Award

4-4-2019

Degree Type

Thesis

Degree Name

Master of Philosophy (MPhil)

Department

Department of Chemistry.

Principal Supervisor

Wong, Ka-Leung

Keywords

Cancer;Colon (Anatomy);Gynostemma pentaphyllum;Herbs;Therapeutic use;Treatment.

Language

English

Abstract

Gynostemma pentaphyllum (Thunb.) Makino, or called Jiaogulan (絞股藍), is a perennial creeping herb, which belongs to the Cucurbitaceae family. In China, it can be found in the South Shaanxi and the southern area of the Yangtze River. It is also widely distributed in Japan, India, Indo-China, and Indonesia. G. pentaphyllum is an herbal drug of diverse therapeutic effects without obvious toxic effects in the view of traditional Chinese medicine. Saponins extracted from G. pentaphyllum are most likely to be the main active ingredients for its various biological function and clinical effect. Over a hundred of saponins have been isolated and identified in G. pentaphyllum Gynostemma total saponins (GpS). Pharmacokinetics is one of the important concepts in pharmacology, which interested in relations among absorption, distribution, metabolism and excretion (ADME) of drug. The blood concentration of the drug is used to study the disposition of drugs and to monitor the progress of therapy. In this project, it aims to determinate the pharmacokinetic of total saponins extraction of G. pentaphyllum at a single oral dosage of 6 g/kg GpS in C57BL/6J wild type mice plasma by UPLC-MS analysis with the use of gypenoside III, IV, VIII, G, 20(S) and 20(R)-Rg3 as markers of total gypenosides. Method has been developed and validated for the quantification of GpS in plasma samples. Previous studies show that cancer cell may perform higher glucose uptake rate while producing lactic acid as final metabolite rather than undergoes the complete oxidation of pyruvate. Gp-VIII was chosen to be further studied regarding to the role of glycolic pathway. MTT assay were performed to determine the LD50 value of Gp-VIII in HCT116 cells. In onwards experiment, HCT116 cells were harvested in the presence of up to 250nM Gp-VIII. Reduction of glucose uptake was observed. Downregulation of different glycolic enzymes including aldolase, TPI, GAPDH, enolase, PKM2 and LDH were observed. Transcription factor HIF-1α was also found to be inhibited by Gp-VIII. Oral administration of 10mg/kg Gp-VIII in ApcMin/+ mice model was applied to investigate the inhibitory effect of polyp formation. Briefly, about 35% suppression of total number of polyp formation was observed in Gp-VIII treatment group. Number of polyps in different size of ≤ 2mm were reduced by 70%. Reduction of the number of polyps in different intestinal regions was observed with the greatest suppression effect in medial and distal of intestine.

Comments

Principal supervisor: Professor Wong Ka-Leung ; Thesis submitted to the Department of Chemistry ; Thesis (M.Phil.)--Hong Kong Baptist University, 2019.

Bibliography

Includes bibliographical references (pages 72-82).



Share

COinS