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UM E-Theses Collection (澳門大學電子學位論文庫)

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Title

Urinary and secondary metabolomic insights into gut microbiota

English Abstract

As the major active ingredients of ginsengs, ginsenosides possess extensive protective effects on cardiovascular diseases based on their potent regulatory capacity on oxidation, cell death, lipid metabolism, and, in particular, inflammation. According to positions of sugar moieties in the sapogenin skeleton, ginsenosides can be divided into two major sub-categories, i.e., 20 (S)-protopanaxadiol saponins (PDS) and 20 (S)-protopanaxatriol saponins (PTS). Ginsenoside Rb1 and Rg1 represent the most abundant ingredients of PDS and PTS, respectively, in Panax notoginseng and possesses potential benefits on ameliorating inflammatory responses, blunting cell apoptosis, and maintaining cell metabolic homeostasis. However, the roles of ginsenoside Rb1 and Rg1 in hepatic ischemia/reperfusion (I/R) injury and abdominal aortic aneurysm (AAA) remain largely unknown. In this thesis, we evaluated functions and latent mechanisms of ginsenoside Rg1 and Rb1 on hepatic I/R injury and AAA. The observations are summarized as below: 1) Ginsenoside Rg1 treatment significantly blocked I/R-induced liver dysfunction, tissue damage, inflammation, and cell death in mice. 2) The protective effect of ginsenoside Rg1 on hepatocytes was confirmed in isolated primary hepatocytes stimulated by LPS, whereas ginsenoside Rb1 exhibited cytotoxicity on primary hepatocytes. 3) The regulatory effect of ginsenoside Rg1 on I/R-induced liver damage was largely dependent on the inactivation of JNK/MAPK signaling. v 4) Ginsenoside Rb1, but not ginsenoside Rg1, significantly reduced AAA incidence, extracellular matrix (ECM) degradation, matrix metalloproteinase (MMP) production, inflammatory cell infiltration, and vascular smooth muscle cell (VSMC) dysfunction induced by angiotensin II (Ang II) for continuous 28 days. 5) The inhibitory effect of ginsenoside Rb1 on AAA progress was closely associated with inactivation of JNK and p38 MAPK signaling. In conclusion, using both in vivo and in vitro experiments, the present study demonstrated the beneficial effect of ginsenoside Rg1 and Rb1 on hepatic I/R injury and AAA, respectively, suggesting the potential therapeutic application of ginsenosides in the treatment of these pathologies and other related diseases. Furthermore, the difference of ginsenoside Rg1 and Rb1 on I/R injury and AAA indicated a context-specific function of PDS and PTS, which needs further investigations.

Issue date

2015.

Author

Yan, Zhi Xiang,

Faculty

Institute of Chinese Medical Sciences

Degree

Ph.D.

Subject

Molecular microbiology

Supervisor

燕茹

Files In This Item

Full-text (Internet)

Location
1/F Zone C
Library URL
991001805639706306