Systems Biology Study on the Heart Protective and Anti- Heart Failure Efficacies of Chinese Medicinal Herbs
| Autor: | Hsin-Ying Tsai, 蔡欣穎 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 Backgrounds: Heart failure is a serious health problem that has no cure. With the increase of aging population, the incidence of cardiovascular disease is also increasing. However, the mechanism leading to heart failure is complex and is less understood. Chinese medicinal formula TNU-1 has been used in Taiwan for several decades for the invigoration of blood circulation and the elimination of stasis. Therefore, we proposed that TNU-1 might have a great impact on cardiovascular-related functions. In this study, we applied systems biology approaches to prove our speculation. Materials and Methods: Transgenic mice, which carried the luciferase gene driven by nuclear factor-κB (NF-κB), were administered orally with TNU-1 and its ingredients, and imaged for NF-κB activities in organs. Gene expression profiling induced by TNU-1 was analyzed by microarray analysis. Solvent partition of ingredients were prepared to identify the active components of TNU-1. Results: Bioluminescent imaging showed that oral administration of TNU-1 significantly affected NF-κB activity in left atria. Microarray analysis showed that the expression of sarcolipin, a novel regulator of cardiac sarcoplasmic reticulum Ca2+ ATPase 2a, was downregulated by TNU-1 and one of the ingredient of TNU-1, Carthamus tinctorius. Most relevant networks analysis showed that TNU-1 might decrease the expression of cytokine genes via suppression NF-κB activity and, in turn, inhibit the apoptotic pathways. We further investigated the potential protective effects of TNU-1, C. tinctorius, and its major bioactive compound hydroxy safflor yellow A on doxorubicin-induced cardiotoxicity. Data showed that hydroxy safflor yellow A treatment significantly inhibited doxorubicin-induced apoptosis via tumor necrosis factor-α death-receptor-dependent pathway and the downregulation of apoptotic proteins caspase 8 and caspase 3. Conclusion: We have found that a Chinese medicinal formula TUN-1 might target to sarcolipin gene and subsequently stimulate the cardiac contraction. In addition, hydroxy safflor yellow A may have the potential to prevent the complications of cardiotoxicity induced by doxorubicin in cancer chemotherapy. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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