Identify and Characterize the extracts of Eclipta alba and Cibotium barometz that can inhibit CDK5-mediated PPAR-γ phosphorylation

• Main Authors: Elfratiwy Saragih, 帝維
• Other Authors: Ming-Ko Chiang
• Format: Others
• Language: en_US
• Published: 2019
• Online Access: http://ndltd.ncl.edu.tw/handle/469h5j

碩士 === 國立中正大學 === 生命科學系分子生物研究所 === 107 === Type II Diabetes Mellitus (T2DM), caused by insulin resistance, is a world wide health concern. Thiazolidendiones (TZDs), insulin sensitizers, work by targeting PPAR-gamma phosphorylation. Unfortunately, they also promote adipocyte differentiation and weight gain and may cause adverse side effects, including fluid retention and heart failure. Nevertheless, several studies showed that thiazolidinediones have several undesirable side effects, including weight gain and heart failure. Troglitazone, a member of TZDs, has been withdrawn from the market due to its serious hepatotoxicity. Recently, researchers have been searching for medicines that could exhibit the same effects of TZDsthat would not cause any side effects such as weight gain and heart failure. To shed light on the aforementioned points, I investigated the potency of four Chinese medicines’ extracts to inhibit the PPAR-γ phosphorylation through in vitro kinase assay. The extracts include Ecliptae alba, Cibotium barometz, Glycyrrhizaeuralensis, and Liguisticum chuanxiong. These herbs have been used to treat some diseases such as cancer, blood cholesterol also inflammation. In addition, previous data in our lab showed that these extracts could inhibit the phosphorylation of PPAR-γ. The in vitro kinase assay for this primary extract showed that Ecliptaealba and Cibotium barometz worked better to inhibit the phosphorylation of PPAR-γ than the IV other two extracts of Glycyrrhiza euralensis sand Liguisticum chuanxiong. Therefore, based on the in vitro kinase assay result, I have extracted and separated different compounds of Ecliptae alba and Cibotium barometz using HPLC. Moreover, I determined which fractions of the medicines are effective on inhibiting the PPAR-γ phosphorylation through the in vitro kinase assay. Furthermore, the fraction with the capability to inhibit the phosphorylation of PPAR-γ was collected and used in 3T3 L1-cell differentiation model to verify its effect on adipogenesis. Ultimately, these extracts were also used to treat the primary hepatocytes of mice.