1st year：以LPS 活化之巨噬細胞為模式，透過分配萃取及管柱層析等化學分離的方式，追蹤山苦瓜中能抑制PGE2 合成的區分物，並進一步分離鑑定山苦瓜中具抗發炎能力之活性成分，並且探討其可能之作用機轉。
2nd year：採用直接注射定量的內毒素來誘導形成急性敗血症，再進一步觀察山苦瓜萃取物之給予所產生之營養生理方面的變化。
3rd year：採用盲腸結紥穿刺手術(CLP)，使動物產生腹膜炎而導致慢性敗血症，再進一步觀察山苦瓜萃取物之給予所產生之營養生理方面的變化。
本研究預期所篩選出來之山苦瓜萃取區分物可以透過PPARγ的活化並調控其標的基因之表現，進而降低由內毒素所誘發之初發炎細胞激素，減少經盲腸結紥穿刺所引發敗血症動物之死亡率。此新發現可供抗發炎保健食品之開發參考，以及臨床上敗血症治療之應用。
The mechanism of wild bitter gourd extracts on the anti-inflammatory effects and studies on the sepsis in experimental animal model
Our lab previously reported that the ethyl acetate extract of bitter gourd activated peroxisome proliferator-activated receptors (PPARs) α and γ. PPARγ has essential roles in adipogenesis and glucose homeostasis, and is a molecular target of insulin-sensitizing drugs. Although the ability of PPARγ agonists to antagonize inflammatory responses by transrepression of nuclear factor kappa B (NF-kB) target genes is linked to antidiabetic and antiatherogenic actions, the mechanisms remain poorly understood. We use the RAW264.7 cell line to trace and identify the bioactive compound that could inhibited PGE2 synthesis. The potential health benefits of bioactive compound from wild bitter gourd extracts through the PPARγ regulated mechanism are worthy to be further characterized in in vivo animal studies.
Sepsis, mainly caused by bacterial infection, is one of the major causes of death in clinical patients. More than 200,000 patients die of sepsis every year in the United States, and is the top 13 cause of death in Taiwan. However, no effective interventions in treating sepsis have been reported during past two decades. Two common septic models were used, lipopolysaccharide (LPS) and cecal ligation and puncture (CLP). Many researches of sepsis and clinical trials designed to improve the mortality of patients with sepsis. In recent years, LPS for inducing acute sepsis in conscious animals model has been apply to clinical condition. In chronic sepsis animal model, CLP model is used most frequently. On the other hand, to compare chronic sepsis model with acute sepsis model in differences of physiological and nutritional biochemistry changes. The aim of the study was to examine the effects and the possible mechanisms of wild bitter gourd extracts against sepsis. We hoped that wild bitter gourd extracts could attenuated multiple organ failure (MOF) and decreased the mortality in septic rats.
