動脈硬化是一種脂質、發炎細胞及結締組織在主動脈壁的堆積且為一長期緩慢的漸進式發炎疾病，而巨噬細胞參與動脈硬化發展的過程。研究顯示山苦瓜能夠降低前發炎因子 PGE2及nitric acid（NO）的分泌。本研究主要探討山苦瓜乙酸乙酯萃取物 （ethyl acetate extract, EAE）、乙酸乙酯萃取物之皂化物 （Saponifiable substances, S）、不皂化物（Non-saponifiable sunstances, NS），對巨噬細胞發炎反應之抑制功效，使用2381及CK兩種山苦瓜的品種，結果分述如下：（一）2381EAE、2381NS及2381S都能減少NO的產生及iNOS的表現。2381EAE濃度達300 μg/ml時可降低TNF-α分泌，但2381NS及S則對TNF-α分泌沒有顯著影響。2381EAE或2381NS對IL-10分泌沒有影響，但2381S濃度達250 μg/ml及300 μg/ml時，IL-10分泌顯著低於僅LPS組。（二）CK-EAE（200~300 μg/ml）及CK-S（150 μg/ml）僅顯著減少NO產生及iNOS表現，而CK-NS 對NO、TNF-α、IL-10分泌及iNOS表現均無顯著影響。為探討苦瓜經體內代謝後，對巨噬細胞的影響，將2381EAE加入chow diet餵食老鼠，並採集血液進行實驗，以EAE-serum或baseline-serum培養巨噬細胞，NO、TNF-α的分泌及iNOS的表現沒有顯著差異，但EAE-Serum使巨噬細胞IL-10分泌顯著高於baseline-serum。先前研究發現苦瓜成分中capric acid可抑制巨噬細胞PGE2生成，conjugated linolenic acid （CLN）可活化PPAR-a，而fenofibrate為合成的PPAR-α配位體，故以此三純化學物進行實驗，與僅用LPS處理的細胞相比，fenofibrate、capric acid及CLN有降低 NO生成量的趨勢，但未達顯著。而iNOS的表現與僅用LPS處理比較皆有減少。對LPS誘發的TNF-α生成，Fenofibrate或 CLN的加入處理並沒有顯著影響，而capric acid則顯著高於僅LPS組。各組間IL-10的分泌沒有顯著差異。本研究結果顯示，山苦瓜萃取物確實能減少巨噬細胞的發炎反應，且經由體內代謝後的血清可以增加巨噬細胞IL-10的分泌。

Atherosclerosis is characterized by accumulation of lipids, inflammatory cell, and connective tissue within the arterial wall. It is a chronic, progressive disease with a long asymptomatic phage. Macrophages are involved in every phase of atherogenesis. Research suggests that wild bitter gourd decreases the release of pro-inflammatory mediator PGE2 and nitric oxide （NO）. The aim of this study was to investigate the effect of ethyl acetate extracts（EAE）of wild bitter gourd（Momordica charantia L.）, saponifiable substances of ethyl acetate（S）and nonsaponification of ethyl acetate（NS）on Lipopolysaccharide（LPS）-stimulated RAW 264.7 macrophages. The results showed（1）2381EAE, 2381NS and 2381S decreased NO production and iNOS expression in a dose-dependent manner（p＜0.05）.TNF-α production reduced significantly by 2381EAE（300 μg/ml）.There were no significant changes in TNF-α production with 2381NS or 2381S. IL-10 production was not changed by 2381EAE or 2381NS, but was significantly decreased by 2381S（250-300 μg/ml）（p＜0.05）.（2）CK-EAE（200 - 300 μg/ml）and CK-S（150 μg/ml）significantly decreased NO production and iNOS expression, but CK-NS did not. TNF-α and IL-10 releases were not significantly changed by CK extracts. To test the effect of bitter gourd in vivo metabolites on macrophages, serum samples（EAE serum）obtained from ICR mice fed diet containing 1.5% 2381EAE for 1 week were used to culture RAW 264.7 macrophage. The results showed that NO and TNF-α production were not significantly different between EAE-serum and baseline-serum treatments. But, IL-10 secretion increased significantly in macrophages cultured with EAE-serum（p＜0.05）. Capric acid and conjugated linolenic acid (CLN), identified from bitter gourd to be a PGE2 inhibitor of macrophage, and a PPAR-alpha activator, respectively, and fenofibrate, a well-known PPAR-alpha activator, were also investigated in this model. The results showed fenofibrate, capric acid and CLN decreased nitric oxide production without statistical significance, but the expression of iNOS was down regulated by all of them. TNF-α production in cells incubated with fenofibrate decreased by 26.5% while that with capric acid increased as compared with cells incubated with LPS alone. IL-10 productions were not significantly changed by fenofibrate, capric acid or CLN. In conclusion, the wild bitter gourd EAE decreases the productions of inflammatory mediator NO and TNF, and the bio-metabolites of bitter gourd EAE increase the production of anti-inflammatory mediator IL-10 in macrophages.

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