Atherosclerosis, the main cause of morbidity and mortality in developed countries, is now considered as a chronic inflammatory vascular disease. Many pathophysiologic studies have shown that the first step in its development and the most important events in inflammation is adhesion of monocytes to the vascular endothelium and their subsequent migration into the vessel wall. The activation of endothelial cells and resulting expression of adhesion molecules at sites of inflammation are of particular significance. Thus, the molecules that block these interactions have been targeted as potential therapeutic treatments for acute and chronic inflammatory diseases. Stillene compounds are present naturally in many plants, whose extensive biological activities have been identified. In recent years, the biological activites of stilbene compounds have been reported, including antioxidation, antitumor and anti-thrombotic action. Resveratrol (trans-3,5,4'-trihydroxystilbene), one of the most important and common stilbene compounds from Polygonum cuspidatum, as an important polyphenolic phytoalexin, exhibits beneficial effects to health, such as anti-cancer, cardioprotection, neuroprotection, anti-aging and anti-inflammation as shown in previous studies. And a large body of evidences point to a prominent role of resveratrol as an anti atherosclerotic agent. Previous studies showed that resveratrol analogues could have the similar but also differential and even opposing biological activities. Thus, this study is to investigate whether resveratrol analogues such as trans-3, 5, 4'-trimethoxystilbene (TMS) and polydatin have anti-inflammatory vascular effect and elucidate the mechanism of this effect in atherosclerosis, further in comparison with each other, we determined the effect of pharmacological doses of them upon the adhesion of THP-1 cells to human umbilical vein endothelial cells (HUVEC), as well as the expression of adhesion molecules, the translocation of NF-K B in HUVEC. Adhesion of THP-1 cells to HUVEC was evaluated by co-culture experiments using calcein-AM-labeled THP-1 cells. The expression of adhesion molecules was evaluated by ELISA, real time-PCR and Western blot; the translocation of NE- k B were determined by immunochemical staining assay. TNF-o was used to induce inflammatory responses in HUVEC. Our results showed that these three structurally related stilbenes also show anti-inflammatory vascular activity but with different potency. TMS appears to be more potent than RSV for treating vascular inflammation, while PD is significantly less active than both of them. The mechanism of these anti-inflammatory effects may be mainly attributed to the inhibition of NF- B pathway activation. These results implied that all the three investigated stilbene compounds, especially TMS exhibited potent inhibitory effect on inflammation induced cell-cell adhesion and expression of adhesion molecules, and activation of NF-k B pathway. Therefore, it could be potentially developed as an alternative in the prevention and treatment of chronic inflammatory diseases such as atherosclerosis.

動脈粥樣硬化 (Atherosclerosis，As）是缺血性心股血管疾病的病理生理基 礎，是很多發達國家心腦血管疾病發生率和死亡率最高的主要原因，目前被認烏 是一種血管炎症性疾病。大量研究已經表明在炎症過程的發展中最爲重要、最開 始的一個事件就是單核-内皮細胞之間的黏附及遷移。在道一過程中，內皮細胞的活化及炎症部位黏附分子的表達是具有特殊意義的。因此，阻斷這些分子的表達將成爲治療急性、慢性炎症性疾病的一個重要靶標。二苯乙烯類化合物，自1940年首次從毛藜蘆根中分離出白藜蘆醇以來就對此 進行了廣泛研究。這類化合物存在於許多植物中並具有廣泛的生理活性，主要有 抗氧化、抗腫瘤、抗淤血綜合征（如腦炎、動脈粥樣硬化、慢性炎症）等。白藜 蘆醇 (trans-3,5,4-trihydroxystilbene)，是從中藥虎杖中提取出來的一種二苯乙烯 類化合物同時也是一種非常重要的植物内毒素，在近年來的實驗研究中已充分證 明其具有很多有益的藥理作用，如抗癌、心血管保護、神經保護、抗衰老和抗炎 等等。大量研究證實其在抗動脈粥樣硬化中起著非常重要的作用。近年來随著白 藜蘆醇的類似物的不斷出現，研究者們發現其中一些二苯乙烯類化合物同樣具有 許多與白藜蘆醇相似的藥理活性且某此化合物的活性、選擇性及穩定性均要強于 白藜蘆醇，故成爲目前研究的熱點。爲了探討白藜蘆醇類似物中甲基化白藜蘆醇 和白藜蘆醇苷的抗炎效應並闡明其作用機制，同時與白藜蘆醇進行比較，我們首 先用細胞黏附實驗測定其是否具有抗細胞黏附的能力，然後對其相關的黏附分子 的表達及NF-K B進行考察。黏附分子的表達用酶聯免疫吸附試驗、實時定量PCR 和Westemn blot方法進行測定，NF-1 B核轉位用免疫螢光染色技術進行測定。本 實驗用TNF-a導HUVEC造成細胞炎症損傷，觀察這3種結構相似的二苯乙烯頻化合物的抗炎效應。我們的實驗結果表明白藜蘆醇及其類似物均具有抗炎效應，並且TMS作用效果是這3種化合物中最強的，而且該作用與NF-K B是否被活化相關：白藜蘆醇苷相對前二者作用要弱。這些結果提示TMS可能成爲預防和治療動脈粥樣硬化等慢性炎症性疾病的另一個有效的替代藥物。