Mechanisms Involved in the Anti-inflammatory Effect of a Standardized Willow Bark Extract
Mechanisms Involved in the Anti-inflammatory Effect of a Standardized Willow Bark Extract
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DOI：
10.1055/s-0031-1296917
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发表时间：
2005-11
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影响因子：
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通讯作者：
M. Khayyal;M. El-Ghazaly;D. Abdallah;S. Okpanyi;O. Kelber;D. Weiser
中科院分区：
文献类型：
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作者：
M. Khayyal;M. El-Ghazaly;D. Abdallah;S. Okpanyi;O. Kelber;D. Weiser
对标准柳树皮提取物（STW 33-I）进行了研究，以阐明其作为抗炎剂的可能机制。在两种炎症模型中进行了多方面的研究：代表急性状态的大鼠6天气囊模型和代表慢性状态的佐剂性关节炎。参数包括白细胞浸润，血液中细胞因子和前列腺素水平，对环加氧酶(COX)-1和/或COX-2酶的影响以及自由基产生的影响。在两种剂量水平下比较提取物的效果，其中乙酰水杨酸（CAS 50-78-2， ASA）作为非选择性COX-2抑制剂，塞来昔布（CAS 169590-42-5）作为选择性COX-2抑制剂的抗炎剂量相当。在mg/kg的基础上，提取物在减少炎症渗出和抑制白细胞浸润以及防止细胞因子上升方面至少与ASA一样有效，并且在抑制白三烯方面比ASA更有效，但在抑制前列腺素方面同样有效。在COX-2上，STW 33-I比ASA更有效。目前的研究结果表明，STW 33-I显著提高GSH（还原型谷胱甘肽）水平，这有助于限制脂质过氧化。该提取物比ASA或塞来昔布更有效。高剂量的提取物还能降低丙二醛水平，提高超氧化物歧化酶活性。综上所述，STW 33-I在保护机体抗氧化应激方面明显优于ASA或塞来昔布。因此，很明显，当两种炎症介质的剂量相同时，STW 33-I对所测炎症介质的所有参数的活性至少与ASA相同。然而，考虑到提取物仅含有24%的水杨苷（分子量286.2），而ASA的分子量为180.3，因此，在水杨苷与水杨酸盐的摩尔基础上，提取物中水杨苷的含量不到ASA中水杨酸盐含量的六分之一。因此，与同等剂量的ASA相比，STW 33-I的“水杨苷”含量较低，但在测量参数上至少与ASA一样具有活性，这一事实导致人们推测提取物的其他成分有助于其整体活性。STW 33-I中多酚的存在可能对增强其自由基清除能力起重要作用。STW 33-I在这方面优于ASA的事实表明，在重量比的基础上，该提取物可能比ASA具有更好的抗炎作用，副作用可能更小。
Summary A standardized willow bark extract (STW 33-I) has been examined to clarify its possible mechanism of action as an anti-inflammatory agent. Various facets have been investigated in two inflammation models: the 6-day air pouch model in rats, representing the acute state and the adjuvant induced arthritis representing the chronic one. Parameters included leukocytic infiltration, levels of cytokines and prostanoids in blood, and effects on cyclo-oxygenase (COX)-1 and/or COX-2 enzymes as well as effects involving free radical production. The effect of the extract was compared at two dose levels with comparable anti-inflammatory doses of acetylsalicylic acid (CAS 50-78-2, ASA) as a non-selective COX inhibitor, and celecoxib (CAS 169590-42-5) as a selective COX-2 inhibitor. On a mg/kg basis, the extract was at least as effective as ASA in reducing inflammatory exudates and in inhibiting leukocytic infiltration as well as in preventing the rise in cytokines, and was more effective than ASA in suppressing leukotrienes, but equally effective in suppressing prostaglandins. On COX-2, STW 33-I was more effective than ASA. The present findings show that STW 33-I significantly raises GSH (reduced glutathione) levels, an effect which helps to limit lipid peroxidation. The extract was more potent than either ASA or celecoxib. Higher doses of the extract also reduced malondialdehyde levels and raised superoxide dismutase activity. Taking the above results collectively, STW 33-I shows definite superiority to either ASA or celecoxib in protecting the body against oxidative stress. It is therefore evident that STW 33-I is at least as active as ASA on all the parameters of inflammatory mediators measured, when both are given on a similar mg/kg dose. Considering, however, that the extract contains only 24% salicin (molecular weight 286.2), while ASA has a molecular weight of 180.3, it follows that on a molar basis of salicin vs salicylate, the extract contains less than a sixth of the amount of salicin as the amount of salicylate in ASA. Thus it appears that STW 33-I with its lower “salicin” content than an equivalent dose of ASA, is at least as active as ASA on the measured parameters, a fact that leads one to speculate that other constituents of the extract contribute to its overall activity. The presence of polyphenols in STW 33-I probably plays a significant role in enhancing its free radical scavenging properties. The fact that STW 33-I was superior to ASA in this respect would suggest that the extract may have a better anti-inflammatory effect than ASA on a weight to weight basis, with possibly less side effects.