| 摘要: | 本研究首先以醋酸扭體法及福馬林疼痛試驗法探討車前草70%乙醇粗抽物及其活性成分熊果酸之鎮痛作用，並以λ-角叉菜膠誘導小鼠足蹠腫脹探討其抗發炎作用，並測定小鼠肝組織之超氧歧化酶、麩胱甘肽還原酶、麩胱甘肽過氧化酶活性；及小鼠發炎足蹠組織中丙二醛的含量、一氧化氮濃度及環氧化酶活性；血清中白介素-1β與腫瘤壞死因子之含量變化來探討車前草70%乙醇粗抽物及其成分熊果酸是否藉由提升抗氧化酵素活性及抑制發炎性介質之含量而達到抗發炎作用。
結果發現，於鎮痛試驗中，車前草70%乙醇粗抽物（0.1, 0.5與1.0 g/kg）及熊果酸（10, 20與40 mg/kg）均可減少由醋酸所引起疼痛之扭體次數及福馬林引起之後期舔足反應時間。於抗發炎試驗中，車前草70%乙醇粗抽物（0.1, 0.5與1.0 g/kg）及熊果酸（10, 20與40 mg/kg），可明顯抑制λ- carrageenan誘導的急性足蹠腫脹。
於肝組織抗氧化酵素活性測定中，車前草70%乙醇粗抽物及熊果酸對肝臟中之超氧歧化酶（superoxide dismutase，SOD）、麩胱甘肽還原酶（glutathoine reductase，GR）及麩胱甘肽過氧化酶（glutathione peroxidase，GPx）活性均具增強作用並會減少小鼠發炎足蹠組織中丙二醛（malondialdehyde，MDA）及一氧化氮（nitric oxide，NO）的含量。且熊果酸亦會減少發炎後環氧化酶Ⅱ（Cyclooxygenase-2，COX-2）之活性以及血清中白介素-1β（Interleukin-1β，IL-1β）及腫瘤壞死因子（Tumor Necrosis Factor-α，TNF-α）的含量。
綜合上述結果顯示，車前草70%乙醇粗抽物及其活性成分熊果酸具有鎮痛、抗發炎作用。其鎮痛效果與周邊抑制花生四烯酸代謝，減少前列腺素合成有關；而抗發炎之作用機轉可能藉由提升肝臟中抗氧化酵素，而利於清除自由基；此外亦能抑制發炎足蹠組織中NO的含量，而減少脂質過氧化；且其活性成分熊果酸能抑制TNF-α及IL-1β的濃度及COX-2的活性，進而減少前列腺素的生成，而達到抗發炎的作用。
In the present study, the analgesic effect of 70% ethanol extract of Plantago asiatica LINNAEUS （PAEtOH）and ursolic acid, an active constitute of PAEtOH, in acetic acid-induced writhing response and formalin-induced paw licking test and the anti-inflammatory effect of PAEtOH and ursolic acid in λ-carrageenan-induced paw edema are investigated. In order to understand the anti-inflammatory mechanism of PAEtOH and ursolic acid, we evaluated superoxide dismutase（SOD）, glutathoine reductase（GR）, glutathione peroxidase（GPx）activities in liver and the levels of malondialdehyde（MDA）, nitric oxide（NO）and cyclooxygenase 2（COX-2）activity in the paw tissue, interleukin-1β（IL-1β）and tumor necrosis factor- α（TNF-α）levels in serum in mice are evaluated.
The results shown that PAEtOH （0.1, 0.5 and 1.0 g/kg）and ursolic acid （10, 20 and 40 mg/kg）, significantly decreased the acetic acid intraperitoneal injection induced writhing responses and formalin subplantar injection induced late phase of pain response and caused a significantly inhibition of the λ-carrageenan-induced paw edema in mice.
PAEtOH and ursolic acid also caused significant increase in SOD, GR and GPx activities and decrease in the MDA and NO levels in mice liver tissue. Ursolic acid selectively blocked COX-2 activity in the paw and significantly inhibited pro-inflammatory cytokines（IL-1β and TNF-α）, by λ-carrageenan induced in the serum in mice.
In conclusion, these results suggested that PAEtOH and ursolic acid were endowed with analgesic and anti-inflammatory effects. The analgesic effect may be due to inhibition of the synthesis of the arachidonic acid metabolite and decreases prostaglandins production. The anti-inflammatory mechanisms of PAEtOH and ursolic acid may be related to the increases in the activities of the anti-oxidant enzymes in the liver and the decreases in the MDA and NO production in the edema paw tissue via suppressing the pro-inflammatory cytokines（IL-1β and TNF-α）production and COX-2 activity. |
